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FDA approves first treatment for primary HLH
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
Eltrombopag approved as first-line SAA therapy
The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).
Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.
Eltrombopag received breakthrough therapy designation and priority review for this indication.
Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.
The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.
Updated results from the trial are available in the prescribing information for eltrombopag.
The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.
The starting dose of eltrombopag was:
- 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
- 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
- 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).
Patients were divided into three cohorts with different dosing schedules.
The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.
Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.
The median duration of both overall and complete response was 24.3 months.
The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).
Eltrombopag is a product of Novartis.
The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).
Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.
Eltrombopag received breakthrough therapy designation and priority review for this indication.
Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.
The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.
Updated results from the trial are available in the prescribing information for eltrombopag.
The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.
The starting dose of eltrombopag was:
- 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
- 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
- 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).
Patients were divided into three cohorts with different dosing schedules.
The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.
Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.
The median duration of both overall and complete response was 24.3 months.
The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).
Eltrombopag is a product of Novartis.
The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).
Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.
Eltrombopag received breakthrough therapy designation and priority review for this indication.
Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.
The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.
Updated results from the trial are available in the prescribing information for eltrombopag.
The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.
The starting dose of eltrombopag was:
- 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
- 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
- 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).
Patients were divided into three cohorts with different dosing schedules.
The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.
Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.
The median duration of both overall and complete response was 24.3 months.
The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).
Eltrombopag is a product of Novartis.
Quick FDA approval for brentuximab vedotin in PTCL
The U.S. Food and Drug Administration (FDA) has approved a new indication for brentuximab vedotin (ADCETRIS®) less than 2 weeks after receiving the completed supplemental biologics license application (sBLA).
Brentuximab vedotin is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) to treat adults with previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
The FDA granted priority review and breakthrough therapy designation to the sBLA for brentuximab vedotin in this indication.
The FDA reviewed the sBLA under the Real-Time Oncology Review Pilot Program, which led to approval less than 2 weeks after the application was submitted in full.
“The Real-Time Oncology Review program allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.
“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review.”
Trial data
The FDA’s approval is based on results from the phase 3 ECHELON-2 trial (NCT01777152).
Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced results from this trial last month. Additional results are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 997).
The trial enrolled 452 patients with CD30-positive PTCL. The patients were randomized to receive brentuximab vedotin (BV) plus CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
The objective response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.003). The complete response rate was 68% and 56%, respectively (P=0.007).
Progression-free survival was significantly better in the BV-CHP arm than in the CHOP arm (hazard ratio=0.71; P=0.011), as was overall survival (hazard ratio=0.66; P=0.024).
The most common adverse events of any grade that occurred in at least 20% of patients in the BV-CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia.
Serious adverse events occurring in at least 2% of patients in the BV-CHP arm included febrile neutropenia, pneumonia, pyrexia, and sepsis.
Results of this trial suggest prophylactic growth factors should be given to previously untreated PTCL patients receiving BV-CHP (starting at cycle 1).
The U.S. Food and Drug Administration (FDA) has approved a new indication for brentuximab vedotin (ADCETRIS®) less than 2 weeks after receiving the completed supplemental biologics license application (sBLA).
Brentuximab vedotin is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) to treat adults with previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
The FDA granted priority review and breakthrough therapy designation to the sBLA for brentuximab vedotin in this indication.
The FDA reviewed the sBLA under the Real-Time Oncology Review Pilot Program, which led to approval less than 2 weeks after the application was submitted in full.
“The Real-Time Oncology Review program allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.
“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review.”
Trial data
The FDA’s approval is based on results from the phase 3 ECHELON-2 trial (NCT01777152).
Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced results from this trial last month. Additional results are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 997).
The trial enrolled 452 patients with CD30-positive PTCL. The patients were randomized to receive brentuximab vedotin (BV) plus CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
The objective response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.003). The complete response rate was 68% and 56%, respectively (P=0.007).
Progression-free survival was significantly better in the BV-CHP arm than in the CHOP arm (hazard ratio=0.71; P=0.011), as was overall survival (hazard ratio=0.66; P=0.024).
The most common adverse events of any grade that occurred in at least 20% of patients in the BV-CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia.
Serious adverse events occurring in at least 2% of patients in the BV-CHP arm included febrile neutropenia, pneumonia, pyrexia, and sepsis.
Results of this trial suggest prophylactic growth factors should be given to previously untreated PTCL patients receiving BV-CHP (starting at cycle 1).
The U.S. Food and Drug Administration (FDA) has approved a new indication for brentuximab vedotin (ADCETRIS®) less than 2 weeks after receiving the completed supplemental biologics license application (sBLA).
