Pharmacy

By Crystal (Crystl) from Bloomington, USA - Flickr

The US Food and Drug Administration (FDA) has granted priority review for emicizumab (Hemlibra®) for adults and children with hemophilia A without factor VIII inhibitors.

Earlier this year, the agency awarded emicizumab breakthrough therapy designation for the same population.

Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.

The FDA based its decision to grant emicizumab priority review on the phase 3 HAVEN 3 study, results of which were presented recently at the World Federation of Hemophilia congress.

In HAVEN 3, emicizumab demonstrated a 68% reduction (P<0.0001) in treated bleeds based on an intra-patient comparison in patients who were previously enrolled in a prospective non-interventional study.

According to Genentech, co-developer of the drug, this makes emicizumab the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the current standard of care for people with hemophilia A without factor VIII inhibitors.

About HAVEN 3

The randomized, multicenter, open-label trial evaluated prophylaxis versus no prophylaxis in patients without factor VIII inhibitors.

The study included 152 patients 12 years or older who were previously treated with factor VIII therapy on-demand or as prophylaxis.

Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to 1 of 3 treatment groups:

• Arm A received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
• Arm B received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks.
• Arm C received no prophylaxis

Patients previously treated prophylactically with factor VIII were enrolled in Arm D and received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.

The protocol permitted episodic treatment of breakthrough bleeds with factor VIII therapy.

Patients in the prophylaxis groups achieved a 96% (P<0.0001) and 97% (P<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis.

Additionally, 55.6% of patients treated weekly and 60% treated every 2 weeks had no treated bleeds. In contrast, 0% in the prophylaxis group achieved zero treated bleeds.

Investigators observed no unexpected or serious adverse events (AEs), no thrombotic events, and no cases of thrombotic microangiopathy.

The most common AEs occurring in 5% or more of patients were injection site reactions, arthralgia, nasopharyngitis, headache, upper respiratory tract infection, and influenza.

The FDA is expected to make a decision regarding approval by October 4. 

By Crystal (Crystl) from Bloomington, USA - Flickr

The US Food and Drug Administration (FDA) has granted priority review for emicizumab (Hemlibra®) for adults and children with hemophilia A without factor VIII inhibitors.

Earlier this year, the agency awarded emicizumab breakthrough therapy designation for the same population.

Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.

The FDA based its decision to grant emicizumab priority review on the phase 3 HAVEN 3 study, results of which were presented recently at the World Federation of Hemophilia congress.

In HAVEN 3, emicizumab demonstrated a 68% reduction (P<0.0001) in treated bleeds based on an intra-patient comparison in patients who were previously enrolled in a prospective non-interventional study.

According to Genentech, co-developer of the drug, this makes emicizumab the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the current standard of care for people with hemophilia A without factor VIII inhibitors.

About HAVEN 3

The randomized, multicenter, open-label trial evaluated prophylaxis versus no prophylaxis in patients without factor VIII inhibitors.

The study included 152 patients 12 years or older who were previously treated with factor VIII therapy on-demand or as prophylaxis.

Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to 1 of 3 treatment groups:

• Arm A received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
• Arm B received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks.
• Arm C received no prophylaxis

Patients previously treated prophylactically with factor VIII were enrolled in Arm D and received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.

The protocol permitted episodic treatment of breakthrough bleeds with factor VIII therapy.

Patients in the prophylaxis groups achieved a 96% (P<0.0001) and 97% (P<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis.

Additionally, 55.6% of patients treated weekly and 60% treated every 2 weeks had no treated bleeds. In contrast, 0% in the prophylaxis group achieved zero treated bleeds.

Investigators observed no unexpected or serious adverse events (AEs), no thrombotic events, and no cases of thrombotic microangiopathy.

The most common AEs occurring in 5% or more of patients were injection site reactions, arthralgia, nasopharyngitis, headache, upper respiratory tract infection, and influenza.

The FDA is expected to make a decision regarding approval by October 4. 

By Crystal (Crystl) from Bloomington, USA - Flickr

The US Food and Drug Administration (FDA) has granted priority review for emicizumab (Hemlibra®) for adults and children with hemophilia A without factor VIII inhibitors.

Earlier this year, the agency awarded emicizumab breakthrough therapy designation for the same population.

Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.

The FDA based its decision to grant emicizumab priority review on the phase 3 HAVEN 3 study, results of which were presented recently at the World Federation of Hemophilia congress.

In HAVEN 3, emicizumab demonstrated a 68% reduction (P<0.0001) in treated bleeds based on an intra-patient comparison in patients who were previously enrolled in a prospective non-interventional study.

According to Genentech, co-developer of the drug, this makes emicizumab the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the current standard of care for people with hemophilia A without factor VIII inhibitors.

About HAVEN 3

The randomized, multicenter, open-label trial evaluated prophylaxis versus no prophylaxis in patients without factor VIII inhibitors.

The study included 152 patients 12 years or older who were previously treated with factor VIII therapy on-demand or as prophylaxis.

Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to 1 of 3 treatment groups:

• Arm A received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
• Arm B received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks.
• Arm C received no prophylaxis

Patients previously treated prophylactically with factor VIII were enrolled in Arm D and received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.

The protocol permitted episodic treatment of breakthrough bleeds with factor VIII therapy.

Patients in the prophylaxis groups achieved a 96% (P<0.0001) and 97% (P<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis.

