Pharmacy

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has expanded the approved indication for blinatumomab (Blincyto®).

The drug is now approved to treat adults and children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission (CR) with minimal residual disease (MRD) greater than or equal to 0.1%.

Blinatumomab received accelerated approval for this indication because the drug has not yet shown a clinical benefit in these patients.

The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on surrogate or intermediate endpoints—in this case, MRD response rate and hematologic relapse-free survival (RFS)—that are reasonably likely to predict clinical benefit.

Continued approval of blinatumomab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

“This is the first FDA-approved treatment for patients with MRD-positive ALL,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

“Because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer. We look forward to furthering our understanding about the reduction in MRD after treatment with Blincyto. Studies are being conducted to assess how Blincyto affects long-term survival outcomes in patients with MRD.”

About blinatumomab

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, the FDA granted blinatumomab accelerated approval to treat adults with Philadelphia chromosome-negative (Ph-) relapsed/refractory BCP-ALL.

In 2016, the FDA granted the therapy accelerated approval for pediatric patients with Ph- relapsed/refractory BCP-ALL.

Last year, the FDA granted blinatumomab full approval for pediatric and adult patients with Ph- or Ph+ relapsed/refractory BCP-ALL.

The FDA-approved prescribing information for blinatumomab includes a boxed warning for cytokine release syndrome and neurologic toxicities. Blinatumomab is also under a risk evaluation and mitigation strategy program in the US.

BLAST study

The new accelerated approval for blinatumomab was supported by results from the phase 2 BLAST study, which were published in Blood in January.

The study enrolled adults with MRD-positive BCP-ALL in complete hematologic remission after 3 or more cycles of intensive chemotherapy.

Patients received continuous intravenous infusions of blinatumomab at 15 μg/m²/day for 4 weeks, followed by 2 weeks off. They received up to 4 cycles of treatment and could undergo hematopoietic stem cell transplant (HSCT) at any time after the first cycle.

In all, there were 116 patients who received at least 1 infusion of blinatumomab. Seventy-six patients went on to HSCT while in continuous CR after cycle 1 (n=27), 2 (n=36), or 3/4 (n=13).

The study’s primary endpoint was the rate of complete MRD response within the first treatment cycle, and 78% of evaluable patients (88/113) achieved this endpoint.

A key secondary endpoint was RFS at 18 months. There were 110 patients evaluable for this endpoint. They all had Ph- BCP-ALL and <5% blasts at baseline.

The estimated RFS at 18 months was 54%, and the median RFS was 18.9 months. The median RFS was 24.6 months for patients treated in first CR and 11.0 months for patients treated in a later CR (P=0.004).

Another key endpoint was overall survival (OS). The median OS was 36.5 months, both for the 110 patients in the RFS analysis and for the entire study population.

In a landmark analysis, complete MRD responders had longer OS than MRD nonresponders—38.9 months and 12.5 months, respectively (P=0.002). And complete MRD responders had longer RFS than nonresponders—23.6 months and 5.7 months, respectively (P=0.002).

All 116 patients who started cycle 1 had at least 1 adverse event (AE). The rate of grade 3 AEs was 33%, and the rate of grade 4 AEs was 27%. These AEs were considered treatment-related in 29% (grade 3) and 22% (grade 4) of patients.

Four (3%) patients developed cytokine release syndrome—2 with grade 1 and 2 with grade 3. All of these events occurred during cycle 1.

Fifty-three percent of patients (n=61) had neurologic events. In most cases (97%, n=59), these events resolved.

There were 2 fatal AEs during the treatment period, both in cycle 1. One of these events—atypical pneumonitis with H1N1 influenza—was considered treatment-related. The other event—subdural hemorrhage—was considered unrelated to treatment.

There were 4 fatal AEs reported after blinatumomab treatment. Two of these deaths—due to multifocal CNS lesions and graft-versus-host disease—occurred in HSCT recipients. The other 2 deaths—due to disease progression and multi-organ failure—occurred in nontransplanted patients after relapse.

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has expanded the approved indication for blinatumomab (Blincyto®).

The drug is now approved to treat adults and children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission (CR) with minimal residual disease (MRD) greater than or equal to 0.1%.

Blinatumomab received accelerated approval for this indication because the drug has not yet shown a clinical benefit in these patients.

The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on surrogate or intermediate endpoints—in this case, MRD response rate and hematologic relapse-free survival (RFS)—that are reasonably likely to predict clinical benefit.

Continued approval of blinatumomab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

“This is the first FDA-approved treatment for patients with MRD-positive ALL,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

“Because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer. We look forward to furthering our understanding about the reduction in MRD after treatment with Blincyto. Studies are being conducted to assess how Blincyto affects long-term survival outcomes in patients with MRD.”

About blinatumomab

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, the FDA granted blinatumomab accelerated approval to treat adults with Philadelphia chromosome-negative (Ph-) relapsed/refractory BCP-ALL.

In 2016, the FDA granted the therapy accelerated approval for pediatric patients with Ph- relapsed/refractory BCP-ALL.

Last year, the FDA granted blinatumomab full approval for pediatric and adult patients with Ph- or Ph+ relapsed/refractory BCP-ALL.

The FDA-approved prescribing information for blinatumomab includes a boxed warning for cytokine release syndrome and neurologic toxicities. Blinatumomab is also under a risk evaluation and mitigation strategy program in the US.

BLAST study

The new accelerated approval for blinatumomab was supported by results from the phase 2 BLAST study, which were published in Blood in January.

The study enrolled adults with MRD-positive BCP-ALL in complete hematologic remission after 3 or more cycles of intensive chemotherapy.

Patients received continuous intravenous infusions of blinatumomab at 15 μg/m²/day for 4 weeks, followed by 2 weeks off. They received up to 4 cycles of treatment and could undergo hematopoietic stem cell transplant (HSCT) at any time after the first cycle.

In all, there were 116 patients who received at least 1 infusion of blinatumomab. Seventy-six patients went on to HSCT while in continuous CR after cycle 1 (n=27), 2 (n=36), or 3/4 (n=13).

The study’s primary endpoint was the rate of complete MRD response within the first treatment cycle, and 78% of evaluable patients (88/113) achieved this endpoint.