Brentuximab vedotin is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) to treat adults with previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
The FDA granted priority review and breakthrough therapy designation to the sBLA for brentuximab vedotin in this indication.
The FDA reviewed the sBLA under the Real-Time Oncology Review Pilot Program, which led to approval less than 2 weeks after the application was submitted in full.
“The Real-Time Oncology Review program allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.
“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review.”
Trial data
The FDA’s approval is based on results from the phase 3 ECHELON-2 trial (NCT01777152).
Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced results from this trial last month. Additional results are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 997).
The trial enrolled 452 patients with CD30-positive PTCL. The patients were randomized to receive brentuximab vedotin (BV) plus CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
The objective response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.003). The complete response rate was 68% and 56%, respectively (P=0.007).
Progression-free survival was significantly better in the BV-CHP arm than in the CHOP arm (hazard ratio=0.71; P=0.011), as was overall survival (hazard ratio=0.66; P=0.024).
The most common adverse events of any grade that occurred in at least 20% of patients in the BV-CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia.
Serious adverse events occurring in at least 2% of patients in the BV-CHP arm included febrile neutropenia, pneumonia, pyrexia, and sepsis.
Results of this trial suggest prophylactic growth factors should be given to previously untreated PTCL patients receiving BV-CHP (starting at cycle 1).
FDA approves generic drugs for APL
The U.S. Food and Drug Administration (FDA) has now approved three generic arsenic trioxide products for use in patients with acute promyelocytic leukemia (APL).
Two of the products—from Zydus Cadila and Amring Pharmaceuticals—were approved on November 13.
The third—from Fresenius Kabi—was approved in August and launched in the United States last month.
All three injectable arsenic trioxide products (1 mg/mL) are generic versions of Teva’s Trisenox.
Since 2000, Trisenox has been FDA-approved to induce remission and as consolidation therapy for patients with APL who are refractory to, or have relapsed after, retinoid and anthracycline chemotherapy, and whose APL is characterized by presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
In January, the FDA approved Trisenox for use in combination with tretinoin to treat adults with newly diagnosed, low-risk APL with the t(15;17) translocation or PML/RAR-alpha gene expression.
The U.S. Food and Drug Administration (FDA) has now approved three generic arsenic trioxide products for use in patients with acute promyelocytic leukemia (APL).
Two of the products—from Zydus Cadila and Amring Pharmaceuticals—were approved on November 13.
The third—from Fresenius Kabi—was approved in August and launched in the United States last month.
All three injectable arsenic trioxide products (1 mg/mL) are generic versions of Teva’s Trisenox.
Since 2000, Trisenox has been FDA-approved to induce remission and as consolidation therapy for patients with APL who are refractory to, or have relapsed after, retinoid and anthracycline chemotherapy, and whose APL is characterized by presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
In January, the FDA approved Trisenox for use in combination with tretinoin to treat adults with newly diagnosed, low-risk APL with the t(15;17) translocation or PML/RAR-alpha gene expression.
The U.S. Food and Drug Administration (FDA) has now approved three generic arsenic trioxide products for use in patients with acute promyelocytic leukemia (APL).
Two of the products—from Zydus Cadila and Amring Pharmaceuticals—were approved on November 13.
The third—from Fresenius Kabi—was approved in August and launched in the United States last month.
All three injectable arsenic trioxide products (1 mg/mL) are generic versions of Teva’s Trisenox.
Since 2000, Trisenox has been FDA-approved to induce remission and as consolidation therapy for patients with APL who are refractory to, or have relapsed after, retinoid and anthracycline chemotherapy, and whose APL is characterized by presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
In January, the FDA approved Trisenox for use in combination with tretinoin to treat adults with newly diagnosed, low-risk APL with the t(15;17) translocation or PML/RAR-alpha gene expression.
FDA approves elotuzumab combo for rel/ref MM
The U.S. Food and Drug Administration (FDA) has approved elotuzumab (Empliciti®) in combination with pomalidomide and dexamethasone.
The combination is now approved for use in adults with multiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is also FDA-approved in combination with lenalidomide and dexamethasone to treat adult MM patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from the phase 2 ELOQUENT-3 trial, which were presented at the 23rd Congress of the European Hematology Association in June.
ELOQUENT-3 enrolled MM patients who had refractory or relapsed and refractory MM and had received both lenalidomide and a proteasome inhibitor.
The patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n=60) or pomalidomide and dexamethasone (Pd, n=57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P=0.0029). The rate of complete response or stringent complete response was 8.3% in the EPd arm and 1.8% in the Pd arm.
The median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (hazard ratio=0.54, P=0.0078).
Serious adverse events (AEs) occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious AEs (in the EPd and Pd arms, respectively) were pneumonia (13% and 11%) and respiratory tract infection (7% and 3.6%).