Additionally, 55.6% of patients treated weekly and 60% treated every 2 weeks had no treated bleeds. In contrast, 0% in the prophylaxis group achieved zero treated bleeds.

Investigators observed no unexpected or serious adverse events (AEs), no thrombotic events, and no cases of thrombotic microangiopathy.

The most common AEs occurring in 5% or more of patients were injection site reactions, arthralgia, nasopharyngitis, headache, upper respiratory tract infection, and influenza.

The FDA is expected to make a decision regarding approval by October 4. 

Vials and a syringe

The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.

The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.

The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.

A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.

A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.

Common side effects of Fulphila include bone pain and pain in extremities.

The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.

Serious side effects from Fulphila include:

• rupture of the spleen
• acute respiratory distress syndrome
• serious allergic reactions including anaphylaxis
• glomerulonephritis
• leukocytosis
• capillary leak syndrome
• potential for tumor growth

Fatal sickle cell crises have also occurred with Fulphila use.

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.

“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.

The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.

Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.

The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.

Mylan anticipates launching Fulphila in the coming weeks. 

Vials and a syringe

The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.

The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.

The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.

A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.

A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.

Common side effects of Fulphila include bone pain and pain in extremities.

The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.

Serious side effects from Fulphila include:

• rupture of the spleen
• acute respiratory distress syndrome
• serious allergic reactions including anaphylaxis
• glomerulonephritis
• leukocytosis
• capillary leak syndrome
• potential for tumor growth

Fatal sickle cell crises have also occurred with Fulphila use.

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.

“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.

The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.

Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.

The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.

Mylan anticipates launching Fulphila in the coming weeks. 

Vials and a syringe

The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.

The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.

The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.

A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.

A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.

Common side effects of Fulphila include bone pain and pain in extremities.

The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.

Serious side effects from Fulphila include:

• rupture of the spleen
• acute respiratory distress syndrome
• serious allergic reactions including anaphylaxis
• glomerulonephritis
• leukocytosis
• capillary leak syndrome
• potential for tumor growth

Fatal sickle cell crises have also occurred with Fulphila use.

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.

“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.

The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.

Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.

The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.

Mylan anticipates launching Fulphila in the coming weeks. 

Photo by Bill Branson

Currently, 1,120 new medicines and vaccines are being developed to treat cancer, according to a new report of the Pharmaceutical Research and Manufacturers of America (PhRMA).

And all of them, the organization states, are in clinical trials or awaiting review by the US Food and Drug Administration (FDA).

Leading the way are treatments for solid tumors, with 397 in development. Treatments for blood cancers are not far behind, with nearly 340 medicines in development: 137 for leukemias, 135 for lymphomas, and 62 for multiple myeloma.

Immuno-oncology and personalized medicine have a hand in this increase.

In the last year, according to PhRMA’s  "Medicines in Development for Cancer 2018 Report," 47 new immune-oncology treatments have been added to the development pipeline, including CAR-T therapies and checkpoint inhibitors.

This brings the total to 295 immuno-oncology medicines and vaccines in the development pipeline this year.

The report also states that about 85% of these medicines in the oncology pipeline are first-in-class.

And PhRMA attributes the approximately 73% of survival gains in cancer to the new medicines.

Despite the bright picture, PhRMA acknowledges the financial burden and medical care challenges patients encounter.

It addresses them in a new chart pack, "Cancer Medicines: Value in Context," which puts cancer costs in perspective and offers solutions for improving the current system in the United States.

The association reports the top medical financial concerns of patients to be diagnostic tests or scans (53%), prescription medicines (43%), physician office visits (39%), outpatient treatments-including radiation (37%), and surgery (36%).

Spending on cancer medicines represents about 1% of overall healthcare spending, according to the organization, with cancer medications accounting for $49.8 billion of the $3.49 trillion healthcare spending in the United States.

Cancer medicines represent about 20% of spending on cancer, PhrMA notes, and some insurance plans place treatments for certain high-cost conditions on the highest drug formulary cost-sharing tier.

And patients with the highest copay were 5 times more likely to abandon treatment than the lowest copay group, PhRMA points out.

“No patient should struggle to afford their needed treatments,” PhRMA stated in a release, “and it is important that we address patient access challenges.” 

Photo by Bill Branson

Currently, 1,120 new medicines and vaccines are being developed to treat cancer, according to a new report of the Pharmaceutical Research and Manufacturers of America (PhRMA).

And all of them, the organization states, are in clinical trials or awaiting review by the US Food and Drug Administration (FDA).

Leading the way are treatments for solid tumors, with 397 in development. Treatments for blood cancers are not far behind, with nearly 340 medicines in development: 137 for leukemias, 135 for lymphomas, and 62 for multiple myeloma.

Immuno-oncology and personalized medicine have a hand in this increase.

In the last year, according to PhRMA’s  "Medicines in Development for Cancer 2018 Report," 47 new immune-oncology treatments have been added to the development pipeline, including CAR-T therapies and checkpoint inhibitors.

This brings the total to 295 immuno-oncology medicines and vaccines in the development pipeline this year.

The report also states that about 85% of these medicines in the oncology pipeline are first-in-class.

And PhRMA attributes the approximately 73% of survival gains in cancer to the new medicines.

Despite the bright picture, PhRMA acknowledges the financial burden and medical care challenges patients encounter.

