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Compound could treat a range of blood cancers
Image by Ed Uthman
A new compound has shown promise for treating hematologic malignancies and other cancers, according to preclinical research published in Nature.
The compound, known as S63845, targets the BCL2 family protein MCL1.
Investigators said their research on S63845 provides the first clear evidence that inhibiting MCL1 is effective in targeting several cancer types, including leukemia, lymphoma, and multiple myeloma (MM).
“MCL1 is important for many cancers because it is a pro-survival protein that allows the cancerous cells to evade the process of programmed cell death that normally removes cancer cells from the body,” said study author Guillaume Lessene, PhD, of the Walter and Eliza Hall Institute in Melbourne, Australia.
“Extensive studies performed in a variety of cancer models have shown that S63845 potently targets cancer cells dependent on MCL1 for their survival.”
About S63845
Dr Lessene and his colleagues said S63845 binds with high affinity to the BH3-binding groove of MCL1. And the compound kills MCL1-dependent cancer cells by activating the BAX/BAK-dependent mitochondrial apoptotic pathway.
In solid tumors, S63845 often wasn’t effective enough on its own. However, when the compound was combined with various kinase inhibitors, it induced a “potent cytotoxic response” in breast cancer, lung cancer, and melanoma cells.
In hematologic malignancies, S63845 proved effective when given alone.
Myeloma
The investigators said 17 of 25 MM cell lines tested were highly sensitive to S63845 (IC50 < 0.1 μ M), 6 cell lines were moderately sensitive (0.1 μ M < IC50 < 1 μ M), and 2 cell lines were insensitive (IC50 > 1 μ M).
The team also administered S63845 (at 25 mg/kg) to mice with MM. Seven of 8 mice had complete regression at 100 days after treatment.
Lymphoma
The investigators tested S63845 in 11 cell lines representative of human lymphomas. Five were highly sensitive to the compound (IC50 < 0.1 μ M), 3 were moderately sensitive (0.1 μ M < IC50 < 1 μ M), and 3 were insensitive (IC50 > 1 μ M).
The team also tested S63845 in 7 c-MYC-driven human Burkitt lymphoma cell lines and found the compound exhibited “potent cytotoxic activity” in all of them.
The investigators then tested S63845 in a c-MYC-driven mouse lymphoma model. They noted that both tumor cells and normal tissues express mouse MCL1 protein in this model.
Treatment with S63845 (25 mg/kg) for 5 consecutive days cured 70% of these mice, and the investigators said there were no evident side effects in normal tissues.
Leukemia
The investigators tested S63845 in 5 chronic myeloid leukemia cell lines, and none of them were sensitive to the compound.
However, the team also tested S63845 in 8 acute myeloid leukemia (AML) cell lines, and all of them were sensitive to the compound (IC50 4–233 nM).
When S63845 was given to mice with AML (25 mg/kg), 6 of the 8 mice achieved complete remission after 80 days.
The investigators also tested S63845 in 25 freshly derived samples from patients with AML. The team said these samples displayed a wide range of responses to S63845.
The most sensitive samples required 100- to 1000-fold less drug (to induce apoptosis) than the resistant samples or normal CD34+ progenitor cells.
Development/funding
S63845 was discovered through a collaboration between 2 pharmaceutical companies—Servier, which is headquartered in France, and Vernalis (R&D), which is based in the UK.
“[C]linical development of a MCL1 inhibitor should be launched in the near future,” said Olivier Geneste, director of oncology research at Servier.
The current research was supported through a collaboration with Servier and through funding from the National Health and Medical Research Council of Australia, the Leukemia and Lymphoma Society, Cancer Council Victoria, the Kay Kendall Leukemia Fund, Victorian Cancer Agency, Australian Cancer Research Foundation, the Victorian Government Operational Infrastructure Scheme, and the estate of Anthony Redstone. 
Image by Ed Uthman
A new compound has shown promise for treating hematologic malignancies and other cancers, according to preclinical research published in Nature.
The compound, known as S63845, targets the BCL2 family protein MCL1.
Investigators said their research on S63845 provides the first clear evidence that inhibiting MCL1 is effective in targeting several cancer types, including leukemia, lymphoma, and multiple myeloma (MM).
“MCL1 is important for many cancers because it is a pro-survival protein that allows the cancerous cells to evade the process of programmed cell death that normally removes cancer cells from the body,” said study author Guillaume Lessene, PhD, of the Walter and Eliza Hall Institute in Melbourne, Australia.
“Extensive studies performed in a variety of cancer models have shown that S63845 potently targets cancer cells dependent on MCL1 for their survival.”
About S63845
Dr Lessene and his colleagues said S63845 binds with high affinity to the BH3-binding groove of MCL1. And the compound kills MCL1-dependent cancer cells by activating the BAX/BAK-dependent mitochondrial apoptotic pathway.
In solid tumors, S63845 often wasn’t effective enough on its own. However, when the compound was combined with various kinase inhibitors, it induced a “potent cytotoxic response” in breast cancer, lung cancer, and melanoma cells.
In hematologic malignancies, S63845 proved effective when given alone.
Myeloma
The investigators said 17 of 25 MM cell lines tested were highly sensitive to S63845 (IC50 < 0.1 μ M), 6 cell lines were moderately sensitive (0.1 μ M < IC50 < 1 μ M), and 2 cell lines were insensitive (IC50 > 1 μ M).
The team also administered S63845 (at 25 mg/kg) to mice with MM. Seven of 8 mice had complete regression at 100 days after treatment.
Lymphoma
The investigators tested S63845 in 11 cell lines representative of human lymphomas. Five were highly sensitive to the compound (IC50 < 0.1 μ M), 3 were moderately sensitive (0.1 μ M < IC50 < 1 μ M), and 3 were insensitive (IC50 > 1 μ M).
The team also tested S63845 in 7 c-MYC-driven human Burkitt lymphoma cell lines and found the compound exhibited “potent cytotoxic activity” in all of them.
The investigators then tested S63845 in a c-MYC-driven mouse lymphoma model. They noted that both tumor cells and normal tissues express mouse MCL1 protein in this model.
Treatment with S63845 (25 mg/kg) for 5 consecutive days cured 70% of these mice, and the investigators said there were no evident side effects in normal tissues.
Leukemia
The investigators tested S63845 in 5 chronic myeloid leukemia cell lines, and none of them were sensitive to the compound.
However, the team also tested S63845 in 8 acute myeloid leukemia (AML) cell lines, and all of them were sensitive to the compound (IC50 4–233 nM).
When S63845 was given to mice with AML (25 mg/kg), 6 of the 8 mice achieved complete remission after 80 days.
The investigators also tested S63845 in 25 freshly derived samples from patients with AML. The team said these samples displayed a wide range of responses to S63845.
The most sensitive samples required 100- to 1000-fold less drug (to induce apoptosis) than the resistant samples or normal CD34+ progenitor cells.
Development/funding
S63845 was discovered through a collaboration between 2 pharmaceutical companies—Servier, which is headquartered in France, and Vernalis (R&D), which is based in the UK.
“[C]linical development of a MCL1 inhibitor should be launched in the near future,” said Olivier Geneste, director of oncology research at Servier.
The current research was supported through a collaboration with Servier and through funding from the National Health and Medical Research Council of Australia, the Leukemia and Lymphoma Society, Cancer Council Victoria, the Kay Kendall Leukemia Fund, Victorian Cancer Agency, Australian Cancer Research Foundation, the Victorian Government Operational Infrastructure Scheme, and the estate of Anthony Redstone.
Image by Ed Uthman
A new compound has shown promise for treating hematologic malignancies and other cancers, according to preclinical research published in Nature.
The compound, known as S63845, targets the BCL2 family protein MCL1.
Investigators said their research on S63845 provides the first clear evidence that inhibiting MCL1 is effective in targeting several cancer types, including leukemia, lymphoma, and multiple myeloma (MM).
“MCL1 is important for many cancers because it is a pro-survival protein that allows the cancerous cells to evade the process of programmed cell death that normally removes cancer cells from the body,” said study author Guillaume Lessene, PhD, of the Walter and Eliza Hall Institute in Melbourne, Australia.
“Extensive studies performed in a variety of cancer models have shown that S63845 potently targets cancer cells dependent on MCL1 for their survival.”
About S63845
Dr Lessene and his colleagues said S63845 binds with high affinity to the BH3-binding groove of MCL1. And the compound kills MCL1-dependent cancer cells by activating the BAX/BAK-dependent mitochondrial apoptotic pathway.
In solid tumors, S63845 often wasn’t effective enough on its own. However, when the compound was combined with various kinase inhibitors, it induced a “potent cytotoxic response” in breast cancer, lung cancer, and melanoma cells.
In hematologic malignancies, S63845 proved effective when given alone.
Myeloma
The investigators said 17 of 25 MM cell lines tested were highly sensitive to S63845 (IC50 < 0.1 μ M), 6 cell lines were moderately sensitive (0.1 μ M < IC50 < 1 μ M), and 2 cell lines were insensitive (IC50 > 1 μ M).
The team also administered S63845 (at 25 mg/kg) to mice with MM. Seven of 8 mice had complete regression at 100 days after treatment.
Lymphoma
The investigators tested S63845 in 11 cell lines representative of human lymphomas. Five were highly sensitive to the compound (IC50 < 0.1 μ M), 3 were moderately sensitive (0.1 μ M < IC50 < 1 μ M), and 3 were insensitive (IC50 > 1 μ M).
The team also tested S63845 in 7 c-MYC-driven human Burkitt lymphoma cell lines and found the compound exhibited “potent cytotoxic activity” in all of them.
The investigators then tested S63845 in a c-MYC-driven mouse lymphoma model. They noted that both tumor cells and normal tissues express mouse MCL1 protein in this model.
Treatment with S63845 (25 mg/kg) for 5 consecutive days cured 70% of these mice, and the investigators said there were no evident side effects in normal tissues.
Leukemia
The investigators tested S63845 in 5 chronic myeloid leukemia cell lines, and none of them were sensitive to the compound.
However, the team also tested S63845 in 8 acute myeloid leukemia (AML) cell lines, and all of them were sensitive to the compound (IC50 4–233 nM).
When S63845 was given to mice with AML (25 mg/kg), 6 of the 8 mice achieved complete remission after 80 days.
The investigators also tested S63845 in 25 freshly derived samples from patients with AML. The team said these samples displayed a wide range of responses to S63845.
The most sensitive samples required 100- to 1000-fold less drug (to induce apoptosis) than the resistant samples or normal CD34+ progenitor cells.
Development/funding
S63845 was discovered through a collaboration between 2 pharmaceutical companies—Servier, which is headquartered in France, and Vernalis (R&D), which is based in the UK.
“[C]linical development of a MCL1 inhibitor should be launched in the near future,” said Olivier Geneste, director of oncology research at Servier.
The current research was supported through a collaboration with Servier and through funding from the National Health and Medical Research Council of Australia, the Leukemia and Lymphoma Society, Cancer Council Victoria, the Kay Kendall Leukemia Fund, Victorian Cancer Agency, Australian Cancer Research Foundation, the Victorian Government Operational Infrastructure Scheme, and the estate of Anthony Redstone.