AEs occurring in at least 10% of patients in the EPd arm and at least 5% of those in the Pd arm (respectively) included:
- Constipation (22% and 11%)
- Hyperglycemia (20% and 15%)
- Pneumonia (18% and 13%)
- Diarrhea (18% and 9%)
- Respiratory tract infection (17% and 9%)
- Bone pain (15% and 9%)
- Dyspnea (15% and 7%)
- Muscle spasms (13% and 5%)
- Peripheral edema (13% and 7%)
- Lymphopenia (10% and 1.8%).
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available at www.empliciti.com.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The U.S. Food and Drug Administration (FDA) has approved elotuzumab (Empliciti®) in combination with pomalidomide and dexamethasone.
The combination is now approved for use in adults with multiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is also FDA-approved in combination with lenalidomide and dexamethasone to treat adult MM patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from the phase 2 ELOQUENT-3 trial, which were presented at the 23rd Congress of the European Hematology Association in June.
ELOQUENT-3 enrolled MM patients who had refractory or relapsed and refractory MM and had received both lenalidomide and a proteasome inhibitor.
The patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n=60) or pomalidomide and dexamethasone (Pd, n=57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P=0.0029). The rate of complete response or stringent complete response was 8.3% in the EPd arm and 1.8% in the Pd arm.
The median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (hazard ratio=0.54, P=0.0078).
Serious adverse events (AEs) occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious AEs (in the EPd and Pd arms, respectively) were pneumonia (13% and 11%) and respiratory tract infection (7% and 3.6%).
AEs occurring in at least 10% of patients in the EPd arm and at least 5% of those in the Pd arm (respectively) included:
- Constipation (22% and 11%)
- Hyperglycemia (20% and 15%)
- Pneumonia (18% and 13%)
- Diarrhea (18% and 9%)
- Respiratory tract infection (17% and 9%)
- Bone pain (15% and 9%)
- Dyspnea (15% and 7%)
- Muscle spasms (13% and 5%)
- Peripheral edema (13% and 7%)
- Lymphopenia (10% and 1.8%).
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available at www.empliciti.com.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The U.S. Food and Drug Administration (FDA) has approved elotuzumab (Empliciti®) in combination with pomalidomide and dexamethasone.
The combination is now approved for use in adults with multiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is also FDA-approved in combination with lenalidomide and dexamethasone to treat adult MM patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from the phase 2 ELOQUENT-3 trial, which were presented at the 23rd Congress of the European Hematology Association in June.
ELOQUENT-3 enrolled MM patients who had refractory or relapsed and refractory MM and had received both lenalidomide and a proteasome inhibitor.
The patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n=60) or pomalidomide and dexamethasone (Pd, n=57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P=0.0029). The rate of complete response or stringent complete response was 8.3% in the EPd arm and 1.8% in the Pd arm.
The median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (hazard ratio=0.54, P=0.0078).
Serious adverse events (AEs) occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious AEs (in the EPd and Pd arms, respectively) were pneumonia (13% and 11%) and respiratory tract infection (7% and 3.6%).
AEs occurring in at least 10% of patients in the EPd arm and at least 5% of those in the Pd arm (respectively) included:
- Constipation (22% and 11%)
- Hyperglycemia (20% and 15%)
- Pneumonia (18% and 13%)
- Diarrhea (18% and 9%)
- Respiratory tract infection (17% and 9%)
- Bone pain (15% and 9%)
- Dyspnea (15% and 7%)
- Muscle spasms (13% and 5%)
- Peripheral edema (13% and 7%)
- Lymphopenia (10% and 1.8%).
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available at www.empliciti.com.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
FDA and EC approve pegfilgrastim biosimilar
The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).
Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.
Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”
The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”
The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.
The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).
Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.
“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.
“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”
The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).
Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.
Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”
The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”
The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.
The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).
Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.
“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.
“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”
The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).
Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.
Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”
The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”
The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.
The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).
Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.
“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.
“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”
Health Canada approves pralatrexate for rel/ref PTCL
Health Canada has granted conditional approval for pralatrexate (Folotyn®) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Pralatrexate received a Notice of Compliance with Conditions (NOC/c), which is an approval granted on the basis of promising evidence of clinical effectiveness that must be verified in additional clinical trials.
To be approved under Health Canada’s NOC/c policy, a product must be intended for the treatment, prevention, or diagnosis of a serious, life-threatening, or severely debilitating illness.
In addition, the product must have demonstrated promising benefit, be of high quality, have an acceptable safety profile based on a benefit/risk assessment, and either respond to a serious unmet need or provide a significant improvement over existing therapies.