It addresses them in a new chart pack, "Cancer Medicines: Value in Context," which puts cancer costs in perspective and offers solutions for improving the current system in the United States.

The association reports the top medical financial concerns of patients to be diagnostic tests or scans (53%), prescription medicines (43%), physician office visits (39%), outpatient treatments-including radiation (37%), and surgery (36%).

Spending on cancer medicines represents about 1% of overall healthcare spending, according to the organization, with cancer medications accounting for $49.8 billion of the $3.49 trillion healthcare spending in the United States.

Cancer medicines represent about 20% of spending on cancer, PhrMA notes, and some insurance plans place treatments for certain high-cost conditions on the highest drug formulary cost-sharing tier.

And patients with the highest copay were 5 times more likely to abandon treatment than the lowest copay group, PhRMA points out.

“No patient should struggle to afford their needed treatments,” PhRMA stated in a release, “and it is important that we address patient access challenges.” 

Photo by Bill Branson

Currently, 1,120 new medicines and vaccines are being developed to treat cancer, according to a new report of the Pharmaceutical Research and Manufacturers of America (PhRMA).

And all of them, the organization states, are in clinical trials or awaiting review by the US Food and Drug Administration (FDA).

Leading the way are treatments for solid tumors, with 397 in development. Treatments for blood cancers are not far behind, with nearly 340 medicines in development: 137 for leukemias, 135 for lymphomas, and 62 for multiple myeloma.

Immuno-oncology and personalized medicine have a hand in this increase.

In the last year, according to PhRMA’s  "Medicines in Development for Cancer 2018 Report," 47 new immune-oncology treatments have been added to the development pipeline, including CAR-T therapies and checkpoint inhibitors.

This brings the total to 295 immuno-oncology medicines and vaccines in the development pipeline this year.

The report also states that about 85% of these medicines in the oncology pipeline are first-in-class.

And PhRMA attributes the approximately 73% of survival gains in cancer to the new medicines.

Despite the bright picture, PhRMA acknowledges the financial burden and medical care challenges patients encounter.

It addresses them in a new chart pack, "Cancer Medicines: Value in Context," which puts cancer costs in perspective and offers solutions for improving the current system in the United States.

The association reports the top medical financial concerns of patients to be diagnostic tests or scans (53%), prescription medicines (43%), physician office visits (39%), outpatient treatments-including radiation (37%), and surgery (36%).

Spending on cancer medicines represents about 1% of overall healthcare spending, according to the organization, with cancer medications accounting for $49.8 billion of the $3.49 trillion healthcare spending in the United States.

Cancer medicines represent about 20% of spending on cancer, PhrMA notes, and some insurance plans place treatments for certain high-cost conditions on the highest drug formulary cost-sharing tier.

And patients with the highest copay were 5 times more likely to abandon treatment than the lowest copay group, PhRMA points out.

“No patient should struggle to afford their needed treatments,” PhRMA stated in a release, “and it is important that we address patient access challenges.” 

Photo courtesy of GSK

Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).

The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.

And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.

Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.

The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Trial data

Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.

Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.

The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).

The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.

At a median follow-up of 2 years, the overall survival rate was 97%.

In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.

Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.

Eltrombopag is marketed as Revolade in countries outside the US. 

Photo courtesy of GSK

Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).

The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.

And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.

Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.

The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Trial data

Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.

Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.

The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).

The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.

At a median follow-up of 2 years, the overall survival rate was 97%.

In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.

Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.

Eltrombopag is marketed as Revolade in countries outside the US. 

Photo courtesy of GSK

Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).

The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.

And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.

Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.

The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Trial data

Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.

Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.

The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).

The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.

At a median follow-up of 2 years, the overall survival rate was 97%.

In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.

Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.

Eltrombopag is marketed as Revolade in countries outside the US. 

AML cells

The US Food and Drug Administration (FDA) has granted priority review to gilteritinib for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have a FLT3 mutation.

At present, no FLT3-targeting agents are approved for the treatment of R/R FLT3-mutation-positive AML, according to Astellas, the developer of the drug.

The FDA previously granted gilteritinib orphan drug designation and fast track designation.

The European Commission (EC) also granted gilteritinib orphan designation and the Japan Ministry of Health, Labor and Welfare (MHLW) did likewise.

Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT tyrosine kinase domain (TKD) mutation. These 2 FLT3 mutations are present in approximately 1/3 of AML patients.

The priority review for the new drug application is based on the ongoing phase 3 ADMIRAL trial.

The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The goal date for a decision by the FDA is the end of November.

ADMIRAL trial (NCT02421939)

This open-label multicenter randomized study compares gilteritinib with salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy.

The study has enrolled 371 patients with FLT3 mutations present in bone marrow or whole blood, as determined by a central lab.

Patients were randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy.

Salvage chemotherapy could consist of low-dose cytarabine, azacitidine, MEC (mitoxantrone, etoposide, cytarabine) induction chemotherapy, or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor [G-CSF] with idarubicin) induction chemotherapy.

The primary endpoints of the study are overall survival and complete remission or complete remission with partial hematologic recovery.

Secondary endpoints include event-free survival, complete remission rate, leukemia-free survival, duration of remission, transplantation rate, fatigue inventory, among other outcomes.

The study is estimated to be completed in October for its primary endpoint and February 2020 for the entire study.  

AML cells

The US Food and Drug Administration (FDA) has granted priority review to gilteritinib for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have a FLT3 mutation.