Serious AEs reported too late in lymphoma trial
Photo by Bill Branson
Investigators conducting a phase 1 trial failed to follow requirements for reporting serious adverse events (AEs), including deaths, according to officials from the National Cancer Institute (NCI) and the National Institutes of Health (NIH).
The trial was an NCI-sponsored study of ibrutinib in combination with dose-adjusted temozolomide, etoposide, liposomal doxorubicin, dexamethasone, and rituximab (DA-TEDDi-R) in patients with primary CNS lymphoma.
Four patients in this trial developed invasive aspergillosis, 3 others had unconfirmed Aspergillus infections, and 2 patients died of aspergillosis in 2015.
Trial investigators did not report these events to the NCI or the institutional review board (IRB) as quickly as required by the study protocol.
In addition, the suspected relationship between Aspergillus infections and the study treatment wasn’t reported to the US Food and Drug Administration (FDA) until May 2016, several months after the second patient died of aspergillosis.
Francis S. Collins, MD, PhD, director of the NIH, and Douglas R. Lowy, MD, acting director of the NCI, discussed this delay in reporting during a meeting of the Clinical Center Hospital Board last Friday.
About the trial
The trial (NCT02203526) enrolled 18 patients with primary CNS lymphoma—13 relapsed/refractory and 5 previously untreated—between August 2014 and March 2016.
Patients received 14 days of ibrutinib (with corticosteroids to prevent cerebral edema), followed by six 21-day cycles of DA-TEDDi-R.
Twelve patients achieved a complete response following treatment, 5 had a partial response, and 1 patient progressed without responding. Eight patients remain in complete response, 2 have progressed, and 8 have died.
Four patients developed invasive aspergillosis, and 3 had possible Aspergillus infections. Two deaths, which occurred in May and December of 2015, were attributed to aspergillosis.
Some patients developed aspergillosis while they were receiving only steroids and ibrutinib, which led the investigators to believe there was a causative relationship between Aspergillus infections and treatment with ibrutinib/steroids.
The investigators stopped trial accrual in April 2016 due to the Aspergillus infections. The suspected relationship between the infections and ibrutinib/steroids was reported to the FDA in late May 2016.
Delayed reporting
On October 3, 2016, the FDA issued a 483 report to the trial’s principal investigator, Kieron Dunleavy, MD, of the NCI. The report cited “delays and deficient reporting” of serious AEs/unanticipated problems to the trial’s sponsor and IRB.
The trial’s protocol required that grade 3-5 AEs be reported to the NCI within 24 hours of occurrence and unanticipated problems be reported to the IRB within 7 days.
The median time of delayed reporting to the NCI was 40 days (range, 4 to 456), and the median time of delayed reporting to the IRB was 18 days (range, 8 to 56).
As a result of the delayed reporting, Dr Dunleavy has been suspended from conducting clinical research in the NIH Clinical Center, and holds have been placed on trials conducted by the NCI lymphoma team.
The accrual of current studies and the opening of planned studies by the lymphoma team have been stopped. The team will be allowed to resume/begin studies after they undergo training and once the NCI and an outside contractor complete an audit of all NCI lymphoma trials that have been open over the last 3 years.
Patients involved in the trial of DA-TEDDi-R (and their families) have been informed of the delayed AE reporting.
Various parties involved in NIH/NCI trials have been reminded about the importance of timely reporting of safety and regulatory information.
The NCI and NIH are taking steps to ensure that AEs are reported promptly in the future. And the Office of Research Support and Compliance has been tasked with investigating past reporting of AEs in NIH trials, particularly those conducted at the Clinical Center.
Photo by Bill Branson
Investigators conducting a phase 1 trial failed to follow requirements for reporting serious adverse events (AEs), including deaths, according to officials from the National Cancer Institute (NCI) and the National Institutes of Health (NIH).
The trial was an NCI-sponsored study of ibrutinib in combination with dose-adjusted temozolomide, etoposide, liposomal doxorubicin, dexamethasone, and rituximab (DA-TEDDi-R) in patients with primary CNS lymphoma.
Four patients in this trial developed invasive aspergillosis, 3 others had unconfirmed Aspergillus infections, and 2 patients died of aspergillosis in 2015.
Trial investigators did not report these events to the NCI or the institutional review board (IRB) as quickly as required by the study protocol.
In addition, the suspected relationship between Aspergillus infections and the study treatment wasn’t reported to the US Food and Drug Administration (FDA) until May 2016, several months after the second patient died of aspergillosis.
Francis S. Collins, MD, PhD, director of the NIH, and Douglas R. Lowy, MD, acting director of the NCI, discussed this delay in reporting during a meeting of the Clinical Center Hospital Board last Friday.
About the trial
The trial (NCT02203526) enrolled 18 patients with primary CNS lymphoma—13 relapsed/refractory and 5 previously untreated—between August 2014 and March 2016.
Patients received 14 days of ibrutinib (with corticosteroids to prevent cerebral edema), followed by six 21-day cycles of DA-TEDDi-R.
Twelve patients achieved a complete response following treatment, 5 had a partial response, and 1 patient progressed without responding. Eight patients remain in complete response, 2 have progressed, and 8 have died.
Four patients developed invasive aspergillosis, and 3 had possible Aspergillus infections. Two deaths, which occurred in May and December of 2015, were attributed to aspergillosis.
Some patients developed aspergillosis while they were receiving only steroids and ibrutinib, which led the investigators to believe there was a causative relationship between Aspergillus infections and treatment with ibrutinib/steroids.
The investigators stopped trial accrual in April 2016 due to the Aspergillus infections. The suspected relationship between the infections and ibrutinib/steroids was reported to the FDA in late May 2016.
Delayed reporting
On October 3, 2016, the FDA issued a 483 report to the trial’s principal investigator, Kieron Dunleavy, MD, of the NCI. The report cited “delays and deficient reporting” of serious AEs/unanticipated problems to the trial’s sponsor and IRB.
The trial’s protocol required that grade 3-5 AEs be reported to the NCI within 24 hours of occurrence and unanticipated problems be reported to the IRB within 7 days.
The median time of delayed reporting to the NCI was 40 days (range, 4 to 456), and the median time of delayed reporting to the IRB was 18 days (range, 8 to 56).
As a result of the delayed reporting, Dr Dunleavy has been suspended from conducting clinical research in the NIH Clinical Center, and holds have been placed on trials conducted by the NCI lymphoma team.
The accrual of current studies and the opening of planned studies by the lymphoma team have been stopped. The team will be allowed to resume/begin studies after they undergo training and once the NCI and an outside contractor complete an audit of all NCI lymphoma trials that have been open over the last 3 years.
Patients involved in the trial of DA-TEDDi-R (and their families) have been informed of the delayed AE reporting.
Various parties involved in NIH/NCI trials have been reminded about the importance of timely reporting of safety and regulatory information.
The NCI and NIH are taking steps to ensure that AEs are reported promptly in the future. And the Office of Research Support and Compliance has been tasked with investigating past reporting of AEs in NIH trials, particularly those conducted at the Clinical Center.
Photo by Bill Branson
Investigators conducting a phase 1 trial failed to follow requirements for reporting serious adverse events (AEs), including deaths, according to officials from the National Cancer Institute (NCI) and the National Institutes of Health (NIH).
The trial was an NCI-sponsored study of ibrutinib in combination with dose-adjusted temozolomide, etoposide, liposomal doxorubicin, dexamethasone, and rituximab (DA-TEDDi-R) in patients with primary CNS lymphoma.
Four patients in this trial developed invasive aspergillosis, 3 others had unconfirmed Aspergillus infections, and 2 patients died of aspergillosis in 2015.
Trial investigators did not report these events to the NCI or the institutional review board (IRB) as quickly as required by the study protocol.
In addition, the suspected relationship between Aspergillus infections and the study treatment wasn’t reported to the US Food and Drug Administration (FDA) until May 2016, several months after the second patient died of aspergillosis.
Francis S. Collins, MD, PhD, director of the NIH, and Douglas R. Lowy, MD, acting director of the NCI, discussed this delay in reporting during a meeting of the Clinical Center Hospital Board last Friday.
About the trial
The trial (NCT02203526) enrolled 18 patients with primary CNS lymphoma—13 relapsed/refractory and 5 previously untreated—between August 2014 and March 2016.
Patients received 14 days of ibrutinib (with corticosteroids to prevent cerebral edema), followed by six 21-day cycles of DA-TEDDi-R.
Twelve patients achieved a complete response following treatment, 5 had a partial response, and 1 patient progressed without responding. Eight patients remain in complete response, 2 have progressed, and 8 have died.
Four patients developed invasive aspergillosis, and 3 had possible Aspergillus infections. Two deaths, which occurred in May and December of 2015, were attributed to aspergillosis.
Some patients developed aspergillosis while they were receiving only steroids and ibrutinib, which led the investigators to believe there was a causative relationship between Aspergillus infections and treatment with ibrutinib/steroids.
The investigators stopped trial accrual in April 2016 due to the Aspergillus infections. The suspected relationship between the infections and ibrutinib/steroids was reported to the FDA in late May 2016.
Delayed reporting
On October 3, 2016, the FDA issued a 483 report to the trial’s principal investigator, Kieron Dunleavy, MD, of the NCI. The report cited “delays and deficient reporting” of serious AEs/unanticipated problems to the trial’s sponsor and IRB.
The trial’s protocol required that grade 3-5 AEs be reported to the NCI within 24 hours of occurrence and unanticipated problems be reported to the IRB within 7 days.
The median time of delayed reporting to the NCI was 40 days (range, 4 to 456), and the median time of delayed reporting to the IRB was 18 days (range, 8 to 56).
As a result of the delayed reporting, Dr Dunleavy has been suspended from conducting clinical research in the NIH Clinical Center, and holds have been placed on trials conducted by the NCI lymphoma team.
The accrual of current studies and the opening of planned studies by the lymphoma team have been stopped. The team will be allowed to resume/begin studies after they undergo training and once the NCI and an outside contractor complete an audit of all NCI lymphoma trials that have been open over the last 3 years.
Patients involved in the trial of DA-TEDDi-R (and their families) have been informed of the delayed AE reporting.
Various parties involved in NIH/NCI trials have been reminded about the importance of timely reporting of safety and regulatory information.
The NCI and NIH are taking steps to ensure that AEs are reported promptly in the future. And the Office of Research Support and Compliance has been tasked with investigating past reporting of AEs in NIH trials, particularly those conducted at the Clinical Center.
Legislators question price of leukemia drug
Photo from Business Wire
A pair of US legislators are questioning why ARIAD Pharmaceuticals, Inc. has increased the price of its leukemia drug Iclusig (ponatinib) by more than $80,000 over the last several years.
ARIAD raised the price of Iclusig 4 times in 2016. The drug now costs nearly $199,000 a year.
Senator Bernie Sanders (Vermont) and Congressman Elijah Cummings (Maryland) sent a letter to ARIAD last week requesting information about these price increases.
Cummings and Sanders are also investigating whether ARIAD took additional steps to boost profits by discontinuing sales of certain dosages and quantities of Iclusig in order to charge patients and insurers more in exchange for less medicine.