The NOC/c for pralatrexate is based on response rates in the single-arm, phase 2 PROPEL trial. Results from PROPEL were published in the Journal of Clinical Oncology in 2011.
The trial enrolled 115 patients with relapsed or refractory PTCL who had received a median of three (range, 1-12) prior systemic therapies.
The patients received pralatrexate once weekly at a dose of 30 mg/m2 for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity.
In the 109 evaluable patients, the response rate was 29% (32/109). The complete response rate was 11% (n=12), and the partial response rate was 18% (n=20).
The median duration of response was 10.1 months, the median progression-free survival was 3.5 months, and the median overall survival was 14.5 months.
The most common adverse events (AEs) were mucositis (71%), thrombocytopenia (41%), nausea (41%), fatigue (36%), pyrexia (34%), anemia (34%), constipation (34%), edema (31%), cough (29%), epistaxis (26%), vomiting (25%), neutropenia (25%), and diarrhea (23%).
The most common grade 3/4 AEs were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%).
The product monograph for pralatrexate contains a boxed warning highlighting the risk of AEs associated with pralatrexate use, including dermatologic reactions, bone marrow suppression, infection, mucosal inflammation, tumor lysis syndrome, potential fetal harm, and pulmonary toxicity.
The product monograph is available for download from the website of Servier Canada, the company marketing pralatrexate in Canada.
Health Canada has granted conditional approval for pralatrexate (Folotyn®) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Pralatrexate received a Notice of Compliance with Conditions (NOC/c), which is an approval granted on the basis of promising evidence of clinical effectiveness that must be verified in additional clinical trials.
To be approved under Health Canada’s NOC/c policy, a product must be intended for the treatment, prevention, or diagnosis of a serious, life-threatening, or severely debilitating illness.
In addition, the product must have demonstrated promising benefit, be of high quality, have an acceptable safety profile based on a benefit/risk assessment, and either respond to a serious unmet need or provide a significant improvement over existing therapies.
The NOC/c for pralatrexate is based on response rates in the single-arm, phase 2 PROPEL trial. Results from PROPEL were published in the Journal of Clinical Oncology in 2011.
The trial enrolled 115 patients with relapsed or refractory PTCL who had received a median of three (range, 1-12) prior systemic therapies.
The patients received pralatrexate once weekly at a dose of 30 mg/m2 for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity.
In the 109 evaluable patients, the response rate was 29% (32/109). The complete response rate was 11% (n=12), and the partial response rate was 18% (n=20).
The median duration of response was 10.1 months, the median progression-free survival was 3.5 months, and the median overall survival was 14.5 months.
The most common adverse events (AEs) were mucositis (71%), thrombocytopenia (41%), nausea (41%), fatigue (36%), pyrexia (34%), anemia (34%), constipation (34%), edema (31%), cough (29%), epistaxis (26%), vomiting (25%), neutropenia (25%), and diarrhea (23%).
The most common grade 3/4 AEs were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%).
The product monograph for pralatrexate contains a boxed warning highlighting the risk of AEs associated with pralatrexate use, including dermatologic reactions, bone marrow suppression, infection, mucosal inflammation, tumor lysis syndrome, potential fetal harm, and pulmonary toxicity.
The product monograph is available for download from the website of Servier Canada, the company marketing pralatrexate in Canada.
Health Canada has granted conditional approval for pralatrexate (Folotyn®) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Pralatrexate received a Notice of Compliance with Conditions (NOC/c), which is an approval granted on the basis of promising evidence of clinical effectiveness that must be verified in additional clinical trials.
To be approved under Health Canada’s NOC/c policy, a product must be intended for the treatment, prevention, or diagnosis of a serious, life-threatening, or severely debilitating illness.
In addition, the product must have demonstrated promising benefit, be of high quality, have an acceptable safety profile based on a benefit/risk assessment, and either respond to a serious unmet need or provide a significant improvement over existing therapies.
The NOC/c for pralatrexate is based on response rates in the single-arm, phase 2 PROPEL trial. Results from PROPEL were published in the Journal of Clinical Oncology in 2011.
The trial enrolled 115 patients with relapsed or refractory PTCL who had received a median of three (range, 1-12) prior systemic therapies.
The patients received pralatrexate once weekly at a dose of 30 mg/m2 for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity.
In the 109 evaluable patients, the response rate was 29% (32/109). The complete response rate was 11% (n=12), and the partial response rate was 18% (n=20).
The median duration of response was 10.1 months, the median progression-free survival was 3.5 months, and the median overall survival was 14.5 months.
The most common adverse events (AEs) were mucositis (71%), thrombocytopenia (41%), nausea (41%), fatigue (36%), pyrexia (34%), anemia (34%), constipation (34%), edema (31%), cough (29%), epistaxis (26%), vomiting (25%), neutropenia (25%), and diarrhea (23%).