A key secondary endpoint was RFS at 18 months. There were 110 patients evaluable for this endpoint. They all had Ph- BCP-ALL and <5% blasts at baseline.

The estimated RFS at 18 months was 54%, and the median RFS was 18.9 months. The median RFS was 24.6 months for patients treated in first CR and 11.0 months for patients treated in a later CR (P=0.004).

Another key endpoint was overall survival (OS). The median OS was 36.5 months, both for the 110 patients in the RFS analysis and for the entire study population.

In a landmark analysis, complete MRD responders had longer OS than MRD nonresponders—38.9 months and 12.5 months, respectively (P=0.002). And complete MRD responders had longer RFS than nonresponders—23.6 months and 5.7 months, respectively (P=0.002).

All 116 patients who started cycle 1 had at least 1 adverse event (AE). The rate of grade 3 AEs was 33%, and the rate of grade 4 AEs was 27%. These AEs were considered treatment-related in 29% (grade 3) and 22% (grade 4) of patients.

Four (3%) patients developed cytokine release syndrome—2 with grade 1 and 2 with grade 3. All of these events occurred during cycle 1.

Fifty-three percent of patients (n=61) had neurologic events. In most cases (97%, n=59), these events resolved.

There were 2 fatal AEs during the treatment period, both in cycle 1. One of these events—atypical pneumonitis with H1N1 influenza—was considered treatment-related. The other event—subdural hemorrhage—was considered unrelated to treatment.

There were 4 fatal AEs reported after blinatumomab treatment. Two of these deaths—due to multifocal CNS lesions and graft-versus-host disease—occurred in HSCT recipients. The other 2 deaths—due to disease progression and multi-organ failure—occurred in nontransplanted patients after relapse.

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has expanded the approved indication for blinatumomab (Blincyto®).

The drug is now approved to treat adults and children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission (CR) with minimal residual disease (MRD) greater than or equal to 0.1%.

Blinatumomab received accelerated approval for this indication because the drug has not yet shown a clinical benefit in these patients.

The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on surrogate or intermediate endpoints—in this case, MRD response rate and hematologic relapse-free survival (RFS)—that are reasonably likely to predict clinical benefit.

Continued approval of blinatumomab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

“This is the first FDA-approved treatment for patients with MRD-positive ALL,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

“Because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer. We look forward to furthering our understanding about the reduction in MRD after treatment with Blincyto. Studies are being conducted to assess how Blincyto affects long-term survival outcomes in patients with MRD.”

About blinatumomab

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, the FDA granted blinatumomab accelerated approval to treat adults with Philadelphia chromosome-negative (Ph-) relapsed/refractory BCP-ALL.

In 2016, the FDA granted the therapy accelerated approval for pediatric patients with Ph- relapsed/refractory BCP-ALL.

Last year, the FDA granted blinatumomab full approval for pediatric and adult patients with Ph- or Ph+ relapsed/refractory BCP-ALL.

The FDA-approved prescribing information for blinatumomab includes a boxed warning for cytokine release syndrome and neurologic toxicities. Blinatumomab is also under a risk evaluation and mitigation strategy program in the US.

BLAST study

The new accelerated approval for blinatumomab was supported by results from the phase 2 BLAST study, which were published in Blood in January.

The study enrolled adults with MRD-positive BCP-ALL in complete hematologic remission after 3 or more cycles of intensive chemotherapy.

Patients received continuous intravenous infusions of blinatumomab at 15 μg/m²/day for 4 weeks, followed by 2 weeks off. They received up to 4 cycles of treatment and could undergo hematopoietic stem cell transplant (HSCT) at any time after the first cycle.

In all, there were 116 patients who received at least 1 infusion of blinatumomab. Seventy-six patients went on to HSCT while in continuous CR after cycle 1 (n=27), 2 (n=36), or 3/4 (n=13).

The study’s primary endpoint was the rate of complete MRD response within the first treatment cycle, and 78% of evaluable patients (88/113) achieved this endpoint.

A key secondary endpoint was RFS at 18 months. There were 110 patients evaluable for this endpoint. They all had Ph- BCP-ALL and <5% blasts at baseline.

The estimated RFS at 18 months was 54%, and the median RFS was 18.9 months. The median RFS was 24.6 months for patients treated in first CR and 11.0 months for patients treated in a later CR (P=0.004).

Another key endpoint was overall survival (OS). The median OS was 36.5 months, both for the 110 patients in the RFS analysis and for the entire study population.

In a landmark analysis, complete MRD responders had longer OS than MRD nonresponders—38.9 months and 12.5 months, respectively (P=0.002). And complete MRD responders had longer RFS than nonresponders—23.6 months and 5.7 months, respectively (P=0.002).

All 116 patients who started cycle 1 had at least 1 adverse event (AE). The rate of grade 3 AEs was 33%, and the rate of grade 4 AEs was 27%. These AEs were considered treatment-related in 29% (grade 3) and 22% (grade 4) of patients.

Four (3%) patients developed cytokine release syndrome—2 with grade 1 and 2 with grade 3. All of these events occurred during cycle 1.

Fifty-three percent of patients (n=61) had neurologic events. In most cases (97%, n=59), these events resolved.

There were 2 fatal AEs during the treatment period, both in cycle 1. One of these events—atypical pneumonitis with H1N1 influenza—was considered treatment-related. The other event—subdural hemorrhage—was considered unrelated to treatment.

There were 4 fatal AEs reported after blinatumomab treatment. Two of these deaths—due to multifocal CNS lesions and graft-versus-host disease—occurred in HSCT recipients. The other 2 deaths—due to disease progression and multi-organ failure—occurred in nontransplanted patients after relapse.

Henrique Orlandi Mourao

The US Food and Drug Administration (FDA) has granted orphan designation to MAX-40279 for the treatment of acute myeloid leukemia (AML).

MAX-40279 is a multi-target kinase inhibitor being developed by MaxiNovel Pharmaceuticals, Inc.

The drug mainly targets FMS-related tyrosine kinase 3 (FLT3) and fibroblast growth factor receptor (FGFR).

MAX-40279 demonstrated “potent” inhibition of FLT3 and FGFR in preclinical testing, according to MaxiNovel Pharmaceuticals, Inc.

The company is currently testing MAX-40279 in a phase 1 trial of patients with AML (NCT03412292).