At present, no FLT3-targeting agents are approved for the treatment of R/R FLT3-mutation-positive AML, according to Astellas, the developer of the drug.

The FDA previously granted gilteritinib orphan drug designation and fast track designation.

The European Commission (EC) also granted gilteritinib orphan designation and the Japan Ministry of Health, Labor and Welfare (MHLW) did likewise.

Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT tyrosine kinase domain (TKD) mutation. These 2 FLT3 mutations are present in approximately 1/3 of AML patients.

The priority review for the new drug application is based on the ongoing phase 3 ADMIRAL trial.

The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The goal date for a decision by the FDA is the end of November.

ADMIRAL trial (NCT02421939)

This open-label multicenter randomized study compares gilteritinib with salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy.

The study has enrolled 371 patients with FLT3 mutations present in bone marrow or whole blood, as determined by a central lab.

Patients were randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy.

Salvage chemotherapy could consist of low-dose cytarabine, azacitidine, MEC (mitoxantrone, etoposide, cytarabine) induction chemotherapy, or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor [G-CSF] with idarubicin) induction chemotherapy.

The primary endpoints of the study are overall survival and complete remission or complete remission with partial hematologic recovery.

Secondary endpoints include event-free survival, complete remission rate, leukemia-free survival, duration of remission, transplantation rate, fatigue inventory, among other outcomes.

The study is estimated to be completed in October for its primary endpoint and February 2020 for the entire study.  

AML cells

The US Food and Drug Administration (FDA) has granted priority review to gilteritinib for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have a FLT3 mutation.

At present, no FLT3-targeting agents are approved for the treatment of R/R FLT3-mutation-positive AML, according to Astellas, the developer of the drug.

The FDA previously granted gilteritinib orphan drug designation and fast track designation.

The European Commission (EC) also granted gilteritinib orphan designation and the Japan Ministry of Health, Labor and Welfare (MHLW) did likewise.

Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT tyrosine kinase domain (TKD) mutation. These 2 FLT3 mutations are present in approximately 1/3 of AML patients.

The priority review for the new drug application is based on the ongoing phase 3 ADMIRAL trial.

The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The goal date for a decision by the FDA is the end of November.

ADMIRAL trial (NCT02421939)

This open-label multicenter randomized study compares gilteritinib with salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy.

The study has enrolled 371 patients with FLT3 mutations present in bone marrow or whole blood, as determined by a central lab.

Patients were randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy.

Salvage chemotherapy could consist of low-dose cytarabine, azacitidine, MEC (mitoxantrone, etoposide, cytarabine) induction chemotherapy, or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor [G-CSF] with idarubicin) induction chemotherapy.

The primary endpoints of the study are overall survival and complete remission or complete remission with partial hematologic recovery.

Secondary endpoints include event-free survival, complete remission rate, leukemia-free survival, duration of remission, transplantation rate, fatigue inventory, among other outcomes.

The study is estimated to be completed in October for its primary endpoint and February 2020 for the entire study.  

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has released a list of companies that “may be pursuing gaming tactics to delay generic competition.”

FDA Commissioner Scott Gottlieb, MD, said the agency is taking steps to improve access to drugs and make them more affordable.

One of these steps is trying to prevent companies that market brand-name drugs from delaying the release of generic equivalents.

Dr Gottlieb explained that brand companies may create obstacles for generic developers to purchase samples of a brand-name drug.

“In general, generic drug developers need the samples of the brand drug to develop their generic product and/or to conduct testing to show that their product is bioequivalent to the brand drug for FDA approval,” he said.

“Without these samples, generic drug makers may not be able to develop generic alternatives. Yet the FDA has heard that some brand companies will adopt tactics to make it hard for the generic companies to purchase these brand drugs at a fair value and in the open marketplace.”

One such tactic is for brand companies to place restrictions in their commercial contracts or agreements with prescription drug distributors, wholesalers, or specialty pharmacies that limit their ability to sell samples to generic drug developers.

In other cases, brand companies may be preventing generic drug developers from accessing samples due to limited distribution programs required by a Risk Evaluation and Mitigation Strategy (REMS) with Elements to Assure Safe Use (ETASU).

“But I want to be very clear: a path to securing samples of brand drugs for the purpose of generic drug development should always be available,” Dr Gottlieb said. “Even in the case of limited distribution programs, such as those required by certain REMS, there should be a path forward for generic drug development.”

With this in mind, the FDA has released a list of brand companies that may have prevented generic drug developers from accessing samples. The list contains 52 brand-name drugs, including Pomalyst, Promacta, Revlimid, Tasigna, and Thalidomid.

Generic drug developers have reported trouble obtaining samples of these drugs and asked the FDA for assistance.

When the FDA receives such a request, the agency first determines whether the product in question has a REMS program with ETASU that may impact distribution.

If the FDA confirms the existence of such a program, the generic company can submit its bioequivalence testing protocol to the FDA. The agency then evaluates this protocol to ensure the plan for testing the product contains safety protections comparable to the brand product’s REMS program.

If a generic developer’s plans include appropriate protections, the developer can request that the FDA send a Safety Determination Letter to the brand company. This letter notes that the REMS program doesn’t prevent the brand company from selling its product to generic drug developers.

The FDA has issued 21 Safety Determination Letters to date, according to Dr Gottlieb.