The most common grade 3/4 AEs were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%).
The product monograph for pralatrexate contains a boxed warning highlighting the risk of AEs associated with pralatrexate use, including dermatologic reactions, bone marrow suppression, infection, mucosal inflammation, tumor lysis syndrome, potential fetal harm, and pulmonary toxicity.
The product monograph is available for download from the website of Servier Canada, the company marketing pralatrexate in Canada.
EC approves venetoclax in combo with rituximab
The European Commission (EC) has approved a new indication for venetoclax (Venclyxto®).
The drug is now approved for use in combination with rituximab to treat patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
The approval is valid in all member states of the European Union as well as Iceland, Liechtenstein, and Norway.
The EC’s approval is based on results from the phase 3 MURANO trial, which were published in The New England Journal of Medicine in March.
The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.
According to an independent review committee, the overall response rate was 92.3% in the VEN+R arm and 72.3% in the B+R arm. The investigator-assessed overall response rates were 93.3% and 67.7%, respectively.
According to investigators, the median progression-free survival (PFS) was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio [HR]=0.17; P<0.0001).
According to the independent review committee, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (HR=0.20; P<0.0001).
Investigators said the 2-year PFS rate was 84.9% in the VEN+R arm and 36.3% in the B+R arm.
They said the 2-year overall survival rates were 91.9% and 86.6%, respectively (HR=0.48; P<0.0001). The median overall survival was not reached in either arm.
Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment arms (in the VEN+R and B+R arms, respectively) included:
- Neutropenia (57.7% and 38.8%)
- Infections and infestations (17.5% and 21.8%)
- Anemia (10.8% and 13.8%)
- Thrombocytopenia (5.7% and 10.1%)
- Febrile neutropenia (3.6% and 9.6%)
- Pneumonia (5.2% and 8.0%)
- Infusion-related reactions (1.5% and 5.3%)
- Tumor lysis syndrome (3.1% and 1.1%)
- Hypotension (0% and 2.7%)
- Hyperglycemia (2.1% and 0%)
- Hypogammaglobulinemia (2.1% and 0%).
Serious AEs with at least a 2% difference in incidence between the arms (in the VEN+R and B+R arms, respectively) were:
- Pneumonia (8.2% and 8.0%)
- Febrile neutropenia (3.6% and 8.5%)
- Pyrexia (2.6% and 6.9%)
- Anemia (1.5% and 2.7%)
- Infusion-related reactions (0.5% and 3.2%)
- Sepsis (0.5% and 2.1%)
- Tumor lysis syndrome (2.1% and 0.5%)
- Hypotension (0% and 2.7%).
Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.
Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter’s transformation.
The European Commission (EC) has approved a new indication for venetoclax (Venclyxto®).
The drug is now approved for use in combination with rituximab to treat patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
The approval is valid in all member states of the European Union as well as Iceland, Liechtenstein, and Norway.
The EC’s approval is based on results from the phase 3 MURANO trial, which were published in The New England Journal of Medicine in March.
The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.
According to an independent review committee, the overall response rate was 92.3% in the VEN+R arm and 72.3% in the B+R arm. The investigator-assessed overall response rates were 93.3% and 67.7%, respectively.
According to investigators, the median progression-free survival (PFS) was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio [HR]=0.17; P<0.0001).
According to the independent review committee, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (HR=0.20; P<0.0001).
Investigators said the 2-year PFS rate was 84.9% in the VEN+R arm and 36.3% in the B+R arm.
They said the 2-year overall survival rates were 91.9% and 86.6%, respectively (HR=0.48; P<0.0001). The median overall survival was not reached in either arm.
Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment arms (in the VEN+R and B+R arms, respectively) included:
- Neutropenia (57.7% and 38.8%)
- Infections and infestations (17.5% and 21.8%)
- Anemia (10.8% and 13.8%)
- Thrombocytopenia (5.7% and 10.1%)
- Febrile neutropenia (3.6% and 9.6%)
- Pneumonia (5.2% and 8.0%)
- Infusion-related reactions (1.5% and 5.3%)
- Tumor lysis syndrome (3.1% and 1.1%)
- Hypotension (0% and 2.7%)
- Hyperglycemia (2.1% and 0%)
- Hypogammaglobulinemia (2.1% and 0%).
Serious AEs with at least a 2% difference in incidence between the arms (in the VEN+R and B+R arms, respectively) were:
- Pneumonia (8.2% and 8.0%)
- Febrile neutropenia (3.6% and 8.5%)
- Pyrexia (2.6% and 6.9%)
- Anemia (1.5% and 2.7%)
- Infusion-related reactions (0.5% and 3.2%)
- Sepsis (0.5% and 2.1%)
- Tumor lysis syndrome (2.1% and 0.5%)
- Hypotension (0% and 2.7%).
Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.
Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter’s transformation.
The European Commission (EC) has approved a new indication for venetoclax (Venclyxto®).
The drug is now approved for use in combination with rituximab to treat patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
The approval is valid in all member states of the European Union as well as Iceland, Liechtenstein, and Norway.
The EC’s approval is based on results from the phase 3 MURANO trial, which were published in The New England Journal of Medicine in March.
The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.
According to an independent review committee, the overall response rate was 92.3% in the VEN+R arm and 72.3% in the B+R arm. The investigator-assessed overall response rates were 93.3% and 67.7%, respectively.
According to investigators, the median progression-free survival (PFS) was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio [HR]=0.17; P<0.0001).
According to the independent review committee, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (HR=0.20; P<0.0001).
Investigators said the 2-year PFS rate was 84.9% in the VEN+R arm and 36.3% in the B+R arm.
They said the 2-year overall survival rates were 91.9% and 86.6%, respectively (HR=0.48; P<0.0001). The median overall survival was not reached in either arm.
Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment arms (in the VEN+R and B+R arms, respectively) included:
- Neutropenia (57.7% and 38.8%)
- Infections and infestations (17.5% and 21.8%)
- Anemia (10.8% and 13.8%)
- Thrombocytopenia (5.7% and 10.1%)
- Febrile neutropenia (3.6% and 9.6%)
- Pneumonia (5.2% and 8.0%)
- Infusion-related reactions (1.5% and 5.3%)
- Tumor lysis syndrome (3.1% and 1.1%)
- Hypotension (0% and 2.7%)
- Hyperglycemia (2.1% and 0%)
- Hypogammaglobulinemia (2.1% and 0%).
Serious AEs with at least a 2% difference in incidence between the arms (in the VEN+R and B+R arms, respectively) were:
- Pneumonia (8.2% and 8.0%)
- Febrile neutropenia (3.6% and 8.5%)
- Pyrexia (2.6% and 6.9%)
- Anemia (1.5% and 2.7%)
- Infusion-related reactions (0.5% and 3.2%)
- Sepsis (0.5% and 2.1%)
- Tumor lysis syndrome (2.1% and 0.5%)
- Hypotension (0% and 2.7%).
Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.
Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter’s transformation.
Canada approves Jivi for hemophilia A
Health Canada has approved Jivi® (antihemophilic factor [recombinant, B-domain deleted, PEGylated]) for use in patients with hemophilia A.
Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate developed by Bayer.
Health Canada has approved Jivi for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in previously treated hemophilia A patients age 12 and older.
Jivi is also approved for the control and prevention of episodic bleeding and for perioperative management of bleeding.
The recommended initial dosing for Jivi as prophylaxis is twice weekly, with the ability to dose every 5 days and further adjust dosing based on bleeding episodes.
Health Canada’s approval of Jivi is based on the PROTECT VIII trial. Results from this trial are available in the U.S. prescribing information for Jivi.
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, Jivi was used for perioperative management of bleeding.
Efficacy
In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.
Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.
Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).
The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
The median ABR for patients treated on demand was 24.1.
There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.
Safety
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.
Health Canada has approved Jivi® (antihemophilic factor [recombinant, B-domain deleted, PEGylated]) for use in patients with hemophilia A.
Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate developed by Bayer.
Health Canada has approved Jivi for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in previously treated hemophilia A patients age 12 and older.
Jivi is also approved for the control and prevention of episodic bleeding and for perioperative management of bleeding.
The recommended initial dosing for Jivi as prophylaxis is twice weekly, with the ability to dose every 5 days and further adjust dosing based on bleeding episodes.
Health Canada’s approval of Jivi is based on the PROTECT VIII trial. Results from this trial are available in the U.S. prescribing information for Jivi.
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, Jivi was used for perioperative management of bleeding.
Efficacy
In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.
Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.
Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).
The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
The median ABR for patients treated on demand was 24.1.
There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.
Safety
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.
Health Canada has approved Jivi® (antihemophilic factor [recombinant, B-domain deleted, PEGylated]) for use in patients with hemophilia A.
Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate developed by Bayer.
Health Canada has approved Jivi for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in previously treated hemophilia A patients age 12 and older.
Jivi is also approved for the control and prevention of episodic bleeding and for perioperative management of bleeding.
The recommended initial dosing for Jivi as prophylaxis is twice weekly, with the ability to dose every 5 days and further adjust dosing based on bleeding episodes.