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.

Henrique Orlandi Mourao

The US Food and Drug Administration (FDA) has granted orphan designation to MAX-40279 for the treatment of acute myeloid leukemia (AML).

MAX-40279 is a multi-target kinase inhibitor being developed by MaxiNovel Pharmaceuticals, Inc.

The drug mainly targets FMS-related tyrosine kinase 3 (FLT3) and fibroblast growth factor receptor (FGFR).

MAX-40279 demonstrated “potent” inhibition of FLT3 and FGFR in preclinical testing, according to MaxiNovel Pharmaceuticals, Inc.

The company is currently testing MAX-40279 in a phase 1 trial of patients with AML (NCT03412292).

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.

Henrique Orlandi Mourao

The US Food and Drug Administration (FDA) has granted orphan designation to MAX-40279 for the treatment of acute myeloid leukemia (AML).

MAX-40279 is a multi-target kinase inhibitor being developed by MaxiNovel Pharmaceuticals, Inc.

The drug mainly targets FMS-related tyrosine kinase 3 (FLT3) and fibroblast growth factor receptor (FGFR).

MAX-40279 demonstrated “potent” inhibition of FLT3 and FGFR in preclinical testing, according to MaxiNovel Pharmaceuticals, Inc.

The company is currently testing MAX-40279 in a phase 1 trial of patients with AML (NCT03412292).

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 from Business Wire

Two hemophilia organizations have notified the public of 5 deaths in adult patients receiving emicizumab (Hemlibra).

All 5 deaths—occurring in 2016 (n=1), 2017 (n=2), and this year (n=2)—were deemed unrelated to emicizumab by the investigator or treating physician.

The National Hemophilia Foundation and Hemophilia Federation of America reported these deaths after receiving notifications from Genentech.

The company said it has limited information about the circumstances of the deaths.

However, Genentech did say the 2016 death, 1 of the 2017 deaths, and 1 of the 2018 deaths occurred in patients receiving emicizumab via a compassionate use program.

Compassionate use of emicizumab has been available on a case-by-case basis, following a request to Roche from a patient’s treating physician, if the patient has a serious or life-threatening condition, has exhausted all other treatment options, and is unable to participate in a clinical trial.

The other death in 2017 occurred in a patient on the phase 3 HAVEN 1 trial and was reported along with the other results from that trial.

The remaining death in 2018 was in a patient receiving emicizumab via an expanded access protocol.

This protocol, which was reviewed by the US Food and Drug Administration, allowed US patients who were not participating in a clinical trial of emicizumab but who met eligibility criteria similar to key studies to have access to emicizumab prior to approval, which occurred in November 2017.

In response to the deaths, Genentech has pledged to share information on any adverse events that impact the overall benefit/risk profile of emicizumab.

“We are committed to providing timely and transparent updates on the safety profile of Hemlibra to health authorities, healthcare professionals, and the hemophilia community,” the company said.

For more information, patients and healthcare providers can call Genentech’s medical communications line at 1-800-821-8590. 

Photo from Business Wire

Two hemophilia organizations have notified the public of 5 deaths in adult patients receiving emicizumab (Hemlibra).

All 5 deaths—occurring in 2016 (n=1), 2017 (n=2), and this year (n=2)—were deemed unrelated to emicizumab by the investigator or treating physician.

The National Hemophilia Foundation and Hemophilia Federation of America reported these deaths after receiving notifications from Genentech.

The company said it has limited information about the circumstances of the deaths.

However, Genentech did say the 2016 death, 1 of the 2017 deaths, and 1 of the 2018 deaths occurred in patients receiving emicizumab via a compassionate use program.

Compassionate use of emicizumab has been available on a case-by-case basis, following a request to Roche from a patient’s treating physician, if the patient has a serious or life-threatening condition, has exhausted all other treatment options, and is unable to participate in a clinical trial.

The other death in 2017 occurred in a patient on the phase 3 HAVEN 1 trial and was reported along with the other results from that trial.

The remaining death in 2018 was in a patient receiving emicizumab via an expanded access protocol.

This protocol, which was reviewed by the US Food and Drug Administration, allowed US patients who were not participating in a clinical trial of emicizumab but who met eligibility criteria similar to key studies to have access to emicizumab prior to approval, which occurred in November 2017.

In response to the deaths, Genentech has pledged to share information on any adverse events that impact the overall benefit/risk profile of emicizumab.

“We are committed to providing timely and transparent updates on the safety profile of Hemlibra to health authorities, healthcare professionals, and the hemophilia community,” the company said.

For more information, patients and healthcare providers can call Genentech’s medical communications line at 1-800-821-8590. 

Photo from Business Wire

Two hemophilia organizations have notified the public of 5 deaths in adult patients receiving emicizumab (Hemlibra).

All 5 deaths—occurring in 2016 (n=1), 2017 (n=2), and this year (n=2)—were deemed unrelated to emicizumab by the investigator or treating physician.

The National Hemophilia Foundation and Hemophilia Federation of America reported these deaths after receiving notifications from Genentech.

The company said it has limited information about the circumstances of the deaths.

However, Genentech did say the 2016 death, 1 of the 2017 deaths, and 1 of the 2018 deaths occurred in patients receiving emicizumab via a compassionate use program.

Compassionate use of emicizumab has been available on a case-by-case basis, following a request to Roche from a patient’s treating physician, if the patient has a serious or life-threatening condition, has exhausted all other treatment options, and is unable to participate in a clinical trial.

The other death in 2017 occurred in a patient on the phase 3 HAVEN 1 trial and was reported along with the other results from that trial.

The remaining death in 2018 was in a patient receiving emicizumab via an expanded access protocol.

This protocol, which was reviewed by the US Food and Drug Administration, allowed US patients who were not participating in a clinical trial of emicizumab but who met eligibility criteria similar to key studies to have access to emicizumab prior to approval, which occurred in November 2017.

In response to the deaths, Genentech has pledged to share information on any adverse events that impact the overall benefit/risk profile of emicizumab.

“We are committed to providing timely and transparent updates on the safety profile of Hemlibra to health authorities, healthcare professionals, and the hemophilia community,” the company said.

For more information, patients and healthcare providers can call Genentech’s medical communications line at 1-800-821-8590. 