“These outrageous sales tactics indicate that ARIAD is more concerned with its profit than with its patients,” Sanders and Cummings wrote in the letter.
The US Food and Drug Administration (FDA) approved Iclusig in December 2012 to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).
In late 2013, the FDA suspended sales and clinical trials of the drug due to reports of serious adverse events.
The FDA allowed ARIAD to resume selling Iclusig in December 2013, but only to CML/ALL patients who cannot tolerate, or whose disease is resistant to, other tyrosine kinase inhibitors.
“Despite this new evidence showing the drug posed a far greater safety risk to patients than was known when the drug came on the market, ARIAD nonetheless raised the price of Iclusig several times over the subsequent 4 years,” Sanders and Cummings wrote.
“In the interest of patients and taxpayers, we are interested in learning more about the impact that the escalating price and restrictions on product availability have had.”
ARIAD has released a statement acknowledging Cummings’ and Sanders’ letter and defending its decisions to increase the price of Iclusig.
The company said it “makes significant investments in research and development (R&D) to advance breakthrough treatments” for patients with rare cancers.
In fact, ARIAD has invested more than $1.3 billion in R&D and accumulated losses of approximately $1.4 billion, which have not been recovered. In 2015, ARIAD generated $119 million in total revenue and invested $171 million in R&D.
The company said it intends to respond to Cummings’ and Sanders’ request for information.
Photo from Business Wire
A pair of US legislators are questioning why ARIAD Pharmaceuticals, Inc. has increased the price of its leukemia drug Iclusig (ponatinib) by more than $80,000 over the last several years.
ARIAD raised the price of Iclusig 4 times in 2016. The drug now costs nearly $199,000 a year.
Senator Bernie Sanders (Vermont) and Congressman Elijah Cummings (Maryland) sent a letter to ARIAD last week requesting information about these price increases.
Cummings and Sanders are also investigating whether ARIAD took additional steps to boost profits by discontinuing sales of certain dosages and quantities of Iclusig in order to charge patients and insurers more in exchange for less medicine.
“These outrageous sales tactics indicate that ARIAD is more concerned with its profit than with its patients,” Sanders and Cummings wrote in the letter.
The US Food and Drug Administration (FDA) approved Iclusig in December 2012 to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).
In late 2013, the FDA suspended sales and clinical trials of the drug due to reports of serious adverse events.
The FDA allowed ARIAD to resume selling Iclusig in December 2013, but only to CML/ALL patients who cannot tolerate, or whose disease is resistant to, other tyrosine kinase inhibitors.
“Despite this new evidence showing the drug posed a far greater safety risk to patients than was known when the drug came on the market, ARIAD nonetheless raised the price of Iclusig several times over the subsequent 4 years,” Sanders and Cummings wrote.
“In the interest of patients and taxpayers, we are interested in learning more about the impact that the escalating price and restrictions on product availability have had.”
ARIAD has released a statement acknowledging Cummings’ and Sanders’ letter and defending its decisions to increase the price of Iclusig.
The company said it “makes significant investments in research and development (R&D) to advance breakthrough treatments” for patients with rare cancers.
In fact, ARIAD has invested more than $1.3 billion in R&D and accumulated losses of approximately $1.4 billion, which have not been recovered. In 2015, ARIAD generated $119 million in total revenue and invested $171 million in R&D.
The company said it intends to respond to Cummings’ and Sanders’ request for information.
Photo from Business Wire
A pair of US legislators are questioning why ARIAD Pharmaceuticals, Inc. has increased the price of its leukemia drug Iclusig (ponatinib) by more than $80,000 over the last several years.
ARIAD raised the price of Iclusig 4 times in 2016. The drug now costs nearly $199,000 a year.
Senator Bernie Sanders (Vermont) and Congressman Elijah Cummings (Maryland) sent a letter to ARIAD last week requesting information about these price increases.
Cummings and Sanders are also investigating whether ARIAD took additional steps to boost profits by discontinuing sales of certain dosages and quantities of Iclusig in order to charge patients and insurers more in exchange for less medicine.
“These outrageous sales tactics indicate that ARIAD is more concerned with its profit than with its patients,” Sanders and Cummings wrote in the letter.
The US Food and Drug Administration (FDA) approved Iclusig in December 2012 to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).
In late 2013, the FDA suspended sales and clinical trials of the drug due to reports of serious adverse events.
The FDA allowed ARIAD to resume selling Iclusig in December 2013, but only to CML/ALL patients who cannot tolerate, or whose disease is resistant to, other tyrosine kinase inhibitors.
“Despite this new evidence showing the drug posed a far greater safety risk to patients than was known when the drug came on the market, ARIAD nonetheless raised the price of Iclusig several times over the subsequent 4 years,” Sanders and Cummings wrote.
“In the interest of patients and taxpayers, we are interested in learning more about the impact that the escalating price and restrictions on product availability have had.”
ARIAD has released a statement acknowledging Cummings’ and Sanders’ letter and defending its decisions to increase the price of Iclusig.
The company said it “makes significant investments in research and development (R&D) to advance breakthrough treatments” for patients with rare cancers.
In fact, ARIAD has invested more than $1.3 billion in R&D and accumulated losses of approximately $1.4 billion, which have not been recovered. In 2015, ARIAD generated $119 million in total revenue and invested $171 million in R&D.
The company said it intends to respond to Cummings’ and Sanders’ request for information.
FDA grants drug orphan designation for GVHD
Photo by Linda Bartlett
The US Food and Drug Administration (FDA) has granted orphan drug designation to ALXN1007 for the treatment of acute graft-versus-host disease (GVHD).
ALXN1007 is an anti-inflammatory monoclonal antibody targeting complement protein C5a.
The drug is being developed
by Alexion Pharmaceuticals, Inc.
It is currently under investigation in a phase 2 trial of patients with acute GVHD of the lower gastrointestinal tract (GI-GVHD).
Results from this trial were presented at the 21st Congress of the European Hematology Association (abstract LB2269).
The presentation included 15 patients with newly diagnosed, biopsy-confirmed acute GI-GVHD. The patients had a median age of 60 (range, 25-69), and 60% were male.
Patients had acute myeloid leukemia/myelodysplastic syndrome (n=8), acute lymphoblastic leukemia (n=2), acute lymphocytic leukemia (n=1), acute myeloblastic leukemia (n=1), aplastic anemia (n=1), cutaneous T-cell lymphoma (n=1), and mantle cell lymphoma (n=1).
Most patients received transplants from matched, unrelated donors (n=11); 3 had matched, related donors; and 1 had a mismatched donor. Ten patients received peripheral blood grafts, 4 received cord blood, and 1 received a bone marrow transplant.
Patients had grade 1 (n=7), grade 2 (n=2), and grade 3 (n=6) acute GI-GVHD.
The patients received weekly doses of ALXN1007 at 10 mg/kg, in combination with methylprednisolone at an initial dose of 2 mg/kg, through day 56.
Thirteen patients were evaluable for efficacy. One patient experienced leukemia relapse at day 18, and 1 withdrew from the study early.
The overall acute GVHD response rate was 77% (10/13), both at day 28 and day 56. The complete GI-GVHD response rate was 69% at day 28 and 77% at day 56.
At day 180, the nonrelapse mortality rate was 12.5%, and the overall survival rate was 69.2%.
All of the patients had treatment-emergent adverse events (AEs), and 11 patients (69%) had serious treatment-emergent AEs.
Five patients experienced a total of 12 treatment-related AEs (1 case each)—adenovirus infection, bronchopulmonary aspergillosis, chills, corona virus infection, viral cystitis, Epstein-Barr virus infection, hypersensitivity, influenza, influenza-like illness, infusion-related reaction, respiratory syncytial virus infection, and tremor.
There were 6 deaths, but none were considered treatment-related.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
ALXN1007 has orphan designation from the European Commission as well.
Photo by Linda Bartlett
The US Food and Drug Administration (FDA) has granted orphan drug designation to ALXN1007 for the treatment of acute graft-versus-host disease (GVHD).
ALXN1007 is an anti-inflammatory monoclonal antibody targeting complement protein C5a.
The drug is being developed
by Alexion Pharmaceuticals, Inc.
It is currently under investigation in a phase 2 trial of patients with acute GVHD of the lower gastrointestinal tract (GI-GVHD).
Results from this trial were presented at the 21st Congress of the European Hematology Association (abstract LB2269).
The presentation included 15 patients with newly diagnosed, biopsy-confirmed acute GI-GVHD. The patients had a median age of 60 (range, 25-69), and 60% were male.
Patients had acute myeloid leukemia/myelodysplastic syndrome (n=8), acute lymphoblastic leukemia (n=2), acute lymphocytic leukemia (n=1), acute myeloblastic leukemia (n=1), aplastic anemia (n=1), cutaneous T-cell lymphoma (n=1), and mantle cell lymphoma (n=1).
Most patients received transplants from matched, unrelated donors (n=11); 3 had matched, related donors; and 1 had a mismatched donor. Ten patients received peripheral blood grafts, 4 received cord blood, and 1 received a bone marrow transplant.
Patients had grade 1 (n=7), grade 2 (n=2), and grade 3 (n=6) acute GI-GVHD.
The patients received weekly doses of ALXN1007 at 10 mg/kg, in combination with methylprednisolone at an initial dose of 2 mg/kg, through day 56.
Thirteen patients were evaluable for efficacy. One patient experienced leukemia relapse at day 18, and 1 withdrew from the study early.
The overall acute GVHD response rate was 77% (10/13), both at day 28 and day 56. The complete GI-GVHD response rate was 69% at day 28 and 77% at day 56.
At day 180, the nonrelapse mortality rate was 12.5%, and the overall survival rate was 69.2%.
All of the patients had treatment-emergent adverse events (AEs), and 11 patients (69%) had serious treatment-emergent AEs.
Five patients experienced a total of 12 treatment-related AEs (1 case each)—adenovirus infection, bronchopulmonary aspergillosis, chills, corona virus infection, viral cystitis, Epstein-Barr virus infection, hypersensitivity, influenza, influenza-like illness, infusion-related reaction, respiratory syncytial virus infection, and tremor.
There were 6 deaths, but none were considered treatment-related.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
ALXN1007 has orphan designation from the European Commission as well.
Photo by Linda Bartlett
The US Food and Drug Administration (FDA) has granted orphan drug designation to ALXN1007 for the treatment of acute graft-versus-host disease (GVHD).
ALXN1007 is an anti-inflammatory monoclonal antibody targeting complement protein C5a.
The drug is being developed
by Alexion Pharmaceuticals, Inc.
It is currently under investigation in a phase 2 trial of patients with acute GVHD of the lower gastrointestinal tract (GI-GVHD).
Results from this trial were presented at the 21st Congress of the European Hematology Association (abstract LB2269).
The presentation included 15 patients with newly diagnosed, biopsy-confirmed acute GI-GVHD. The patients had a median age of 60 (range, 25-69), and 60% were male.
Patients had acute myeloid leukemia/myelodysplastic syndrome (n=8), acute lymphoblastic leukemia (n=2), acute lymphocytic leukemia (n=1), acute myeloblastic leukemia (n=1), aplastic anemia (n=1), cutaneous T-cell lymphoma (n=1), and mantle cell lymphoma (n=1).