Health Canada’s approval of Jivi is based on the PROTECT VIII trial. Results from this trial are available in the U.S. prescribing information for Jivi.
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, Jivi was used for perioperative management of bleeding.
Efficacy
In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.
Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.
Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).
The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
The median ABR for patients treated on demand was 24.1.
There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.
Safety
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.
Weighing the costs of CAR T-cell therapy
The cost-effectiveness of tisagenlecleucel (Kymriah) depends on long-term clinical outcomes, which are presently unknown, according to investigators.
If the long-term outcomes are more modest than clinical trials suggest, then payers may be unwilling to cover the costly therapy, reported John K. Lin, MD, of Stanford University, and his colleagues.
Lowering the price or setting up an outcomes-based pricing structure may be necessary to get insurers to cover the therapy.
Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the U.S. Food and Drug Administration in August 2017 for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL).
In 2018, the FDA expanded the indication for tisagenlecleucel to include adults with relapsed or refractory large B-cell lymphoma, though outcomes from lymphoma trials are not analyzed in the current study.
At a wholesale acquisition cost of $475,000 per infusion, it is the most expensive existing oncology therapy to date, and can be accompanied by expensive, potentially fatal adverse effects.
However, clinical trials suggest that tisagenlecleucel can offer years of relapse-free remission, thereby allowing patients to forgo other expensive therapies such as hematopoietic stem cell transplantation (HSCT).
“Although tisagenlecleucel-induced remission rates are promising, compared with those of established therapies (greater than 80% vs. less than 50%), only short-term follow-up data currently exist,” the investigators wrote in the Journal of Clinical Oncology.
“Given the high cost and broad applicability in other malignancies of tisagenlecleucel, a pressing question for policy makers, payers, patients, and clinicians is whether the cost of therapy represents reasonable value.”
The study used a Markov model to assess various long-term clinical outcome rates and cost thresholds of tisagenlecleucel. The lifetime cost of therapy was assessed and compared with costs of existing therapies.
The results showed that a 5-year relapse free survival rate of 40% would make the present cost ($475,000) of tisagenlecleucel economically reasonable. In this scenario, the increased life expectancy would be 12.1 years and would result in an additional 5.07 quality-adjusted life years (QALY) gained at a cost of $61,000 per QALY, compared with blinatumomab.
But if long-term outcomes are less favorable, tisagenlecleucel becomes much less cost effective. A 5-year relapse-free survival rate of 20% would drop increased life expectancy to 3.8 years, resulting in 1.80 QALYs gained and raising the cost to $151,000 per QALY.
“Our results suggest that at tisagenlecleucel’s current price and payment structure, its economic value is uncertain,” the investigators wrote.
They suggested a price drop to $200,000 or $350,000, which would allow the drug to remain cost effective even in a worse-case scenario, in which patients relapse and tisagenlecleucel is a bridge to transplant.
Another option is to move to outcomes-based pricing. Making payment conditional on 7 months of remission would make the treatment cost effective, according to the analysis.
“Price reductions of tisagenlecleucel or payment only for longer-term remissions would favorably influence cost-effectiveness, even if long-term clinical outcomes are modest,” the investigators wrote.
The study was funded by a Veterans Affairs Office of Academic Affiliations advanced fellowship in health service and research development, and a National Center for Advancing Translational Science Clinical and Translational Science Award.
One of the study coauthors reported consulting and research funding from Novartis.
The cost-effectiveness of tisagenlecleucel (Kymriah) depends on long-term clinical outcomes, which are presently unknown, according to investigators.
If the long-term outcomes are more modest than clinical trials suggest, then payers may be unwilling to cover the costly therapy, reported John K. Lin, MD, of Stanford University, and his colleagues.
Lowering the price or setting up an outcomes-based pricing structure may be necessary to get insurers to cover the therapy.
Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the U.S. Food and Drug Administration in August 2017 for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL).
In 2018, the FDA expanded the indication for tisagenlecleucel to include adults with relapsed or refractory large B-cell lymphoma, though outcomes from lymphoma trials are not analyzed in the current study.
At a wholesale acquisition cost of $475,000 per infusion, it is the most expensive existing oncology therapy to date, and can be accompanied by expensive, potentially fatal adverse effects.
However, clinical trials suggest that tisagenlecleucel can offer years of relapse-free remission, thereby allowing patients to forgo other expensive therapies such as hematopoietic stem cell transplantation (HSCT).
“Although tisagenlecleucel-induced remission rates are promising, compared with those of established therapies (greater than 80% vs. less than 50%), only short-term follow-up data currently exist,” the investigators wrote in the Journal of Clinical Oncology.
“Given the high cost and broad applicability in other malignancies of tisagenlecleucel, a pressing question for policy makers, payers, patients, and clinicians is whether the cost of therapy represents reasonable value.”