Photo courtesy of the CDC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization to a generic version of prasugrel called Prasugrel Mylan.

Mylan S.A.S. is seeking approval for this product to be co-administered with acetylsalicylic acid for the prevention of atherothrombotic events in adults with acute coronary syndrome (ie, unstable angina, non-ST segment elevation myocardial infarction, or ST segment elevation myocardial infarction) undergoing primary or delayed percutaneous coronary intervention.

The CHMP’s opinion on Prasugrel Mylan will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, Prasugrel Mylan will be available as 5 mg and 10 mg film-coated tablets.

Prasugrel is an inhibitor of platelet activation and aggregation that acts through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function can reduce the risk of cardiovascular events such as death, myocardial infarction, or stroke.

Prasugrel Mylan is a generic of Efient, which has been authorized in the European Union since 2009.

According to the CHMP, studies have demonstrated that Prasugrel Mylan is of “satisfactory quality” and bioequivalent to Efient.

In the TRITON–TIMI 38 study, treatment with prasugrel (Efient) was associated with significantly reduced rates of ischemic events, including stent thrombosis, when compared to treatment with clopidogrel in patients with moderate- to high-risk acute coronary syndromes with scheduled percutaneous coronary intervention.

However, prasugrel was also associated with an increased risk of major bleeding, including fatal bleeding. Still, there was no significant difference in mortality between the treatment groups.

These results were published in NEJM in 2007.

Photo courtesy of the CDC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization to a generic version of prasugrel called Prasugrel Mylan.

Mylan S.A.S. is seeking approval for this product to be co-administered with acetylsalicylic acid for the prevention of atherothrombotic events in adults with acute coronary syndrome (ie, unstable angina, non-ST segment elevation myocardial infarction, or ST segment elevation myocardial infarction) undergoing primary or delayed percutaneous coronary intervention.

The CHMP’s opinion on Prasugrel Mylan will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, Prasugrel Mylan will be available as 5 mg and 10 mg film-coated tablets.

Prasugrel is an inhibitor of platelet activation and aggregation that acts through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function can reduce the risk of cardiovascular events such as death, myocardial infarction, or stroke.

Prasugrel Mylan is a generic of Efient, which has been authorized in the European Union since 2009.

According to the CHMP, studies have demonstrated that Prasugrel Mylan is of “satisfactory quality” and bioequivalent to Efient.

In the TRITON–TIMI 38 study, treatment with prasugrel (Efient) was associated with significantly reduced rates of ischemic events, including stent thrombosis, when compared to treatment with clopidogrel in patients with moderate- to high-risk acute coronary syndromes with scheduled percutaneous coronary intervention.

However, prasugrel was also associated with an increased risk of major bleeding, including fatal bleeding. Still, there was no significant difference in mortality between the treatment groups.

These results were published in NEJM in 2007.

Photo courtesy of the CDC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization to a generic version of prasugrel called Prasugrel Mylan.

Mylan S.A.S. is seeking approval for this product to be co-administered with acetylsalicylic acid for the prevention of atherothrombotic events in adults with acute coronary syndrome (ie, unstable angina, non-ST segment elevation myocardial infarction, or ST segment elevation myocardial infarction) undergoing primary or delayed percutaneous coronary intervention.

The CHMP’s opinion on Prasugrel Mylan will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, Prasugrel Mylan will be available as 5 mg and 10 mg film-coated tablets.

Prasugrel is an inhibitor of platelet activation and aggregation that acts through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function can reduce the risk of cardiovascular events such as death, myocardial infarction, or stroke.

Prasugrel Mylan is a generic of Efient, which has been authorized in the European Union since 2009.

According to the CHMP, studies have demonstrated that Prasugrel Mylan is of “satisfactory quality” and bioequivalent to Efient.

In the TRITON–TIMI 38 study, treatment with prasugrel (Efient) was associated with significantly reduced rates of ischemic events, including stent thrombosis, when compared to treatment with clopidogrel in patients with moderate- to high-risk acute coronary syndromes with scheduled percutaneous coronary intervention.

However, prasugrel was also associated with an increased risk of major bleeding, including fatal bleeding. Still, there was no significant difference in mortality between the treatment groups.

These results were published in NEJM in 2007.

Photo from Business Wire

Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved the bispecific factor IXa- and factor X-directed antibody emicizumab (Hemlibra), according to Chugai Pharmaceutical Co., Ltd.

Emicizumab is now approved for use in Japan as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A and factor VIII inhibitors.

There are a few conditions for this approval, including requirements for a risk management plan, early phase post-marketing vigilance, and post-marketing drug use surveillance.

A risk management plan is intended to assess measures for appropriate management of the risks associated with a drug, either at regular intervals or in response to the progress of post-marketing surveillance.

According to Japan’s Pharmaceuticals and Medical Devices Agency, a risk management plan must consist of 3 elements:

1. Safety specification—Important adverse drug reactions and missing information
2. Pharmacovigilance activities—Information collection activities performed in the post-marketing period
3. Risk-minimization activities—Safety measures taken to minimize risks, which consists of providing information to healthcare professionals and setting the terms of use for a drug.

For the early phase post-marketing vigilance requirement, Chugai must provide safety information to healthcare professionals and collect information on adverse reactions to emicizumab in the early post-marketing phase.

Post-marketing drug use surveillance for emicizumab will include all patients receiving the product and is scheduled to continue until data is collected from approximately 100 people. The goal is to understand background information on patients receiving emicizumab, as well as to collect safety and efficacy data on the product and take necessary measures for the appropriate use of emicizumab.

The data collected via this surveillance effort will be reviewed to determine whether new surveillance or further safety measures are needed. Results of the surveillance will be reported to the regulatory authorities, and the data will be presented at scientific meetings, according to Chugai.

Phase 3 studies

The MHLW’s approval of emicizumab is based on data from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.

Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July 2017. Updated results from HAVEN 2 were presented at the 2017 ASH Annual Meeting in December.

HAVEN 1

This study enrolled 109 patients (age 12 and older) with hemophilia A and factor VIII inhibitors who were previously treated with bypassing agents (BPAs) on-demand or as prophylaxis.

The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.

There was a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).

Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.

Two patients experienced thromboembolic events (TEs). Three had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.

Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.