Most patients received transplants from matched, unrelated donors (n=11); 3 had matched, related donors; and 1 had a mismatched donor. Ten patients received peripheral blood grafts, 4 received cord blood, and 1 received a bone marrow transplant.
Patients had grade 1 (n=7), grade 2 (n=2), and grade 3 (n=6) acute GI-GVHD.
The patients received weekly doses of ALXN1007 at 10 mg/kg, in combination with methylprednisolone at an initial dose of 2 mg/kg, through day 56.
Thirteen patients were evaluable for efficacy. One patient experienced leukemia relapse at day 18, and 1 withdrew from the study early.
The overall acute GVHD response rate was 77% (10/13), both at day 28 and day 56. The complete GI-GVHD response rate was 69% at day 28 and 77% at day 56.
At day 180, the nonrelapse mortality rate was 12.5%, and the overall survival rate was 69.2%.
All of the patients had treatment-emergent adverse events (AEs), and 11 patients (69%) had serious treatment-emergent AEs.
Five patients experienced a total of 12 treatment-related AEs (1 case each)—adenovirus infection, bronchopulmonary aspergillosis, chills, corona virus infection, viral cystitis, Epstein-Barr virus infection, hypersensitivity, influenza, influenza-like illness, infusion-related reaction, respiratory syncytial virus infection, and tremor.
There were 6 deaths, but none were considered treatment-related.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
ALXN1007 has orphan designation from the European Commission as well.
Speaker says use the best regimen ASAP in MM
NEW YORK—It’s important to use the best possible regimen as soon as possible when treating patients with multiple myeloma (MM), according to a speaker at Lymphoma & Myeloma 2016.
Antonio Palumbo, MD, of the University of Torino in Italy, explained that the urgency, from a biological point of view, is because myeloma accumulates genetic mutations that change the disease in a “dramatic way.”
“At diagnosis, you might have 5000 mutations, and, at first relapse, there are 12,000 mutations,” he said. “They are completely different tumors. So the first thing that we have to recognize is that, with time, myeloma is not the same. It’s becoming different tumors.”
Dr Palumbo noted that early intervention is important because genetic and epigenetic abnormalities increase as the disease progresses and becomes more resistant.
For example, if 100 patients receive first-line treatment, 40 of them will not reach the second line. Only 60 patients will receive second-line therapy, and only 35 patients will receive third-line treatment. By the fifth line, only 10 patients, or 10%, will receive it.
“If you have very good genomic stability, you can become sensitive to different treatments,” Dr Palumbo said. “But if you become a different disease, you will not be able to receive the next therapy. That’s why it’s so important . . . to use the best possible regimen as soon as possible.”
Best regimens
The triplet bortezomib-lenalidomide-dexamethasone is the “best possible regimen today,” Dr Palumbo said, “followed by continuous therapy.”
The 2-drug combination of lenalidomide and dexamethasone is probably more suitable for the elderly and the frail.
Alternative regimens include carfilzomib-cyclophosphamide-dexamethasone and ixazomib-lenalidomide-dexamethasone.
Continuous therapy
Continuous therapy has been “one of the major achievements” in the treatment of MM, Dr Palumbo said. Without continuous therapy, patients in complete response remain so for about 1 year when treated with conventional chemotherapy.
Investigators found that maintenance therapy significantly prolongs progression-free survival and overall survival (P=0.02). They recommend intensification with maintenance to optimize treatment efficacy and prolong survival.
Immunomodulatory drugs such as lenalidomide are the backbone of continuous therapy today.
However, ixazomib represents another option. Ixazomib maintenance has been shown to produce durable responses for a median of more than 2 years in previously untreated patients not undergoing autologous stem cell transplant.
Salvage therapy
Seven combinations are now available for salvage therapy, including those with proteasome inhibitors, monoclonal antibodies, pomalidomide, and histone deacetylase inhibitors.
Included in some of these combinations are the newer agents ixazomib, elotuzumab, and daratumumab, “which many might consider the new rituximab,” Dr Palumbo said.
Risk stratification
Dr Palumbo stressed the importance of risk stratification—both in clinical trials and in practice.
“[T]he moment you under-treat a patient, you transform a good-risk patient into a high-risk patient . . . ,” he said.
And if trials comparing treatments are not conducted within risk categories, researchers are comparing apples to oranges—good risk with high risk
The Revised International Staging System (R-ISS) for MM effectively stratifies newly diagnosed patients by combining the original ISS, chromosomal abnormalities, and serum lactate dehydrogenase levels to evaluate prognosis.
The R-ISS defines 3 new, distinct categories that researchers believe effectively define patients’ relative risk with respect to their survival.
Age and frailty
MM patients generally fall into 3 age categories: 25-64, 65-74, and 75-101.
The youngest group can receive autologous transplant, the fit patients ages 65 to 74 can receive full-dose chemotherapy, and the oldest, frailer patients should receive reduced-dose chemotherapy.
“It’s important to differentiate fit from frail,” Dr Palumbo said, “because we cannot give the same treatment schema to a 55-year-old versus 65 or 85. At 85, that schema would create a lot of toxicities.”
In frail patients, it’s always important to check which comorbidities are present using the Charlson comorbidity scale, Dr Palumbo said.
“Remember, when we put together age, chromosome abnormalities, and frailty, frailty is the most relevant prognostic factor when you add everything together,” he said.
“Two drugs versus 3 drugs doesn’t make much difference when you are starting to introduce treatment to these very frail patients with comorbidities.”
Minimal residual disease
Dr Palumbo indicated that a combination of MRI and PET-CT should be used for a more accurate indication of minimal residual disease.
“[W]e hope to have cure, [but] I don’t think, today, myeloma is a curable disease,” he said.
He clarified this by saying that patients who are in complete response and minimal residual disease-negative at 3 years do well, but, by 7 years, “something is happening.”
And at 10 years, progression-free survival has dropped off significantly, “telling us that cure is probably not yet there.”
NEW YORK—It’s important to use the best possible regimen as soon as possible when treating patients with multiple myeloma (MM), according to a speaker at Lymphoma & Myeloma 2016.
Antonio Palumbo, MD, of the University of Torino in Italy, explained that the urgency, from a biological point of view, is because myeloma accumulates genetic mutations that change the disease in a “dramatic way.”
“At diagnosis, you might have 5000 mutations, and, at first relapse, there are 12,000 mutations,” he said. “They are completely different tumors. So the first thing that we have to recognize is that, with time, myeloma is not the same. It’s becoming different tumors.”
Dr Palumbo noted that early intervention is important because genetic and epigenetic abnormalities increase as the disease progresses and becomes more resistant.
For example, if 100 patients receive first-line treatment, 40 of them will not reach the second line. Only 60 patients will receive second-line therapy, and only 35 patients will receive third-line treatment. By the fifth line, only 10 patients, or 10%, will receive it.
“If you have very good genomic stability, you can become sensitive to different treatments,” Dr Palumbo said. “But if you become a different disease, you will not be able to receive the next therapy. That’s why it’s so important . . . to use the best possible regimen as soon as possible.”
Best regimens
The triplet bortezomib-lenalidomide-dexamethasone is the “best possible regimen today,” Dr Palumbo said, “followed by continuous therapy.”
The 2-drug combination of lenalidomide and dexamethasone is probably more suitable for the elderly and the frail.
Alternative regimens include carfilzomib-cyclophosphamide-dexamethasone and ixazomib-lenalidomide-dexamethasone.
Continuous therapy
Continuous therapy has been “one of the major achievements” in the treatment of MM, Dr Palumbo said. Without continuous therapy, patients in complete response remain so for about 1 year when treated with conventional chemotherapy.
Investigators found that maintenance therapy significantly prolongs progression-free survival and overall survival (P=0.02). They recommend intensification with maintenance to optimize treatment efficacy and prolong survival.
Immunomodulatory drugs such as lenalidomide are the backbone of continuous therapy today.
However, ixazomib represents another option. Ixazomib maintenance has been shown to produce durable responses for a median of more than 2 years in previously untreated patients not undergoing autologous stem cell transplant.
Salvage therapy
Seven combinations are now available for salvage therapy, including those with proteasome inhibitors, monoclonal antibodies, pomalidomide, and histone deacetylase inhibitors.
Included in some of these combinations are the newer agents ixazomib, elotuzumab, and daratumumab, “which many might consider the new rituximab,” Dr Palumbo said.
Risk stratification
Dr Palumbo stressed the importance of risk stratification—both in clinical trials and in practice.
“[T]he moment you under-treat a patient, you transform a good-risk patient into a high-risk patient . . . ,” he said.
And if trials comparing treatments are not conducted within risk categories, researchers are comparing apples to oranges—good risk with high risk
The Revised International Staging System (R-ISS) for MM effectively stratifies newly diagnosed patients by combining the original ISS, chromosomal abnormalities, and serum lactate dehydrogenase levels to evaluate prognosis.
The R-ISS defines 3 new, distinct categories that researchers believe effectively define patients’ relative risk with respect to their survival.
Age and frailty
MM patients generally fall into 3 age categories: 25-64, 65-74, and 75-101.
The youngest group can receive autologous transplant, the fit patients ages 65 to 74 can receive full-dose chemotherapy, and the oldest, frailer patients should receive reduced-dose chemotherapy.
“It’s important to differentiate fit from frail,” Dr Palumbo said, “because we cannot give the same treatment schema to a 55-year-old versus 65 or 85. At 85, that schema would create a lot of toxicities.”
In frail patients, it’s always important to check which comorbidities are present using the Charlson comorbidity scale, Dr Palumbo said.
“Remember, when we put together age, chromosome abnormalities, and frailty, frailty is the most relevant prognostic factor when you add everything together,” he said.
“Two drugs versus 3 drugs doesn’t make much difference when you are starting to introduce treatment to these very frail patients with comorbidities.”
Minimal residual disease
Dr Palumbo indicated that a combination of MRI and PET-CT should be used for a more accurate indication of minimal residual disease.
“[W]e hope to have cure, [but] I don’t think, today, myeloma is a curable disease,” he said.
He clarified this by saying that patients who are in complete response and minimal residual disease-negative at 3 years do well, but, by 7 years, “something is happening.”
And at 10 years, progression-free survival has dropped off significantly, “telling us that cure is probably not yet there.”
NEW YORK—It’s important to use the best possible regimen as soon as possible when treating patients with multiple myeloma (MM), according to a speaker at Lymphoma & Myeloma 2016.
Antonio Palumbo, MD, of the University of Torino in Italy, explained that the urgency, from a biological point of view, is because myeloma accumulates genetic mutations that change the disease in a “dramatic way.”
“At diagnosis, you might have 5000 mutations, and, at first relapse, there are 12,000 mutations,” he said. “They are completely different tumors. So the first thing that we have to recognize is that, with time, myeloma is not the same. It’s becoming different tumors.”
Dr Palumbo noted that early intervention is important because genetic and epigenetic abnormalities increase as the disease progresses and becomes more resistant.
For example, if 100 patients receive first-line treatment, 40 of them will not reach the second line. Only 60 patients will receive second-line therapy, and only 35 patients will receive third-line treatment. By the fifth line, only 10 patients, or 10%, will receive it.