If a generic drug developer has trouble obtaining samples of a drug for which there is no REMS program with ETASU, the FDA informs the developer that there are no FDA-required restrictions that would prevent it from obtaining samples.

The FDA also notifies the Federal Trade Commission (FTC) of requests from generic drug developers seeking assistance in obtaining samples from brand companies. And the FDA encourages generic drug developers to raise these cases with the FTC if they believe that anticompetitive conduct has taken place.

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has released a list of companies that “may be pursuing gaming tactics to delay generic competition.”

FDA Commissioner Scott Gottlieb, MD, said the agency is taking steps to improve access to drugs and make them more affordable.

One of these steps is trying to prevent companies that market brand-name drugs from delaying the release of generic equivalents.

Dr Gottlieb explained that brand companies may create obstacles for generic developers to purchase samples of a brand-name drug.

“In general, generic drug developers need the samples of the brand drug to develop their generic product and/or to conduct testing to show that their product is bioequivalent to the brand drug for FDA approval,” he said.

“Without these samples, generic drug makers may not be able to develop generic alternatives. Yet the FDA has heard that some brand companies will adopt tactics to make it hard for the generic companies to purchase these brand drugs at a fair value and in the open marketplace.”

One such tactic is for brand companies to place restrictions in their commercial contracts or agreements with prescription drug distributors, wholesalers, or specialty pharmacies that limit their ability to sell samples to generic drug developers.

In other cases, brand companies may be preventing generic drug developers from accessing samples due to limited distribution programs required by a Risk Evaluation and Mitigation Strategy (REMS) with Elements to Assure Safe Use (ETASU).

“But I want to be very clear: a path to securing samples of brand drugs for the purpose of generic drug development should always be available,” Dr Gottlieb said. “Even in the case of limited distribution programs, such as those required by certain REMS, there should be a path forward for generic drug development.”

With this in mind, the FDA has released a list of brand companies that may have prevented generic drug developers from accessing samples. The list contains 52 brand-name drugs, including Pomalyst, Promacta, Revlimid, Tasigna, and Thalidomid.

Generic drug developers have reported trouble obtaining samples of these drugs and asked the FDA for assistance.

When the FDA receives such a request, the agency first determines whether the product in question has a REMS program with ETASU that may impact distribution.

If the FDA confirms the existence of such a program, the generic company can submit its bioequivalence testing protocol to the FDA. The agency then evaluates this protocol to ensure the plan for testing the product contains safety protections comparable to the brand product’s REMS program.

If a generic developer’s plans include appropriate protections, the developer can request that the FDA send a Safety Determination Letter to the brand company. This letter notes that the REMS program doesn’t prevent the brand company from selling its product to generic drug developers.

The FDA has issued 21 Safety Determination Letters to date, according to Dr Gottlieb.

If a generic drug developer has trouble obtaining samples of a drug for which there is no REMS program with ETASU, the FDA informs the developer that there are no FDA-required restrictions that would prevent it from obtaining samples.

The FDA also notifies the Federal Trade Commission (FTC) of requests from generic drug developers seeking assistance in obtaining samples from brand companies. And the FDA encourages generic drug developers to raise these cases with the FTC if they believe that anticompetitive conduct has taken place.

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has released a list of companies that “may be pursuing gaming tactics to delay generic competition.”

FDA Commissioner Scott Gottlieb, MD, said the agency is taking steps to improve access to drugs and make them more affordable.

One of these steps is trying to prevent companies that market brand-name drugs from delaying the release of generic equivalents.

Dr Gottlieb explained that brand companies may create obstacles for generic developers to purchase samples of a brand-name drug.

“In general, generic drug developers need the samples of the brand drug to develop their generic product and/or to conduct testing to show that their product is bioequivalent to the brand drug for FDA approval,” he said.

“Without these samples, generic drug makers may not be able to develop generic alternatives. Yet the FDA has heard that some brand companies will adopt tactics to make it hard for the generic companies to purchase these brand drugs at a fair value and in the open marketplace.”

One such tactic is for brand companies to place restrictions in their commercial contracts or agreements with prescription drug distributors, wholesalers, or specialty pharmacies that limit their ability to sell samples to generic drug developers.

In other cases, brand companies may be preventing generic drug developers from accessing samples due to limited distribution programs required by a Risk Evaluation and Mitigation Strategy (REMS) with Elements to Assure Safe Use (ETASU).

“But I want to be very clear: a path to securing samples of brand drugs for the purpose of generic drug development should always be available,” Dr Gottlieb said. “Even in the case of limited distribution programs, such as those required by certain REMS, there should be a path forward for generic drug development.”

With this in mind, the FDA has released a list of brand companies that may have prevented generic drug developers from accessing samples. The list contains 52 brand-name drugs, including Pomalyst, Promacta, Revlimid, Tasigna, and Thalidomid.

Generic drug developers have reported trouble obtaining samples of these drugs and asked the FDA for assistance.

When the FDA receives such a request, the agency first determines whether the product in question has a REMS program with ETASU that may impact distribution.

If the FDA confirms the existence of such a program, the generic company can submit its bioequivalence testing protocol to the FDA. The agency then evaluates this protocol to ensure the plan for testing the product contains safety protections comparable to the brand product’s REMS program.

If a generic developer’s plans include appropriate protections, the developer can request that the FDA send a Safety Determination Letter to the brand company. This letter notes that the REMS program doesn’t prevent the brand company from selling its product to generic drug developers.