HAVEN 2

In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with factor VIII inhibitors.

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.

Forty patients had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).

There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.

Photo from Business Wire

Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved the bispecific factor IXa- and factor X-directed antibody emicizumab (Hemlibra), according to Chugai Pharmaceutical Co., Ltd.

Emicizumab is now approved for use in Japan as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A and factor VIII inhibitors.

There are a few conditions for this approval, including requirements for a risk management plan, early phase post-marketing vigilance, and post-marketing drug use surveillance.

A risk management plan is intended to assess measures for appropriate management of the risks associated with a drug, either at regular intervals or in response to the progress of post-marketing surveillance.

According to Japan’s Pharmaceuticals and Medical Devices Agency, a risk management plan must consist of 3 elements:

1. Safety specification—Important adverse drug reactions and missing information
2. Pharmacovigilance activities—Information collection activities performed in the post-marketing period
3. Risk-minimization activities—Safety measures taken to minimize risks, which consists of providing information to healthcare professionals and setting the terms of use for a drug.

For the early phase post-marketing vigilance requirement, Chugai must provide safety information to healthcare professionals and collect information on adverse reactions to emicizumab in the early post-marketing phase.

Post-marketing drug use surveillance for emicizumab will include all patients receiving the product and is scheduled to continue until data is collected from approximately 100 people. The goal is to understand background information on patients receiving emicizumab, as well as to collect safety and efficacy data on the product and take necessary measures for the appropriate use of emicizumab.

The data collected via this surveillance effort will be reviewed to determine whether new surveillance or further safety measures are needed. Results of the surveillance will be reported to the regulatory authorities, and the data will be presented at scientific meetings, according to Chugai.

Phase 3 studies

The MHLW’s approval of emicizumab is based on data from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.

Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July 2017. Updated results from HAVEN 2 were presented at the 2017 ASH Annual Meeting in December.

HAVEN 1

This study enrolled 109 patients (age 12 and older) with hemophilia A and factor VIII inhibitors who were previously treated with bypassing agents (BPAs) on-demand or as prophylaxis.

The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.

There was a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).

Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.

Two patients experienced thromboembolic events (TEs). Three had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.

Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.

HAVEN 2

In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with factor VIII inhibitors.

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.

Forty patients had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).

There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.

Photo from Business Wire

Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved the bispecific factor IXa- and factor X-directed antibody emicizumab (Hemlibra), according to Chugai Pharmaceutical Co., Ltd.

Emicizumab is now approved for use in Japan as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A and factor VIII inhibitors.

There are a few conditions for this approval, including requirements for a risk management plan, early phase post-marketing vigilance, and post-marketing drug use surveillance.

A risk management plan is intended to assess measures for appropriate management of the risks associated with a drug, either at regular intervals or in response to the progress of post-marketing surveillance.

According to Japan’s Pharmaceuticals and Medical Devices Agency, a risk management plan must consist of 3 elements:

1. Safety specification—Important adverse drug reactions and missing information
2. Pharmacovigilance activities—Information collection activities performed in the post-marketing period
3. Risk-minimization activities—Safety measures taken to minimize risks, which consists of providing information to healthcare professionals and setting the terms of use for a drug.

For the early phase post-marketing vigilance requirement, Chugai must provide safety information to healthcare professionals and collect information on adverse reactions to emicizumab in the early post-marketing phase.

Post-marketing drug use surveillance for emicizumab will include all patients receiving the product and is scheduled to continue until data is collected from approximately 100 people. The goal is to understand background information on patients receiving emicizumab, as well as to collect safety and efficacy data on the product and take necessary measures for the appropriate use of emicizumab.

The data collected via this surveillance effort will be reviewed to determine whether new surveillance or further safety measures are needed. Results of the surveillance will be reported to the regulatory authorities, and the data will be presented at scientific meetings, according to Chugai.

Phase 3 studies

The MHLW’s approval of emicizumab is based on data from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.

Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July 2017. Updated results from HAVEN 2 were presented at the 2017 ASH Annual Meeting in December.

HAVEN 1

This study enrolled 109 patients (age 12 and older) with hemophilia A and factor VIII inhibitors who were previously treated with bypassing agents (BPAs) on-demand or as prophylaxis.

The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.

There was a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).

Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.

Two patients experienced thromboembolic events (TEs). Three had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.

Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.

HAVEN 2

In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with factor VIII inhibitors.

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.

Forty patients had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).

There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.

Photo from Novartis

The US Food and Drug Administration (FDA) has expanded the approved indication for nilotinib (Tasigna®) to include the treatment of children.

The drug is now approved to treat patients age 1 and older who have newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase.

Nilotinib is also approved to treat pediatric patients age 1 and older who have chronic phase, Ph+ CML that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, as well as adults with Ph+ CML in chronic phase and accelerated phase that is resistant or intolerant to prior therapy including imatinib.

The new pediatric indications for nilotinib, granted under the FDA’s priority review designation, are based on results from 2 studies of the drug—a phase 1 and phase 2.

According to Novartis, the studies included 69 CML patients who ranged in age from 2 to 17. They had either newly diagnosed, chronic phase, Ph+ CML or chronic phase, Ph+ CML with resistance or intolerance to prior TKI therapy.

In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% at 12 cycles, with 15 patients achieving MMR.

In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% at 12 cycles, with 18 patients being in MMR.

In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.

Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.

The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.

There were no deaths on treatment or after treatment discontinuation.

There was 1 patient with resistant/intolerant CML who progressed to advance phase/blast crisis after about 10 months on nilotinib.

Photo from Novartis

The US Food and Drug Administration (FDA) has expanded the approved indication for nilotinib (Tasigna®) to include the treatment of children.

The drug is now approved to treat patients age 1 and older who have newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase.

Nilotinib is also approved to treat pediatric patients age 1 and older who have chronic phase, Ph+ CML that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, as well as adults with Ph+ CML in chronic phase and accelerated phase that is resistant or intolerant to prior therapy including imatinib.

The new pediatric indications for nilotinib, granted under the FDA’s priority review designation, are based on results from 2 studies of the drug—a phase 1 and phase 2.

According to Novartis, the studies included 69 CML patients who ranged in age from 2 to 17. They had either newly diagnosed, chronic phase, Ph+ CML or chronic phase, Ph+ CML with resistance or intolerance to prior TKI therapy.