“If you have very good genomic stability, you can become sensitive to different treatments,” Dr Palumbo said. “But if you become a different disease, you will not be able to receive the next therapy. That’s why it’s so important . . . to use the best possible regimen as soon as possible.”
Best regimens
The triplet bortezomib-lenalidomide-dexamethasone is the “best possible regimen today,” Dr Palumbo said, “followed by continuous therapy.”
The 2-drug combination of lenalidomide and dexamethasone is probably more suitable for the elderly and the frail.
Alternative regimens include carfilzomib-cyclophosphamide-dexamethasone and ixazomib-lenalidomide-dexamethasone.
Continuous therapy
Continuous therapy has been “one of the major achievements” in the treatment of MM, Dr Palumbo said. Without continuous therapy, patients in complete response remain so for about 1 year when treated with conventional chemotherapy.
Investigators found that maintenance therapy significantly prolongs progression-free survival and overall survival (P=0.02). They recommend intensification with maintenance to optimize treatment efficacy and prolong survival.
Immunomodulatory drugs such as lenalidomide are the backbone of continuous therapy today.
However, ixazomib represents another option. Ixazomib maintenance has been shown to produce durable responses for a median of more than 2 years in previously untreated patients not undergoing autologous stem cell transplant.
Salvage therapy
Seven combinations are now available for salvage therapy, including those with proteasome inhibitors, monoclonal antibodies, pomalidomide, and histone deacetylase inhibitors.
Included in some of these combinations are the newer agents ixazomib, elotuzumab, and daratumumab, “which many might consider the new rituximab,” Dr Palumbo said.
Risk stratification
Dr Palumbo stressed the importance of risk stratification—both in clinical trials and in practice.
“[T]he moment you under-treat a patient, you transform a good-risk patient into a high-risk patient . . . ,” he said.
And if trials comparing treatments are not conducted within risk categories, researchers are comparing apples to oranges—good risk with high risk
The Revised International Staging System (R-ISS) for MM effectively stratifies newly diagnosed patients by combining the original ISS, chromosomal abnormalities, and serum lactate dehydrogenase levels to evaluate prognosis.
The R-ISS defines 3 new, distinct categories that researchers believe effectively define patients’ relative risk with respect to their survival.
Age and frailty
MM patients generally fall into 3 age categories: 25-64, 65-74, and 75-101.
The youngest group can receive autologous transplant, the fit patients ages 65 to 74 can receive full-dose chemotherapy, and the oldest, frailer patients should receive reduced-dose chemotherapy.
“It’s important to differentiate fit from frail,” Dr Palumbo said, “because we cannot give the same treatment schema to a 55-year-old versus 65 or 85. At 85, that schema would create a lot of toxicities.”
In frail patients, it’s always important to check which comorbidities are present using the Charlson comorbidity scale, Dr Palumbo said.
“Remember, when we put together age, chromosome abnormalities, and frailty, frailty is the most relevant prognostic factor when you add everything together,” he said.
“Two drugs versus 3 drugs doesn’t make much difference when you are starting to introduce treatment to these very frail patients with comorbidities.”
Minimal residual disease
Dr Palumbo indicated that a combination of MRI and PET-CT should be used for a more accurate indication of minimal residual disease.
“[W]e hope to have cure, [but] I don’t think, today, myeloma is a curable disease,” he said.
He clarified this by saying that patients who are in complete response and minimal residual disease-negative at 3 years do well, but, by 7 years, “something is happening.”
And at 10 years, progression-free survival has dropped off significantly, “telling us that cure is probably not yet there.”
Drug fails to meet endpoint in phase 3 ITP trial
The SYK inhibitor fostamatinib did not meet the primary endpoint in a phase 3 study of adults with chronic/persistent immune thrombocytopenia (ITP), according to Rigel Pharmaceuticals, Inc., the company developing the drug.
However, fostamatinib did meet that endpoint—a significantly higher incidence of stable platelet response compared to placebo—in an identical phase 3 study.
The combined data from both studies—known as FIT 1 and FIT 2—suggest fostamatinib confers a benefit over placebo.
Therefore, Rigel Pharmaceuticals is still planning to submit a new drug application for fostamatinib to the US Food and Drug Administration (FDA) next year, pending feedback from the agency.
“We believe that the totality and consistency of data from the FIT phase 3 program . . . strongly supports a clear treatment effect, with a sustained clinical benefit of fostamatinib,” said Raul Rodriguez, president and chief executive officer of Rigel Pharmaceuticals.
“We are encouraged by these results and believe that the risk/benefit ratio for fostamatinib is positive for patients with chronic/persistent ITP . . . . As a result, we will continue to pursue this opportunity. Our next step is to seek feedback from the FDA.”
About the FIT studies
Rigel’s FIT program consists of 2 identical, multicenter, randomized, double-blind studies of approximately 75 adults each—FIT 1 (Study 047) and FIT 2 (Study 048).
The patients enrolled in each study had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL of blood.
In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.
Patients were subsequently given the opportunity to enroll in an open-label, long-term, phase 3 extension study (Study 049), which is ongoing.
Patient characteristics
In FIT 1, 51 patients were randomized to fostamatinib and 25 to placebo. The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.
Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 100%), rituximab (51% and 44%), thrombopoietic agents (50% and 60%), and splenectomy (39% and 40%).
The median platelet count at baseline was 15,000/uL in the fostamatinib arm and 16,000/uL in the placebo arm.
In FIT 2, 50 patients were randomized to fostamatinib and 24 to placebo. The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.
Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 92%), rituximab (16% and 13%), thrombopoietic agents (40% and 42%), and splenectomy (28% and 38%).
The median platelet count at baseline was 16,000/uL in the fostamatinib arm and 21,000/uL in the placebo arm.
Efficacy
The primary efficacy endpoint in both studies is a stable platelet response, which is defined as achieving platelet counts greater than 50,000/uL of blood for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.
In FIT 1, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).
In FIT 2, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).
When the data from FIT 1 and FIT 2 are combined, the response rate is significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).
The response rate is significantly better in the fostamatinib arm across all subgroups, regardless of whether patients had prior splenectomy, prior exposure to thrombopoietic agents, or baseline platelet counts above or below 15,000/uL.
In the combined dataset, patients who met the primary endpoint had their platelet counts increase from a median of 18,500/uL at baseline to more than 100,000/uL at week 24 of treatment.
In addition, patients who met the primary endpoint had a timely platelet response, and that response was enduring, according to James B. Bussel, MD, a professor at Weill Cornell Medicine in New York, New York, principal investigator on the FIT phase 3 program, and a member of Rigel’s advisory/scientific board.
“The FIT phase 3 studies have both demonstrated that fostamatinib provided a robust and enduring benefit for those patients who responded to the drug,” he said.
Safety
In FIT 1, the overall incidence of adverse events (AEs) was 96% in the fostamatinib arm and 76% in the placebo arm. The incidence of serious AEs was 16% and 20%, respectively. And the incidence of treatment-related AEs was 77% and 28%, respectively.
AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (nausea, diarrhea, vomiting, abdominal pain; 61% and 20%), nausea (29% and 4%), diarrhea (45% and 16%), infection (33% and 20%), hypertension during visit (35% and 8%), and transaminase elevation (22% and 0%).
In FIT 2, the overall incidence of AEs was 71% in the fostamatinib arm and 78% in the placebo arm. The incidence of serious AEs was 10% and 26%, respectively. And the incidence of treatment-related AEs was 39% and 26%, respectively.
AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (22% in both arms), nausea (8% and 13%), diarrhea (18% and 13%), infection (22% in both arms), hypertension during visit (20% and 17%), and transaminase elevation (6% and 0%).
The SYK inhibitor fostamatinib did not meet the primary endpoint in a phase 3 study of adults with chronic/persistent immune thrombocytopenia (ITP), according to Rigel Pharmaceuticals, Inc., the company developing the drug.
However, fostamatinib did meet that endpoint—a significantly higher incidence of stable platelet response compared to placebo—in an identical phase 3 study.
The combined data from both studies—known as FIT 1 and FIT 2—suggest fostamatinib confers a benefit over placebo.
Therefore, Rigel Pharmaceuticals is still planning to submit a new drug application for fostamatinib to the US Food and Drug Administration (FDA) next year, pending feedback from the agency.
“We believe that the totality and consistency of data from the FIT phase 3 program . . . strongly supports a clear treatment effect, with a sustained clinical benefit of fostamatinib,” said Raul Rodriguez, president and chief executive officer of Rigel Pharmaceuticals.
“We are encouraged by these results and believe that the risk/benefit ratio for fostamatinib is positive for patients with chronic/persistent ITP . . . . As a result, we will continue to pursue this opportunity. Our next step is to seek feedback from the FDA.”
About the FIT studies
Rigel’s FIT program consists of 2 identical, multicenter, randomized, double-blind studies of approximately 75 adults each—FIT 1 (Study 047) and FIT 2 (Study 048).
The patients enrolled in each study had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL of blood.
In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.
Patients were subsequently given the opportunity to enroll in an open-label, long-term, phase 3 extension study (Study 049), which is ongoing.
Patient characteristics
In FIT 1, 51 patients were randomized to fostamatinib and 25 to placebo. The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.
Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 100%), rituximab (51% and 44%), thrombopoietic agents (50% and 60%), and splenectomy (39% and 40%).
The median platelet count at baseline was 15,000/uL in the fostamatinib arm and 16,000/uL in the placebo arm.
In FIT 2, 50 patients were randomized to fostamatinib and 24 to placebo. The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.
Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 92%), rituximab (16% and 13%), thrombopoietic agents (40% and 42%), and splenectomy (28% and 38%).
The median platelet count at baseline was 16,000/uL in the fostamatinib arm and 21,000/uL in the placebo arm.
Efficacy
The primary efficacy endpoint in both studies is a stable platelet response, which is defined as achieving platelet counts greater than 50,000/uL of blood for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.
In FIT 1, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).
In FIT 2, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).
When the data from FIT 1 and FIT 2 are combined, the response rate is significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).
The response rate is significantly better in the fostamatinib arm across all subgroups, regardless of whether patients had prior splenectomy, prior exposure to thrombopoietic agents, or baseline platelet counts above or below 15,000/uL.
In the combined dataset, patients who met the primary endpoint had their platelet counts increase from a median of 18,500/uL at baseline to more than 100,000/uL at week 24 of treatment.
In addition, patients who met the primary endpoint had a timely platelet response, and that response was enduring, according to James B. Bussel, MD, a professor at Weill Cornell Medicine in New York, New York, principal investigator on the FIT phase 3 program, and a member of Rigel’s advisory/scientific board.
“The FIT phase 3 studies have both demonstrated that fostamatinib provided a robust and enduring benefit for those patients who responded to the drug,” he said.
Safety
In FIT 1, the overall incidence of adverse events (AEs) was 96% in the fostamatinib arm and 76% in the placebo arm. The incidence of serious AEs was 16% and 20%, respectively. And the incidence of treatment-related AEs was 77% and 28%, respectively.
AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (nausea, diarrhea, vomiting, abdominal pain; 61% and 20%), nausea (29% and 4%), diarrhea (45% and 16%), infection (33% and 20%), hypertension during visit (35% and 8%), and transaminase elevation (22% and 0%).