The FDA has issued 21 Safety Determination Letters to date, according to Dr Gottlieb.

If a generic drug developer has trouble obtaining samples of a drug for which there is no REMS program with ETASU, the FDA informs the developer that there are no FDA-required restrictions that would prevent it from obtaining samples.

The FDA also notifies the Federal Trade Commission (FTC) of requests from generic drug developers seeking assistance in obtaining samples from brand companies. And the FDA encourages generic drug developers to raise these cases with the FTC if they believe that anticompetitive conduct has taken place.

Red blood cells

The US Food and Drug Administration (FDA) has approved epoetin alfa-epbx (Retacrit), a biosimilar to epoetin alfa (Epogen/Procrit).

Epoetin alfa-epbx is approved for the treatment of anemia caused by chronic kidney disease, the use of zidovudine in patients with HIV infection, and myelosuppressive chemotherapy in patients who have a minimum of 2 additional months of planned chemotherapy.

Epoetin alfa-epbx is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during elective, noncardiac, or nonvascular surgery.

As with epoetin alfa, the prescribing information for epoetin alfa-epbx contains a Boxed Warning noting that erythropoiesis-stimulating agents increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.

The FDA granted approval of epoetin alfa-epbx to Hospira Inc., a Pfizer company.

The agency’s approval is based on a review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

This evidence is available in an FDA briefing document on the biologics license application for epoetin alfa-epbx.

Red blood cells

The US Food and Drug Administration (FDA) has approved epoetin alfa-epbx (Retacrit), a biosimilar to epoetin alfa (Epogen/Procrit).

Epoetin alfa-epbx is approved for the treatment of anemia caused by chronic kidney disease, the use of zidovudine in patients with HIV infection, and myelosuppressive chemotherapy in patients who have a minimum of 2 additional months of planned chemotherapy.

Epoetin alfa-epbx is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during elective, noncardiac, or nonvascular surgery.

As with epoetin alfa, the prescribing information for epoetin alfa-epbx contains a Boxed Warning noting that erythropoiesis-stimulating agents increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.

The FDA granted approval of epoetin alfa-epbx to Hospira Inc., a Pfizer company.

The agency’s approval is based on a review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

This evidence is available in an FDA briefing document on the biologics license application for epoetin alfa-epbx.

Red blood cells

The US Food and Drug Administration (FDA) has approved epoetin alfa-epbx (Retacrit), a biosimilar to epoetin alfa (Epogen/Procrit).

Epoetin alfa-epbx is approved for the treatment of anemia caused by chronic kidney disease, the use of zidovudine in patients with HIV infection, and myelosuppressive chemotherapy in patients who have a minimum of 2 additional months of planned chemotherapy.

Epoetin alfa-epbx is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during elective, noncardiac, or nonvascular surgery.

As with epoetin alfa, the prescribing information for epoetin alfa-epbx contains a Boxed Warning noting that erythropoiesis-stimulating agents increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.

The FDA granted approval of epoetin alfa-epbx to Hospira Inc., a Pfizer company.

The agency’s approval is based on a review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

This evidence is available in an FDA briefing document on the biologics license application for epoetin alfa-epbx.

Micrograph showing MM

The US Food and Drug Administration (FDA) has granted orphan drug designation to galinpepimut-S (GPS) as a treatment for multiple myeloma (MM).

GPS is an immunotherapeutic that targets malignancies characterized by overexpression of the Wilms tumor 1 (WT1) antigen.

GPS consists of 4 peptide chains, 2 of which are modified chains that induce an innate immune response (CD4+/CD8+) against the WT1 antigen and access a range of HLA types.

When GPS is administered to a patient, the induced immune response has the potential to recognize and destroy cancer cells and provide ongoing support to the immune system so it can continue to target and destroy residual cancer cells.

GPS also has orphan designation from the FDA for the treatment of acute myeloid leukemia and malignant plural mesothelioma.

Phase 2 trial

GPS has been investigated in a phase 2 trial of MM patients. Results from this trial were recently presented at the 44th Annual Meeting of the EBMT.

Researchers evaluated GPS in combination with lenalidomide as maintenance therapy in MM patients who received an autologous stem cell transplant (ASCT).

The study enrolled 19 patients who began receiving GPS within 22 days of ASCT. They received 6 doses every 2 weeks. (Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor.)

Patients received 6 additional monthly doses of GPS as well as lenalidomide maintenance (10 mg daily) starting on day 100 post-ASCT.

Twelve patients received all 12 doses of GPS. Eleven patients achieved a complete response or very good partial response. All of these patients had CD4 immune responses, and 9 of them had CD8 immune responses.

The progression-free survival was 81% at 12 months and 62% at 18 months. The median progression-free survival was 23.6 months (range, 15.2 to not reached).

The overall survival was 88% at 18 months, and the median overall survival was not reached.

About orphan designation

The FDA grants orphan designation to products 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.

Micrograph showing MM

The US Food and Drug Administration (FDA) has granted orphan drug designation to galinpepimut-S (GPS) as a treatment for multiple myeloma (MM).

GPS is an immunotherapeutic that targets malignancies characterized by overexpression of the Wilms tumor 1 (WT1) antigen.

GPS consists of 4 peptide chains, 2 of which are modified chains that induce an innate immune response (CD4+/CD8+) against the WT1 antigen and access a range of HLA types.