The study used a Markov model to assess various long-term clinical outcome rates and cost thresholds of tisagenlecleucel. The lifetime cost of therapy was assessed and compared with costs of existing therapies.
The results showed that a 5-year relapse free survival rate of 40% would make the present cost ($475,000) of tisagenlecleucel economically reasonable. In this scenario, the increased life expectancy would be 12.1 years and would result in an additional 5.07 quality-adjusted life years (QALY) gained at a cost of $61,000 per QALY, compared with blinatumomab.
But if long-term outcomes are less favorable, tisagenlecleucel becomes much less cost effective. A 5-year relapse-free survival rate of 20% would drop increased life expectancy to 3.8 years, resulting in 1.80 QALYs gained and raising the cost to $151,000 per QALY.
“Our results suggest that at tisagenlecleucel’s current price and payment structure, its economic value is uncertain,” the investigators wrote.
They suggested a price drop to $200,000 or $350,000, which would allow the drug to remain cost effective even in a worse-case scenario, in which patients relapse and tisagenlecleucel is a bridge to transplant.
Another option is to move to outcomes-based pricing. Making payment conditional on 7 months of remission would make the treatment cost effective, according to the analysis.
“Price reductions of tisagenlecleucel or payment only for longer-term remissions would favorably influence cost-effectiveness, even if long-term clinical outcomes are modest,” the investigators wrote.
The study was funded by a Veterans Affairs Office of Academic Affiliations advanced fellowship in health service and research development, and a National Center for Advancing Translational Science Clinical and Translational Science Award.
One of the study coauthors reported consulting and research funding from Novartis.
The cost-effectiveness of tisagenlecleucel (Kymriah) depends on long-term clinical outcomes, which are presently unknown, according to investigators.
If the long-term outcomes are more modest than clinical trials suggest, then payers may be unwilling to cover the costly therapy, reported John K. Lin, MD, of Stanford University, and his colleagues.
Lowering the price or setting up an outcomes-based pricing structure may be necessary to get insurers to cover the therapy.
Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the U.S. Food and Drug Administration in August 2017 for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL).
In 2018, the FDA expanded the indication for tisagenlecleucel to include adults with relapsed or refractory large B-cell lymphoma, though outcomes from lymphoma trials are not analyzed in the current study.
At a wholesale acquisition cost of $475,000 per infusion, it is the most expensive existing oncology therapy to date, and can be accompanied by expensive, potentially fatal adverse effects.
However, clinical trials suggest that tisagenlecleucel can offer years of relapse-free remission, thereby allowing patients to forgo other expensive therapies such as hematopoietic stem cell transplantation (HSCT).
“Although tisagenlecleucel-induced remission rates are promising, compared with those of established therapies (greater than 80% vs. less than 50%), only short-term follow-up data currently exist,” the investigators wrote in the Journal of Clinical Oncology.
“Given the high cost and broad applicability in other malignancies of tisagenlecleucel, a pressing question for policy makers, payers, patients, and clinicians is whether the cost of therapy represents reasonable value.”
The study used a Markov model to assess various long-term clinical outcome rates and cost thresholds of tisagenlecleucel. The lifetime cost of therapy was assessed and compared with costs of existing therapies.
The results showed that a 5-year relapse free survival rate of 40% would make the present cost ($475,000) of tisagenlecleucel economically reasonable. In this scenario, the increased life expectancy would be 12.1 years and would result in an additional 5.07 quality-adjusted life years (QALY) gained at a cost of $61,000 per QALY, compared with blinatumomab.
But if long-term outcomes are less favorable, tisagenlecleucel becomes much less cost effective. A 5-year relapse-free survival rate of 20% would drop increased life expectancy to 3.8 years, resulting in 1.80 QALYs gained and raising the cost to $151,000 per QALY.
“Our results suggest that at tisagenlecleucel’s current price and payment structure, its economic value is uncertain,” the investigators wrote.
They suggested a price drop to $200,000 or $350,000, which would allow the drug to remain cost effective even in a worse-case scenario, in which patients relapse and tisagenlecleucel is a bridge to transplant.
Another option is to move to outcomes-based pricing. Making payment conditional on 7 months of remission would make the treatment cost effective, according to the analysis.
“Price reductions of tisagenlecleucel or payment only for longer-term remissions would favorably influence cost-effectiveness, even if long-term clinical outcomes are modest,” the investigators wrote.
The study was funded by a Veterans Affairs Office of Academic Affiliations advanced fellowship in health service and research development, and a National Center for Advancing Translational Science Clinical and Translational Science Award.
One of the study coauthors reported consulting and research funding from Novartis.