In FIT 2, the overall incidence of AEs was 71% in the fostamatinib arm and 78% in the placebo arm. The incidence of serious AEs was 10% and 26%, respectively. And the incidence of treatment-related AEs was 39% and 26%, respectively.
AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (22% in both arms), nausea (8% and 13%), diarrhea (18% and 13%), infection (22% in both arms), hypertension during visit (20% and 17%), and transaminase elevation (6% and 0%).
The SYK inhibitor fostamatinib did not meet the primary endpoint in a phase 3 study of adults with chronic/persistent immune thrombocytopenia (ITP), according to Rigel Pharmaceuticals, Inc., the company developing the drug.
However, fostamatinib did meet that endpoint—a significantly higher incidence of stable platelet response compared to placebo—in an identical phase 3 study.
The combined data from both studies—known as FIT 1 and FIT 2—suggest fostamatinib confers a benefit over placebo.
Therefore, Rigel Pharmaceuticals is still planning to submit a new drug application for fostamatinib to the US Food and Drug Administration (FDA) next year, pending feedback from the agency.
“We believe that the totality and consistency of data from the FIT phase 3 program . . . strongly supports a clear treatment effect, with a sustained clinical benefit of fostamatinib,” said Raul Rodriguez, president and chief executive officer of Rigel Pharmaceuticals.
“We are encouraged by these results and believe that the risk/benefit ratio for fostamatinib is positive for patients with chronic/persistent ITP . . . . As a result, we will continue to pursue this opportunity. Our next step is to seek feedback from the FDA.”
About the FIT studies
Rigel’s FIT program consists of 2 identical, multicenter, randomized, double-blind studies of approximately 75 adults each—FIT 1 (Study 047) and FIT 2 (Study 048).
The patients enrolled in each study had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL of blood.
In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.
Patients were subsequently given the opportunity to enroll in an open-label, long-term, phase 3 extension study (Study 049), which is ongoing.
Patient characteristics
In FIT 1, 51 patients were randomized to fostamatinib and 25 to placebo. The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.
Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 100%), rituximab (51% and 44%), thrombopoietic agents (50% and 60%), and splenectomy (39% and 40%).
The median platelet count at baseline was 15,000/uL in the fostamatinib arm and 16,000/uL in the placebo arm.
In FIT 2, 50 patients were randomized to fostamatinib and 24 to placebo. The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.
Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 92%), rituximab (16% and 13%), thrombopoietic agents (40% and 42%), and splenectomy (28% and 38%).
The median platelet count at baseline was 16,000/uL in the fostamatinib arm and 21,000/uL in the placebo arm.
Efficacy
The primary efficacy endpoint in both studies is a stable platelet response, which is defined as achieving platelet counts greater than 50,000/uL of blood for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.
In FIT 1, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).
In FIT 2, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).
When the data from FIT 1 and FIT 2 are combined, the response rate is significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).
The response rate is significantly better in the fostamatinib arm across all subgroups, regardless of whether patients had prior splenectomy, prior exposure to thrombopoietic agents, or baseline platelet counts above or below 15,000/uL.
In the combined dataset, patients who met the primary endpoint had their platelet counts increase from a median of 18,500/uL at baseline to more than 100,000/uL at week 24 of treatment.
In addition, patients who met the primary endpoint had a timely platelet response, and that response was enduring, according to James B. Bussel, MD, a professor at Weill Cornell Medicine in New York, New York, principal investigator on the FIT phase 3 program, and a member of Rigel’s advisory/scientific board.
“The FIT phase 3 studies have both demonstrated that fostamatinib provided a robust and enduring benefit for those patients who responded to the drug,” he said.
Safety
In FIT 1, the overall incidence of adverse events (AEs) was 96% in the fostamatinib arm and 76% in the placebo arm. The incidence of serious AEs was 16% and 20%, respectively. And the incidence of treatment-related AEs was 77% and 28%, respectively.
AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (nausea, diarrhea, vomiting, abdominal pain; 61% and 20%), nausea (29% and 4%), diarrhea (45% and 16%), infection (33% and 20%), hypertension during visit (35% and 8%), and transaminase elevation (22% and 0%).
In FIT 2, the overall incidence of AEs was 71% in the fostamatinib arm and 78% in the placebo arm. The incidence of serious AEs was 10% and 26%, respectively. And the incidence of treatment-related AEs was 39% and 26%, respectively.
AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (22% in both arms), nausea (8% and 13%), diarrhea (18% and 13%), infection (22% in both arms), hypertension during visit (20% and 17%), and transaminase elevation (6% and 0%).
Combos produce ‘encouraging’ responses in MM
LEIPZIG, GERMANY—Combination therapies including the investigational drug MOR202 have produced “encouraging and long-lasting responses” in a phase 1/2 trial of patients with relapsed/refractory multiple myeloma (MM), according to researchers.
MOR202 is an antibody targeting CD38. In this trial, researchers are testing the drug in combination with dexamethasone (Dex), lenalidomide (Len) and Dex, or pomalidomide (Pom) and Dex.
Results thus far suggest the combinations are well-tolerated and can produce durable responses in heavily pretreated patients with relapsed/refractory MM.
The results were presented in a poster at the 2016 annual meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (abstract P235).
The study, which is ongoing, is sponsored by MorphoSys AG. The poster is available for download from the company’s website.
Treatment
This 3+3 dose-escalation study started with MOR202 monotherapy given at 0.01 mg/kg every 2 weeks, and the dose was escalated up to 16 mg/kg every 2 weeks and 8 mg/kg every week.
Once the dose-escalation phase was complete, researchers began testing MOR202 in combination with Dex, Pom and Dex, or Len and Dex.
Patients
As of September 05, 2016, 73 patients had been treated with MOR202, but the researchers only reported data on the 38 patients who received MOR202 as part of combination therapy.
Eighteen patients had received MOR202 plus Dex, 7 had received MOR202 plus Pom and Dex, and 13 had received MOR202 plus Len and Dex. The patients’ median age was 67, 64, and 64, respectively.
The median number of prior therapies was 3, 4, and 2, respectively. And the percentage of patients who were refractory to their last therapy was 78%, 100%, and 56%, respectively.
Safety
The researchers said the maximum-tolerated dose of MOR202, alone or in combination, has not yet been reached. However, the data suggest MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.
All 38 patients who received MOR202 in combination were evaluable for safety—18 in the Dex arm, 7 in the Pom/Dex arm, and 13 in the Len/Dex arm.
The most frequent grade 3 or higher adverse events were hematologic in nature. These included (in the Dex, Pom/Dex, and Len/Dex arms, respectively) leukopenia (11%, 57%, 31%), lymphopenia (39%, 29%, 54%), neutropenia (22%, 71%, 39%), thrombocytopenia (17%, 43%, 8%), and anemia (11%, 14%, 15%).
Infusion-related reactions occurred in 3 (8%) patients and were mainly limited to the first infusion. One patient developed a transient anti-MOR202 antibody response.
One patient discontinued treatment due to an adverse event that may have been caused by MOR202. However, researchers also said the event (decrease in platelet count) may have been caused by Dex.
There were no treatment-related deaths.
Efficacy
Efficacy data were available for 31 of the 38 patients. Fifteen patients responded, and 12 of these responses are ongoing for up to 56 weeks.
In all, there were 10 partial responses (PRs), 3 very good partial responses (VGPRs), and 2 complete responses (CRs).
There were 5 responses in the Dex arm—3 PRs and 2 VGPRs. There were 3 responses in the Pom/Dex arm—2 CRs and 1 PR. And there were 7 responses in the Len/Dex arm—6 PRs (3 unconfirmed) and 1 VGPR.
“We are very pleased that these results are consistent with earlier data from the ongoing trial and show further improved responses with more patients being evaluable for efficacy and safety assessment,” said Arndt Schottelius, MD, PhD, chief development officer of MorphoSys AG.
“In addition to the very short infusion time, we are particularly interested in the efficacy results in patients treated with MOR202 plus pomalidomide, who had a median of 4 prior therapies. The dose-escalation study is ongoing as planned, currently focusing on the highest dose cohorts of 16 mg/kg MOR202 in combination with pomalidomide and lenalidomide.”
LEIPZIG, GERMANY—Combination therapies including the investigational drug MOR202 have produced “encouraging and long-lasting responses” in a phase 1/2 trial of patients with relapsed/refractory multiple myeloma (MM), according to researchers.
MOR202 is an antibody targeting CD38. In this trial, researchers are testing the drug in combination with dexamethasone (Dex), lenalidomide (Len) and Dex, or pomalidomide (Pom) and Dex.
Results thus far suggest the combinations are well-tolerated and can produce durable responses in heavily pretreated patients with relapsed/refractory MM.
The results were presented in a poster at the 2016 annual meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (abstract P235).
The study, which is ongoing, is sponsored by MorphoSys AG. The poster is available for download from the company’s website.
Treatment
This 3+3 dose-escalation study started with MOR202 monotherapy given at 0.01 mg/kg every 2 weeks, and the dose was escalated up to 16 mg/kg every 2 weeks and 8 mg/kg every week.
Once the dose-escalation phase was complete, researchers began testing MOR202 in combination with Dex, Pom and Dex, or Len and Dex.
Patients
As of September 05, 2016, 73 patients had been treated with MOR202, but the researchers only reported data on the 38 patients who received MOR202 as part of combination therapy.
Eighteen patients had received MOR202 plus Dex, 7 had received MOR202 plus Pom and Dex, and 13 had received MOR202 plus Len and Dex. The patients’ median age was 67, 64, and 64, respectively.
The median number of prior therapies was 3, 4, and 2, respectively. And the percentage of patients who were refractory to their last therapy was 78%, 100%, and 56%, respectively.
Safety
The researchers said the maximum-tolerated dose of MOR202, alone or in combination, has not yet been reached. However, the data suggest MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.
All 38 patients who received MOR202 in combination were evaluable for safety—18 in the Dex arm, 7 in the Pom/Dex arm, and 13 in the Len/Dex arm.
The most frequent grade 3 or higher adverse events were hematologic in nature. These included (in the Dex, Pom/Dex, and Len/Dex arms, respectively) leukopenia (11%, 57%, 31%), lymphopenia (39%, 29%, 54%), neutropenia (22%, 71%, 39%), thrombocytopenia (17%, 43%, 8%), and anemia (11%, 14%, 15%).
Infusion-related reactions occurred in 3 (8%) patients and were mainly limited to the first infusion. One patient developed a transient anti-MOR202 antibody response.
One patient discontinued treatment due to an adverse event that may have been caused by MOR202. However, researchers also said the event (decrease in platelet count) may have been caused by Dex.
There were no treatment-related deaths.
Efficacy
Efficacy data were available for 31 of the 38 patients. Fifteen patients responded, and 12 of these responses are ongoing for up to 56 weeks.
In all, there were 10 partial responses (PRs), 3 very good partial responses (VGPRs), and 2 complete responses (CRs).
There were 5 responses in the Dex arm—3 PRs and 2 VGPRs. There were 3 responses in the Pom/Dex arm—2 CRs and 1 PR. And there were 7 responses in the Len/Dex arm—6 PRs (3 unconfirmed) and 1 VGPR.