When GPS is administered to a patient, the induced immune response has the potential to recognize and destroy cancer cells and provide ongoing support to the immune system so it can continue to target and destroy residual cancer cells.

GPS also has orphan designation from the FDA for the treatment of acute myeloid leukemia and malignant plural mesothelioma.

Phase 2 trial

GPS has been investigated in a phase 2 trial of MM patients. Results from this trial were recently presented at the 44th Annual Meeting of the EBMT.

Researchers evaluated GPS in combination with lenalidomide as maintenance therapy in MM patients who received an autologous stem cell transplant (ASCT).

The study enrolled 19 patients who began receiving GPS within 22 days of ASCT. They received 6 doses every 2 weeks. (Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor.)

Patients received 6 additional monthly doses of GPS as well as lenalidomide maintenance (10 mg daily) starting on day 100 post-ASCT.

Twelve patients received all 12 doses of GPS. Eleven patients achieved a complete response or very good partial response. All of these patients had CD4 immune responses, and 9 of them had CD8 immune responses.

The progression-free survival was 81% at 12 months and 62% at 18 months. The median progression-free survival was 23.6 months (range, 15.2 to not reached).

The overall survival was 88% at 18 months, and the median overall survival was not reached.

About orphan designation

The FDA grants orphan designation to products 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.

Micrograph showing MM

The US Food and Drug Administration (FDA) has granted orphan drug designation to galinpepimut-S (GPS) as a treatment for multiple myeloma (MM).

GPS is an immunotherapeutic that targets malignancies characterized by overexpression of the Wilms tumor 1 (WT1) antigen.

GPS consists of 4 peptide chains, 2 of which are modified chains that induce an innate immune response (CD4+/CD8+) against the WT1 antigen and access a range of HLA types.

When GPS is administered to a patient, the induced immune response has the potential to recognize and destroy cancer cells and provide ongoing support to the immune system so it can continue to target and destroy residual cancer cells.

GPS also has orphan designation from the FDA for the treatment of acute myeloid leukemia and malignant plural mesothelioma.

Phase 2 trial

GPS has been investigated in a phase 2 trial of MM patients. Results from this trial were recently presented at the 44th Annual Meeting of the EBMT.

Researchers evaluated GPS in combination with lenalidomide as maintenance therapy in MM patients who received an autologous stem cell transplant (ASCT).

The study enrolled 19 patients who began receiving GPS within 22 days of ASCT. They received 6 doses every 2 weeks. (Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor.)

Patients received 6 additional monthly doses of GPS as well as lenalidomide maintenance (10 mg daily) starting on day 100 post-ASCT.

Twelve patients received all 12 doses of GPS. Eleven patients achieved a complete response or very good partial response. All of these patients had CD4 immune responses, and 9 of them had CD8 immune responses.

The progression-free survival was 81% at 12 months and 62% at 18 months. The median progression-free survival was 23.6 months (range, 15.2 to not reached).

The overall survival was 88% at 18 months, and the median overall survival was not reached.

About orphan designation

The FDA grants orphan designation to products 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.

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted another approval for the CD38-directed antibody daratumumab (Darzalex®).

Daratumumab is now approved for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

Daratumumab was first approved by the FDA in 2015 as a monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.

In 2016, daratumumab was approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat MM patients who have received at least 1 prior therapy.

In 2017, daratumumab was approved for use in combination with pomalidomide and dexamethasone to treat MM patients who have received at least 2 prior therapies, including lenalidomide and a PI.

For full prescribing information, visit www.darzalex.com.

Phase 3 trial

The FDA’s approval of daratumumab in combination with VMP is supported by data from the phase 3 ALCYONE (MMY3007) study. Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. And rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to AEs was 5% in the D-VMP arm and 9% in the VMP arm.

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted another approval for the CD38-directed antibody daratumumab (Darzalex®).

Daratumumab is now approved for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

Daratumumab was first approved by the FDA in 2015 as a monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.

In 2016, daratumumab was approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat MM patients who have received at least 1 prior therapy.

In 2017, daratumumab was approved for use in combination with pomalidomide and dexamethasone to treat MM patients who have received at least 2 prior therapies, including lenalidomide and a PI.

For full prescribing information, visit www.darzalex.com.

Phase 3 trial

The FDA’s approval of daratumumab in combination with VMP is supported by data from the phase 3 ALCYONE (MMY3007) study. Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. And rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to AEs was 5% in the D-VMP arm and 9% in the VMP arm.

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted another approval for the CD38-directed antibody daratumumab (Darzalex®).

Daratumumab is now approved for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

Daratumumab was first approved by the FDA in 2015 as a monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.

In 2016, daratumumab was approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat MM patients who have received at least 1 prior therapy.

In 2017, daratumumab was approved for use in combination with pomalidomide and dexamethasone to treat MM patients who have received at least 2 prior therapies, including lenalidomide and a PI.

For full prescribing information, visit www.darzalex.com.

Phase 3 trial

The FDA’s approval of daratumumab in combination with VMP is supported by data from the phase 3 ALCYONE (MMY3007) study. Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. And rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to AEs was 5% in the D-VMP arm and 9% in the VMP arm.

Photo by Patrick Pelletier

The availability of generic imatinib has had limited effects on costs of the drug, according to research published in Health Affairs.

Data suggest the cost of Gleevec in the US has more than doubled since the drug was approved in 2001, and the introduction of generic imatinib has reduced costs only slightly.