In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% at 12 cycles, with 15 patients achieving MMR.

In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% at 12 cycles, with 18 patients being in MMR.

In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.

Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.

The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.

There were no deaths on treatment or after treatment discontinuation.

There was 1 patient with resistant/intolerant CML who progressed to advance phase/blast crisis after about 10 months on nilotinib.

Photo from Novartis

The US Food and Drug Administration (FDA) has expanded the approved indication for nilotinib (Tasigna®) to include the treatment of children.

The drug is now approved to treat patients age 1 and older who have newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase.

Nilotinib is also approved to treat pediatric patients age 1 and older who have chronic phase, Ph+ CML that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, as well as adults with Ph+ CML in chronic phase and accelerated phase that is resistant or intolerant to prior therapy including imatinib.

The new pediatric indications for nilotinib, granted under the FDA’s priority review designation, are based on results from 2 studies of the drug—a phase 1 and phase 2.

According to Novartis, the studies included 69 CML patients who ranged in age from 2 to 17. They had either newly diagnosed, chronic phase, Ph+ CML or chronic phase, Ph+ CML with resistance or intolerance to prior TKI therapy.

In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% at 12 cycles, with 15 patients achieving MMR.

In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% at 12 cycles, with 18 patients being in MMR.

In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.

Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.

The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.

There were no deaths on treatment or after treatment discontinuation.

There was 1 patient with resistant/intolerant CML who progressed to advance phase/blast crisis after about 10 months on nilotinib.

Syringe

Health Canada has approved a subcutaneous (SC) formulation of rituximab (Rituxan®) to treat patients with chronic lymphocytic leukemia (CLL).

The product is now approved for use in combination with fludarabine and cyclophosphamide to treat patients with previously treated or untreated CLL, Binet Stage B or C.

The SC formulation is intended to provide a more convenient delivery method than intravenous (IV) rituximab. The SC formulation enables administration of the drug in large volumes under the skin.

“The approval of Rituxan SC is exciting news and a meaningful advancement for those living with CLL, as intravenous treatments can take around 4 hours to receive, requiring patients to spend up to a half day sitting in the chemo suite,” said Robin Markowitz, chief executive officer of Lymphoma Canada.

“The administration of Rituxan SC only takes 7 minutes, giving patients valuable time back in their day.”

SAWYER study

Health Canada’s approval of SC rituximab is based on data from the phase 1b SAWYER study. This randomized study was conducted in patients with previously untreated CLL to investigate the pharmacokinetic profile, safety, and efficacy of SC rituximab in combination with chemotherapy.

Results from this study were published in The Lancet Haematology in March 2016.

The trial included 176 patients who were randomized to receive SC rituximab (1600 mg, n=88) or IV rituximab (500 mg/m², n=88) on day 1 from cycles 2 to 6. In cycle 1, both groups received IV rituximab (375 mg/m²) on day 0.

All patients also received fludarabine (IV 25 mg/m² on days 1-3 of all cycles or orally at either 25 mg/m² on days 1-5 of all cycles or 30-40 mg/m² on days 1-3 of all cycles) and cyclophosphamide (IV at 250 mg/m² on days 1-3 of all cycles or orally at either 150 mg/m² on days 1-5 of all cycles or 200-250 mg/m² on days 1-3 of all cycles) every 4 weeks for up to 6 cycles.

The primary endpoint was pharmacokinetic noninferiority of SC to IV rituximab assessed at cycle 5. At that time, the geometric mean trough serum concentration in the SC rituximab arm was noninferior to that in the IV arm—97.5 µg/mL and 61.5 µg/mL, respectively—with an adjusted geometric mean ratio of 1.53 (90% CI, 1.27 to 1.85).

Safety was a secondary endpoint, and efficacy was an exploratory endpoint.

The overall response rate was 85% in the SC arm and 81% in the IV arm. Complete response rates were 26% and 33%, respectively.

Rates of adverse events (AEs) were 96% in the SC arm and 91% in the IV arm. Rates of grade 3 or higher AEs were 69% and 71%, respectively, and rates of serious AEs were 29% and 33%, respectively.

The most common serious AE overall was febrile neutropenia, which occurred in 11% of patients in the SC arm and 4% in the IV arm.

The most common AEs of any grade (occurring in >20% of patients in either arm) were:

• Neutropenia—65% with SC and 58% with IV
• Thrombocytopenia—24% with SC and 26% with IV
• Anemia—13% with SC and 24% with IV
• Nausea—38% with SC and 35% with IV
• Vomiting—21% with SC and 22% with IV
• Pyrexia—32% with SC and 25% with IV
• Injection-site erythema—26% with SC and 0% with IV.

Local cutaneous reactions were reported in 42% of patients in the SC arm. The most common of these were injection-site erythema (26%) and injection-site pain (16%).

Syringe

Health Canada has approved a subcutaneous (SC) formulation of rituximab (Rituxan®) to treat patients with chronic lymphocytic leukemia (CLL).

The product is now approved for use in combination with fludarabine and cyclophosphamide to treat patients with previously treated or untreated CLL, Binet Stage B or C.

The SC formulation is intended to provide a more convenient delivery method than intravenous (IV) rituximab. The SC formulation enables administration of the drug in large volumes under the skin.

“The approval of Rituxan SC is exciting news and a meaningful advancement for those living with CLL, as intravenous treatments can take around 4 hours to receive, requiring patients to spend up to a half day sitting in the chemo suite,” said Robin Markowitz, chief executive officer of Lymphoma Canada.

“The administration of Rituxan SC only takes 7 minutes, giving patients valuable time back in their day.”

SAWYER study

Health Canada’s approval of SC rituximab is based on data from the phase 1b SAWYER study. This randomized study was conducted in patients with previously untreated CLL to investigate the pharmacokinetic profile, safety, and efficacy of SC rituximab in combination with chemotherapy.

Results from this study were published in The Lancet Haematology in March 2016.

The trial included 176 patients who were randomized to receive SC rituximab (1600 mg, n=88) or IV rituximab (500 mg/m², n=88) on day 1 from cycles 2 to 6. In cycle 1, both groups received IV rituximab (375 mg/m²) on day 0.