“We are very pleased that these results are consistent with earlier data from the ongoing trial and show further improved responses with more patients being evaluable for efficacy and safety assessment,” said Arndt Schottelius, MD, PhD, chief development officer of MorphoSys AG.
“In addition to the very short infusion time, we are particularly interested in the efficacy results in patients treated with MOR202 plus pomalidomide, who had a median of 4 prior therapies. The dose-escalation study is ongoing as planned, currently focusing on the highest dose cohorts of 16 mg/kg MOR202 in combination with pomalidomide and lenalidomide.”
LEIPZIG, GERMANY—Combination therapies including the investigational drug MOR202 have produced “encouraging and long-lasting responses” in a phase 1/2 trial of patients with relapsed/refractory multiple myeloma (MM), according to researchers.
MOR202 is an antibody targeting CD38. In this trial, researchers are testing the drug in combination with dexamethasone (Dex), lenalidomide (Len) and Dex, or pomalidomide (Pom) and Dex.
Results thus far suggest the combinations are well-tolerated and can produce durable responses in heavily pretreated patients with relapsed/refractory MM.
The results were presented in a poster at the 2016 annual meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (abstract P235).
The study, which is ongoing, is sponsored by MorphoSys AG. The poster is available for download from the company’s website.
Treatment
This 3+3 dose-escalation study started with MOR202 monotherapy given at 0.01 mg/kg every 2 weeks, and the dose was escalated up to 16 mg/kg every 2 weeks and 8 mg/kg every week.
Once the dose-escalation phase was complete, researchers began testing MOR202 in combination with Dex, Pom and Dex, or Len and Dex.
Patients
As of September 05, 2016, 73 patients had been treated with MOR202, but the researchers only reported data on the 38 patients who received MOR202 as part of combination therapy.
Eighteen patients had received MOR202 plus Dex, 7 had received MOR202 plus Pom and Dex, and 13 had received MOR202 plus Len and Dex. The patients’ median age was 67, 64, and 64, respectively.
The median number of prior therapies was 3, 4, and 2, respectively. And the percentage of patients who were refractory to their last therapy was 78%, 100%, and 56%, respectively.
Safety
The researchers said the maximum-tolerated dose of MOR202, alone or in combination, has not yet been reached. However, the data suggest MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.
All 38 patients who received MOR202 in combination were evaluable for safety—18 in the Dex arm, 7 in the Pom/Dex arm, and 13 in the Len/Dex arm.
The most frequent grade 3 or higher adverse events were hematologic in nature. These included (in the Dex, Pom/Dex, and Len/Dex arms, respectively) leukopenia (11%, 57%, 31%), lymphopenia (39%, 29%, 54%), neutropenia (22%, 71%, 39%), thrombocytopenia (17%, 43%, 8%), and anemia (11%, 14%, 15%).
Infusion-related reactions occurred in 3 (8%) patients and were mainly limited to the first infusion. One patient developed a transient anti-MOR202 antibody response.
One patient discontinued treatment due to an adverse event that may have been caused by MOR202. However, researchers also said the event (decrease in platelet count) may have been caused by Dex.
There were no treatment-related deaths.
Efficacy
Efficacy data were available for 31 of the 38 patients. Fifteen patients responded, and 12 of these responses are ongoing for up to 56 weeks.
In all, there were 10 partial responses (PRs), 3 very good partial responses (VGPRs), and 2 complete responses (CRs).
There were 5 responses in the Dex arm—3 PRs and 2 VGPRs. There were 3 responses in the Pom/Dex arm—2 CRs and 1 PR. And there were 7 responses in the Len/Dex arm—6 PRs (3 unconfirmed) and 1 VGPR.
“We are very pleased that these results are consistent with earlier data from the ongoing trial and show further improved responses with more patients being evaluable for efficacy and safety assessment,” said Arndt Schottelius, MD, PhD, chief development officer of MorphoSys AG.
“In addition to the very short infusion time, we are particularly interested in the efficacy results in patients treated with MOR202 plus pomalidomide, who had a median of 4 prior therapies. The dose-escalation study is ongoing as planned, currently focusing on the highest dose cohorts of 16 mg/kg MOR202 in combination with pomalidomide and lenalidomide.”
FDA issues warning about radiation therapy devices
to receive radiation
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has warned healthcare providers to stop using radiation therapy devices manufactured and sold by Multidata Systems International Corporation.
The FDA said the company has distributed at least 2 devices in the US that were never reviewed by or registered with the FDA—(1) accessories to radiation therapy devices including the Real Time Dosimetry Waterphantom System and (2) the Dual Channel Electrometer.
Since 2003, Multidata has been under a decree that prohibits the company from designing, manufacturing, processing, and distributing medical devices, among other restrictions.
However, the FDA learned that Multidata manufactured and distributed medical devices in violation of the decree, including repairing and exchanging Waterphantom devices for newer design models.
As a result, on March 3, 2016, the FDA sent a letter to Multidata ordering the firm to stop designing, manufacturing, processing, packing, repacking, labeling, installing, holding for sale, and distributing any medical device. The company has permanently ceased operations and will be dissolving.
The FDA said it doesn’t know how many devices manufactured by Multidata are in use throughout the US or if any of these devices have caused adverse events since the decree was issued.
The agency has urged healthcare providers to stop using and dispose of any devices manufactured by Multidata.
Instead, providers should use accessories to radiation therapy devices and radiation treatment planning software that have been cleared by the FDA. Registered manufacturers of such products are listed under the IYE product code in the FDA’s Registration and Listing Database.
The FDA has also recommended that providers report any adverse events related to Multidata devices. Reports can be submitted through MedWatch, the FDA’s Safety Information and Adverse Event Reporting Program.
to receive radiation
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has warned healthcare providers to stop using radiation therapy devices manufactured and sold by Multidata Systems International Corporation.
The FDA said the company has distributed at least 2 devices in the US that were never reviewed by or registered with the FDA—(1) accessories to radiation therapy devices including the Real Time Dosimetry Waterphantom System and (2) the Dual Channel Electrometer.
Since 2003, Multidata has been under a decree that prohibits the company from designing, manufacturing, processing, and distributing medical devices, among other restrictions.
However, the FDA learned that Multidata manufactured and distributed medical devices in violation of the decree, including repairing and exchanging Waterphantom devices for newer design models.
As a result, on March 3, 2016, the FDA sent a letter to Multidata ordering the firm to stop designing, manufacturing, processing, packing, repacking, labeling, installing, holding for sale, and distributing any medical device. The company has permanently ceased operations and will be dissolving.
The FDA said it doesn’t know how many devices manufactured by Multidata are in use throughout the US or if any of these devices have caused adverse events since the decree was issued.
The agency has urged healthcare providers to stop using and dispose of any devices manufactured by Multidata.
Instead, providers should use accessories to radiation therapy devices and radiation treatment planning software that have been cleared by the FDA. Registered manufacturers of such products are listed under the IYE product code in the FDA’s Registration and Listing Database.
The FDA has also recommended that providers report any adverse events related to Multidata devices. Reports can be submitted through MedWatch, the FDA’s Safety Information and Adverse Event Reporting Program.
to receive radiation
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has warned healthcare providers to stop using radiation therapy devices manufactured and sold by Multidata Systems International Corporation.
The FDA said the company has distributed at least 2 devices in the US that were never reviewed by or registered with the FDA—(1) accessories to radiation therapy devices including the Real Time Dosimetry Waterphantom System and (2) the Dual Channel Electrometer.
Since 2003, Multidata has been under a decree that prohibits the company from designing, manufacturing, processing, and distributing medical devices, among other restrictions.
However, the FDA learned that Multidata manufactured and distributed medical devices in violation of the decree, including repairing and exchanging Waterphantom devices for newer design models.
As a result, on March 3, 2016, the FDA sent a letter to Multidata ordering the firm to stop designing, manufacturing, processing, packing, repacking, labeling, installing, holding for sale, and distributing any medical device. The company has permanently ceased operations and will be dissolving.
The FDA said it doesn’t know how many devices manufactured by Multidata are in use throughout the US or if any of these devices have caused adverse events since the decree was issued.
The agency has urged healthcare providers to stop using and dispose of any devices manufactured by Multidata.
Instead, providers should use accessories to radiation therapy devices and radiation treatment planning software that have been cleared by the FDA. Registered manufacturers of such products are listed under the IYE product code in the FDA’s Registration and Listing Database.
The FDA has also recommended that providers report any adverse events related to Multidata devices. Reports can be submitted through MedWatch, the FDA’s Safety Information and Adverse Event Reporting Program.
EBV-CTLs accepted into EMA’s PRIME program
among uninfected cells (blue)
Image courtesy of
Benjamin Chaigne-Delalande
The European Medicines Agency (EMA) has accepted into its Priority Medicines (PRIME) program an allogeneic cytotoxic T-lymphocyte product that targets Epstein-Barr virus (EBV-CTLs).
EBV-CTLs have been accepted as a treatment for patients with rituximab-refractory EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD).
The goal of the EMA’s PRIME program is to accelerate the development of therapies that target unmet medical needs.
The program provides enhanced EMA support and increased interaction to developers, in order to optimize development plans and speed regulatory evaluations to potentially bring these therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
About EBV-CTLs
The EBV-CTLs are being developed by Atara Biotherapeutics, Inc.
To create EBV-CTLs, T cells are collected from the blood of third-party donors and exposed to EBV antigens. The activated T cells are then expanded, characterized, and stored for future use in a partially HLA-matched patient.
The EBV-CTLs are designed to find cancer cells expressing EBV and kill them.
Atara Bio’s EBV-CTLs are currently being studied in phase 2 trials of patients with EBV-associated cancers, including PTLD and nasopharyngeal carcinoma.
Results from 2 studies of EBV-CTLs in rituximab-refractory PTLD were presented at the 2015 AACR Annual Meeting.
Atara Bio’s EBV-CTLs have been classified as an advanced therapy medicinal product by the EMA and have orphan designation in the European Union.
among uninfected cells (blue)
Image courtesy of
Benjamin Chaigne-Delalande
The European Medicines Agency (EMA) has accepted into its Priority Medicines (PRIME) program an allogeneic cytotoxic T-lymphocyte product that targets Epstein-Barr virus (EBV-CTLs).
EBV-CTLs have been accepted as a treatment for patients with rituximab-refractory EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD).
The goal of the EMA’s PRIME program is to accelerate the development of therapies that target unmet medical needs.
The program provides enhanced EMA support and increased interaction to developers, in order to optimize development plans and speed regulatory evaluations to potentially bring these therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
About EBV-CTLs
The EBV-CTLs are being developed by Atara Biotherapeutics, Inc.
To create EBV-CTLs, T cells are collected from the blood of third-party donors and exposed to EBV antigens. The activated T cells are then expanded, characterized, and stored for future use in a partially HLA-matched patient.
The EBV-CTLs are designed to find cancer cells expressing EBV and kill them.
Atara Bio’s EBV-CTLs are currently being studied in phase 2 trials of patients with EBV-associated cancers, including PTLD and nasopharyngeal carcinoma.