Two years after generic imatinib hit the market, a month’s supply of Gleevec cost about $9000, and the cost for generic imatinib was about $8000.

“Patients and providers have all looked forward to generic entry, expecting major price reductions,” said study author Stacie Dusetzina, PhD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“Unfortunately, we don’t see prices drop as quickly and as low as we would hope when generics are available.”

For this study, Dr Dusetzina and a colleague analyzed data from the MarketScan Commercial Research Database. The database contained records of 139,233 prescription fills for imatinib, which were made by 7201 patients from May 2001 through September 2017.

The researchers noted that Gleevec was priced at nearly $4000 for a 1-month (400 mg) supply when it came on the market in 2001. That price escalated to nearly $10,000 by 2015 before a generic competitor entered the market.

However, prices for Gleevec and generic imatinib remained high 2 years later. In 2017, a month’s supply of Gleevec cost about $9000, and the cost of generic imatinib was about $8000.

The researchers said the Gleevec case demonstrates several potential barriers to effective generic price competition, including shifts in prescribing toward more expensive brand-name treatments and smaller-than-expected price reductions.

Twenty-four percent of imatinib (Gleevec) prescriptions claims were for “dispense as written,” according to the researchers. This suggests that patients or providers specifically wanted to stay on the brand-name drug instead of switching to the generic.

“The more than doubling of the drug price over time and the lack of price reductions observed with nearly 2 years of generic drug competition is concerning,” Dr Dusetzina said.

“It begs the question whether we can rely on generic entry as a primary approach to address drug pricing for high-priced specialty medications. We need robust competition to move prices in this space.”

Photo by Patrick Pelletier

The availability of generic imatinib has had limited effects on costs of the drug, according to research published in Health Affairs.

Data suggest the cost of Gleevec in the US has more than doubled since the drug was approved in 2001, and the introduction of generic imatinib has reduced costs only slightly.

Two years after generic imatinib hit the market, a month’s supply of Gleevec cost about $9000, and the cost for generic imatinib was about $8000.

“Patients and providers have all looked forward to generic entry, expecting major price reductions,” said study author Stacie Dusetzina, PhD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“Unfortunately, we don’t see prices drop as quickly and as low as we would hope when generics are available.”

For this study, Dr Dusetzina and a colleague analyzed data from the MarketScan Commercial Research Database. The database contained records of 139,233 prescription fills for imatinib, which were made by 7201 patients from May 2001 through September 2017.

The researchers noted that Gleevec was priced at nearly $4000 for a 1-month (400 mg) supply when it came on the market in 2001. That price escalated to nearly $10,000 by 2015 before a generic competitor entered the market.

However, prices for Gleevec and generic imatinib remained high 2 years later. In 2017, a month’s supply of Gleevec cost about $9000, and the cost of generic imatinib was about $8000.

The researchers said the Gleevec case demonstrates several potential barriers to effective generic price competition, including shifts in prescribing toward more expensive brand-name treatments and smaller-than-expected price reductions.

Twenty-four percent of imatinib (Gleevec) prescriptions claims were for “dispense as written,” according to the researchers. This suggests that patients or providers specifically wanted to stay on the brand-name drug instead of switching to the generic.

“The more than doubling of the drug price over time and the lack of price reductions observed with nearly 2 years of generic drug competition is concerning,” Dr Dusetzina said.

“It begs the question whether we can rely on generic entry as a primary approach to address drug pricing for high-priced specialty medications. We need robust competition to move prices in this space.”

Photo by Patrick Pelletier

The availability of generic imatinib has had limited effects on costs of the drug, according to research published in Health Affairs.

Data suggest the cost of Gleevec in the US has more than doubled since the drug was approved in 2001, and the introduction of generic imatinib has reduced costs only slightly.

Two years after generic imatinib hit the market, a month’s supply of Gleevec cost about $9000, and the cost for generic imatinib was about $8000.

“Patients and providers have all looked forward to generic entry, expecting major price reductions,” said study author Stacie Dusetzina, PhD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“Unfortunately, we don’t see prices drop as quickly and as low as we would hope when generics are available.”

For this study, Dr Dusetzina and a colleague analyzed data from the MarketScan Commercial Research Database. The database contained records of 139,233 prescription fills for imatinib, which were made by 7201 patients from May 2001 through September 2017.

The researchers noted that Gleevec was priced at nearly $4000 for a 1-month (400 mg) supply when it came on the market in 2001. That price escalated to nearly $10,000 by 2015 before a generic competitor entered the market.

However, prices for Gleevec and generic imatinib remained high 2 years later. In 2017, a month’s supply of Gleevec cost about $9000, and the cost of generic imatinib was about $8000.

The researchers said the Gleevec case demonstrates several potential barriers to effective generic price competition, including shifts in prescribing toward more expensive brand-name treatments and smaller-than-expected price reductions.

Twenty-four percent of imatinib (Gleevec) prescriptions claims were for “dispense as written,” according to the researchers. This suggests that patients or providers specifically wanted to stay on the brand-name drug instead of switching to the generic.

“The more than doubling of the drug price over time and the lack of price reductions observed with nearly 2 years of generic drug competition is concerning,” Dr Dusetzina said.

“It begs the question whether we can rely on generic entry as a primary approach to address drug pricing for high-priced specialty medications. We need robust competition to move prices in this space.”