All patients also received fludarabine (IV 25 mg/m² on days 1-3 of all cycles or orally at either 25 mg/m² on days 1-5 of all cycles or 30-40 mg/m² on days 1-3 of all cycles) and cyclophosphamide (IV at 250 mg/m² on days 1-3 of all cycles or orally at either 150 mg/m² on days 1-5 of all cycles or 200-250 mg/m² on days 1-3 of all cycles) every 4 weeks for up to 6 cycles.

The primary endpoint was pharmacokinetic noninferiority of SC to IV rituximab assessed at cycle 5. At that time, the geometric mean trough serum concentration in the SC rituximab arm was noninferior to that in the IV arm—97.5 µg/mL and 61.5 µg/mL, respectively—with an adjusted geometric mean ratio of 1.53 (90% CI, 1.27 to 1.85).

Safety was a secondary endpoint, and efficacy was an exploratory endpoint.

The overall response rate was 85% in the SC arm and 81% in the IV arm. Complete response rates were 26% and 33%, respectively.

Rates of adverse events (AEs) were 96% in the SC arm and 91% in the IV arm. Rates of grade 3 or higher AEs were 69% and 71%, respectively, and rates of serious AEs were 29% and 33%, respectively.

The most common serious AE overall was febrile neutropenia, which occurred in 11% of patients in the SC arm and 4% in the IV arm.

The most common AEs of any grade (occurring in >20% of patients in either arm) were:

• Neutropenia—65% with SC and 58% with IV
• Thrombocytopenia—24% with SC and 26% with IV
• Anemia—13% with SC and 24% with IV
• Nausea—38% with SC and 35% with IV
• Vomiting—21% with SC and 22% with IV
• Pyrexia—32% with SC and 25% with IV
• Injection-site erythema—26% with SC and 0% with IV.

Local cutaneous reactions were reported in 42% of patients in the SC arm. The most common of these were injection-site erythema (26%) and injection-site pain (16%).

Syringe

Health Canada has approved a subcutaneous (SC) formulation of rituximab (Rituxan®) to treat patients with chronic lymphocytic leukemia (CLL).

The product is now approved for use in combination with fludarabine and cyclophosphamide to treat patients with previously treated or untreated CLL, Binet Stage B or C.

The SC formulation is intended to provide a more convenient delivery method than intravenous (IV) rituximab. The SC formulation enables administration of the drug in large volumes under the skin.

“The approval of Rituxan SC is exciting news and a meaningful advancement for those living with CLL, as intravenous treatments can take around 4 hours to receive, requiring patients to spend up to a half day sitting in the chemo suite,” said Robin Markowitz, chief executive officer of Lymphoma Canada.

“The administration of Rituxan SC only takes 7 minutes, giving patients valuable time back in their day.”

SAWYER study

Health Canada’s approval of SC rituximab is based on data from the phase 1b SAWYER study. This randomized study was conducted in patients with previously untreated CLL to investigate the pharmacokinetic profile, safety, and efficacy of SC rituximab in combination with chemotherapy.

Results from this study were published in The Lancet Haematology in March 2016.

The trial included 176 patients who were randomized to receive SC rituximab (1600 mg, n=88) or IV rituximab (500 mg/m², n=88) on day 1 from cycles 2 to 6. In cycle 1, both groups received IV rituximab (375 mg/m²) on day 0.

All patients also received fludarabine (IV 25 mg/m² on days 1-3 of all cycles or orally at either 25 mg/m² on days 1-5 of all cycles or 30-40 mg/m² on days 1-3 of all cycles) and cyclophosphamide (IV at 250 mg/m² on days 1-3 of all cycles or orally at either 150 mg/m² on days 1-5 of all cycles or 200-250 mg/m² on days 1-3 of all cycles) every 4 weeks for up to 6 cycles.

The primary endpoint was pharmacokinetic noninferiority of SC to IV rituximab assessed at cycle 5. At that time, the geometric mean trough serum concentration in the SC rituximab arm was noninferior to that in the IV arm—97.5 µg/mL and 61.5 µg/mL, respectively—with an adjusted geometric mean ratio of 1.53 (90% CI, 1.27 to 1.85).

Safety was a secondary endpoint, and efficacy was an exploratory endpoint.

The overall response rate was 85% in the SC arm and 81% in the IV arm. Complete response rates were 26% and 33%, respectively.

Rates of adverse events (AEs) were 96% in the SC arm and 91% in the IV arm. Rates of grade 3 or higher AEs were 69% and 71%, respectively, and rates of serious AEs were 29% and 33%, respectively.

The most common serious AE overall was febrile neutropenia, which occurred in 11% of patients in the SC arm and 4% in the IV arm.

The most common AEs of any grade (occurring in >20% of patients in either arm) were:

• Neutropenia—65% with SC and 58% with IV
• Thrombocytopenia—24% with SC and 26% with IV
• Anemia—13% with SC and 24% with IV
• Nausea—38% with SC and 35% with IV
• Vomiting—21% with SC and 22% with IV
• Pyrexia—32% with SC and 25% with IV
• Injection-site erythema—26% with SC and 0% with IV.

Local cutaneous reactions were reported in 42% of patients in the SC arm. The most common of these were injection-site erythema (26%) and injection-site pain (16%).

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved brentuximab vedotin (ADCETRIS) in combination with chemotherapy for adults with previously untreated, stage III or IV classical Hodgkin lymphoma (cHL).

This is the fifth approved indication for BV in the US and the first regimen approved for frontline, stage III/IV cHL in the US in more than 40 years.

“The standard of care for treating newly diagnosed, advanced Hodgkin lymphoma has not changed in more than 4 decades,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective—to no avail.”

The ECHELON-1 study changed that, according to Dr Connors.

“The ECHELON-1 study results demonstrated superior efficacy of the ADCETRIS plus chemotherapy regimen, when compared to the standard of care, while removing bleomycin—an agent that can cause unpredictable and sometimes fatal lung toxicity—completely from the regimen,” he said. “This represents a meaningful advance for this often younger patient population.”

In the phase 3 ECHELON-1 trial, researchers compared BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

In addition to supporting the new approval for BV in cHL, ECHELON-1 results also served to convert an accelerated approval of BV to standard approval. The drug now has standard FDA approval for the treatment of adults with systemic anaplastic large-cell lymphoma (ALCL) who have failed at least 1 prior multi-agent chemotherapy regimen.