Results from 2 studies of EBV-CTLs in rituximab-refractory PTLD were presented at the 2015 AACR Annual Meeting.
Atara Bio’s EBV-CTLs have been classified as an advanced therapy medicinal product by the EMA and have orphan designation in the European Union.
among uninfected cells (blue)
Image courtesy of
Benjamin Chaigne-Delalande
The European Medicines Agency (EMA) has accepted into its Priority Medicines (PRIME) program an allogeneic cytotoxic T-lymphocyte product that targets Epstein-Barr virus (EBV-CTLs).
EBV-CTLs have been accepted as a treatment for patients with rituximab-refractory EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD).
The goal of the EMA’s PRIME program is to accelerate the development of therapies that target unmet medical needs.
The program provides enhanced EMA support and increased interaction to developers, in order to optimize development plans and speed regulatory evaluations to potentially bring these therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
About EBV-CTLs
The EBV-CTLs are being developed by Atara Biotherapeutics, Inc.
To create EBV-CTLs, T cells are collected from the blood of third-party donors and exposed to EBV antigens. The activated T cells are then expanded, characterized, and stored for future use in a partially HLA-matched patient.
The EBV-CTLs are designed to find cancer cells expressing EBV and kill them.
Atara Bio’s EBV-CTLs are currently being studied in phase 2 trials of patients with EBV-associated cancers, including PTLD and nasopharyngeal carcinoma.
Results from 2 studies of EBV-CTLs in rituximab-refractory PTLD were presented at the 2015 AACR Annual Meeting.
Atara Bio’s EBV-CTLs have been classified as an advanced therapy medicinal product by the EMA and have orphan designation in the European Union.
Burden of cancer varies by cancer type, race
Photo by Rhoda Baer
A new study suggests that leukemia and non-Hodgkin lymphoma (NHL) are among the top 10 cancers with the greatest burden (most years of healthy life lost) in the US.
The research also showed that the burden of different cancer types varied between patients belonging to different racial/ethnic groups.
For example, the contribution of leukemia to the overall cancer burden was twice as high in Hispanics as it was in non-Hispanic blacks. The same was true for NHL.
Joannie Lortet-Tieulent, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in the American Journal of Preventive Medicine.
The researchers calculated the burden of cancer in the US in 2011 for 24 cancer types. They calculated burden using disability-adjusted life years (DALYs), which combine cancer incidence, mortality, survival, and quality of life into a summary indicator.
The results suggested the burden of cancer in 2011 was over 9.8 million DALYs, which was equally shared between men and women—4.9 million DALYs for each sex.
DALYs lost to cancer were mostly related to premature death due to cancer (91%). The remaining 9% were related to impaired quality of life because of the disease or its treatment, or other disease-related issues.
Top 10 contributors
The researchers calculated the proportion of DALYs lost for each of the cancer types. And they found that lung cancer was the largest contributor to the loss of healthy years, accounting for 24% of the burden (2.4 million DALYs).
The second biggest contributor to the loss of healthy years was breast cancer (10%), followed by colorectal cancer (9%), pancreatic cancer (6%), prostate cancer (5%), leukemia (4%), liver cancer (4%), brain cancer (3%), NHL (3%), and ovarian cancer (3%).
The researchers also calculated the proportion of DALYs lost from the top 10 cancer types according to race/ethnicity.
They found the contribution of leukemia to the loss of healthy years was greatest for Hispanics (6%), followed by non-Hispanic Asians (5%), non-Hispanic whites (4%), and non-Hispanic blacks (3%).
The contribution of NHL to the loss of healthy years was greatest for Hispanics (4%), followed by non-Hispanic Asians/non-Hispanic whites (3% for both), and non-Hispanic blacks (2%).
DALYs by race/ethnicity
The researchers found that, overall, the cancer burden was highest in non-Hispanic blacks, followed by non-Hispanic whites, Hispanics, and non-Hispanic Asians. However, this pattern was not consistent across the different cancer types.
Age-standardized DALYs lost (per 100,000 individuals) were as follows:
All cancers combined
3588 for non-Hispanic blacks
2898 for non-Hispanic whites
1978 for Hispanics
1798 for non-Hispanic Asians.
Leukemia
115 for non-Hispanic blacks and non-Hispanic whites
98 for Hispanics
82 for non-Hispanic Asians.
NHL
93 for non-Hispanic whites
86 for non-Hispanic blacks
78 for Hispanics
60 for non-Hispanic Asians.
Hodgkin lymphoma
11 for non-Hispanic blacks
10 for non-Hispanic whites and Hispanics
3 for non-Hispanic Asians.
Myeloma
93 for non-Hispanic blacks
43 for non-Hispanic whites
42 for Hispanics
26 for non-Hispanic Asians.
The researchers noted that, despite these differences, the cancer burden in all races/ethnicities was driven by years of life lost. They said this highlights the need to prevent deaths by improving prevention, early detection, and treatment of cancers.
Photo by Rhoda Baer
A new study suggests that leukemia and non-Hodgkin lymphoma (NHL) are among the top 10 cancers with the greatest burden (most years of healthy life lost) in the US.
The research also showed that the burden of different cancer types varied between patients belonging to different racial/ethnic groups.
For example, the contribution of leukemia to the overall cancer burden was twice as high in Hispanics as it was in non-Hispanic blacks. The same was true for NHL.
Joannie Lortet-Tieulent, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in the American Journal of Preventive Medicine.
The researchers calculated the burden of cancer in the US in 2011 for 24 cancer types. They calculated burden using disability-adjusted life years (DALYs), which combine cancer incidence, mortality, survival, and quality of life into a summary indicator.
The results suggested the burden of cancer in 2011 was over 9.8 million DALYs, which was equally shared between men and women—4.9 million DALYs for each sex.
DALYs lost to cancer were mostly related to premature death due to cancer (91%). The remaining 9% were related to impaired quality of life because of the disease or its treatment, or other disease-related issues.
Top 10 contributors
The researchers calculated the proportion of DALYs lost for each of the cancer types. And they found that lung cancer was the largest contributor to the loss of healthy years, accounting for 24% of the burden (2.4 million DALYs).
The second biggest contributor to the loss of healthy years was breast cancer (10%), followed by colorectal cancer (9%), pancreatic cancer (6%), prostate cancer (5%), leukemia (4%), liver cancer (4%), brain cancer (3%), NHL (3%), and ovarian cancer (3%).
The researchers also calculated the proportion of DALYs lost from the top 10 cancer types according to race/ethnicity.
They found the contribution of leukemia to the loss of healthy years was greatest for Hispanics (6%), followed by non-Hispanic Asians (5%), non-Hispanic whites (4%), and non-Hispanic blacks (3%).
The contribution of NHL to the loss of healthy years was greatest for Hispanics (4%), followed by non-Hispanic Asians/non-Hispanic whites (3% for both), and non-Hispanic blacks (2%).
DALYs by race/ethnicity
The researchers found that, overall, the cancer burden was highest in non-Hispanic blacks, followed by non-Hispanic whites, Hispanics, and non-Hispanic Asians. However, this pattern was not consistent across the different cancer types.
Age-standardized DALYs lost (per 100,000 individuals) were as follows:
All cancers combined
3588 for non-Hispanic blacks
2898 for non-Hispanic whites
1978 for Hispanics
1798 for non-Hispanic Asians.
Leukemia
115 for non-Hispanic blacks and non-Hispanic whites
98 for Hispanics
82 for non-Hispanic Asians.
NHL
93 for non-Hispanic whites
86 for non-Hispanic blacks
78 for Hispanics
60 for non-Hispanic Asians.
Hodgkin lymphoma
11 for non-Hispanic blacks
10 for non-Hispanic whites and Hispanics
3 for non-Hispanic Asians.
Myeloma
93 for non-Hispanic blacks
43 for non-Hispanic whites
42 for Hispanics
26 for non-Hispanic Asians.
The researchers noted that, despite these differences, the cancer burden in all races/ethnicities was driven by years of life lost. They said this highlights the need to prevent deaths by improving prevention, early detection, and treatment of cancers.
Photo by Rhoda Baer
A new study suggests that leukemia and non-Hodgkin lymphoma (NHL) are among the top 10 cancers with the greatest burden (most years of healthy life lost) in the US.
The research also showed that the burden of different cancer types varied between patients belonging to different racial/ethnic groups.
For example, the contribution of leukemia to the overall cancer burden was twice as high in Hispanics as it was in non-Hispanic blacks. The same was true for NHL.
Joannie Lortet-Tieulent, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in the American Journal of Preventive Medicine.
The researchers calculated the burden of cancer in the US in 2011 for 24 cancer types. They calculated burden using disability-adjusted life years (DALYs), which combine cancer incidence, mortality, survival, and quality of life into a summary indicator.
The results suggested the burden of cancer in 2011 was over 9.8 million DALYs, which was equally shared between men and women—4.9 million DALYs for each sex.
DALYs lost to cancer were mostly related to premature death due to cancer (91%). The remaining 9% were related to impaired quality of life because of the disease or its treatment, or other disease-related issues.
Top 10 contributors
The researchers calculated the proportion of DALYs lost for each of the cancer types. And they found that lung cancer was the largest contributor to the loss of healthy years, accounting for 24% of the burden (2.4 million DALYs).
The second biggest contributor to the loss of healthy years was breast cancer (10%), followed by colorectal cancer (9%), pancreatic cancer (6%), prostate cancer (5%), leukemia (4%), liver cancer (4%), brain cancer (3%), NHL (3%), and ovarian cancer (3%).
The researchers also calculated the proportion of DALYs lost from the top 10 cancer types according to race/ethnicity.
They found the contribution of leukemia to the loss of healthy years was greatest for Hispanics (6%), followed by non-Hispanic Asians (5%), non-Hispanic whites (4%), and non-Hispanic blacks (3%).
The contribution of NHL to the loss of healthy years was greatest for Hispanics (4%), followed by non-Hispanic Asians/non-Hispanic whites (3% for both), and non-Hispanic blacks (2%).
DALYs by race/ethnicity
The researchers found that, overall, the cancer burden was highest in non-Hispanic blacks, followed by non-Hispanic whites, Hispanics, and non-Hispanic Asians. However, this pattern was not consistent across the different cancer types.
Age-standardized DALYs lost (per 100,000 individuals) were as follows:
All cancers combined
3588 for non-Hispanic blacks
2898 for non-Hispanic whites
1978 for Hispanics
1798 for non-Hispanic Asians.
Leukemia
115 for non-Hispanic blacks and non-Hispanic whites
98 for Hispanics
82 for non-Hispanic Asians.
NHL
93 for non-Hispanic whites
86 for non-Hispanic blacks
78 for Hispanics
60 for non-Hispanic Asians.
Hodgkin lymphoma
11 for non-Hispanic blacks
10 for non-Hispanic whites and Hispanics
3 for non-Hispanic Asians.
Myeloma
93 for non-Hispanic blacks
43 for non-Hispanic whites
42 for Hispanics
26 for non-Hispanic Asians.
The researchers noted that, despite these differences, the cancer burden in all races/ethnicities was driven by years of life lost. They said this highlights the need to prevent deaths by improving prevention, early detection, and treatment of cancers.