BV also has standard FDA approval for:

• Adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens
• Post-auto-HSCT consolidation in adults with cHL at high risk of relapse or progression
• Adults with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared A+AVD to ABVD as frontline treatment for 1334 patients with advanced cHL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved brentuximab vedotin (ADCETRIS) in combination with chemotherapy for adults with previously untreated, stage III or IV classical Hodgkin lymphoma (cHL).

This is the fifth approved indication for BV in the US and the first regimen approved for frontline, stage III/IV cHL in the US in more than 40 years.

“The standard of care for treating newly diagnosed, advanced Hodgkin lymphoma has not changed in more than 4 decades,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective—to no avail.”

The ECHELON-1 study changed that, according to Dr Connors.

“The ECHELON-1 study results demonstrated superior efficacy of the ADCETRIS plus chemotherapy regimen, when compared to the standard of care, while removing bleomycin—an agent that can cause unpredictable and sometimes fatal lung toxicity—completely from the regimen,” he said. “This represents a meaningful advance for this often younger patient population.”

In the phase 3 ECHELON-1 trial, researchers compared BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

In addition to supporting the new approval for BV in cHL, ECHELON-1 results also served to convert an accelerated approval of BV to standard approval. The drug now has standard FDA approval for the treatment of adults with systemic anaplastic large-cell lymphoma (ALCL) who have failed at least 1 prior multi-agent chemotherapy regimen.

BV also has standard FDA approval for:

• Adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens
• Post-auto-HSCT consolidation in adults with cHL at high risk of relapse or progression
• Adults with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared A+AVD to ABVD as frontline treatment for 1334 patients with advanced cHL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved brentuximab vedotin (ADCETRIS) in combination with chemotherapy for adults with previously untreated, stage III or IV classical Hodgkin lymphoma (cHL).

This is the fifth approved indication for BV in the US and the first regimen approved for frontline, stage III/IV cHL in the US in more than 40 years.

“The standard of care for treating newly diagnosed, advanced Hodgkin lymphoma has not changed in more than 4 decades,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective—to no avail.”

The ECHELON-1 study changed that, according to Dr Connors.

“The ECHELON-1 study results demonstrated superior efficacy of the ADCETRIS plus chemotherapy regimen, when compared to the standard of care, while removing bleomycin—an agent that can cause unpredictable and sometimes fatal lung toxicity—completely from the regimen,” he said. “This represents a meaningful advance for this often younger patient population.”

In the phase 3 ECHELON-1 trial, researchers compared BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

In addition to supporting the new approval for BV in cHL, ECHELON-1 results also served to convert an accelerated approval of BV to standard approval. The drug now has standard FDA approval for the treatment of adults with systemic anaplastic large-cell lymphoma (ALCL) who have failed at least 1 prior multi-agent chemotherapy regimen.

BV also has standard FDA approval for:

• Adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens
• Post-auto-HSCT consolidation in adults with cHL at high risk of relapse or progression
• Adults with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared A+AVD to ABVD as frontline treatment for 1334 patients with advanced cHL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

Photo by Rhoda Baer

New research suggests guidelines from the National Comprehensive Cancer Network (NCCN) may sometimes be supported by low-quality evidence or no evidence at all.

Researchers compared NCCN recommendations for cancer drugs to US cancer drug approvals over a 5-year period.

Thirty-nine percent of NCCN’s treatment recommendations did not coincide with uses approved by the US Food and Drug Administration (FDA).

For most of these recommendations (84%), NCCN did not provide supporting data from randomized, phase 3 trials.

For 36% of the recommendations, NCCN gave no supporting evidence.

Vinay Prasad, MD, of Oregon Health & Science University in Portland, Oregon, and his colleagues reported these findings in The BMJ.

Dr Prasad and his colleagues compared FDA approvals of cancer drugs between 2011 and 2015 with NCCN recommendations as of March 25, 2016.

When NCCN made recommendations beyond FDA approvals, the researchers evaluated the evidence used to support those recommendations.

Forty-seven new cancer drugs were approved by the FDA for 69 indications between 2011 and 2015. NCCN recommended the 47 drugs for 113 indications, including the 69 FDA-approved indications.

So 39% (n=44) of NCCN’s recommendations were not approved by the FDA, and NCCN gave the following evidence to support these recommendations:

• No evidence—36% (n=16)
• Phase 2 trial without randomization—30% (n=13)
• Randomized, phase 3 trial—16% (n=7)
• Phase 2 trial with randomization—7% (n=3)
• Case report or series of less than 5 patients—5% (n=2)
• Book chapter or review article—2% (n=1)
• Phase 1 trial—2% (n=1)
• Ongoing trial—2% (n=1).

Dr Prasad and his colleagues did point out that not all FDA approvals are supported by randomized, phase 3 trials.

And when the team followed-up 21 months after their initial analysis, they found that 6 of the 44 (14%) additional recommendations by NCCN had received FDA approval.

The researchers also noted that they did not search for independent evidence to support NCCN recommendations beyond the references NCCN provided. So some of the recommendations may have had more or better supporting evidence than what was provided.

Still, the team said these results suggest NCCN “frequently” makes recommendations that go beyond FDA approvals and “often fails to cite evidence or relies on low levels of evidence.” Therefore, NCCN should cite all evidence used to formulate its recommendations.

NCCN argues that it does provide ample evidence to support the recommendations in its guidelines.

“The NCCN guidelines contain more than 24,500 references to inform users of the evidence used in making its decisions,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“These data are supplemented by the analysis of the available evidence by expert clinician researchers and patient advocates who evaluate each recommendation and come to consensus. Each recommendation is labeled with a Category of Evidence, and the vast majority of those for systemic therapies are accompanied by Evidence Blocks, which outline, on 1-5 scales, the efficacy, safety, quality of the evidence, consistency of the evidence, and affordability of the treatment.”

Photo by Rhoda Baer

New research suggests guidelines from the National Comprehensive Cancer Network (NCCN) may sometimes be supported by low-quality evidence or no evidence at all.

Researchers compared NCCN recommendations for cancer drugs to US cancer drug approvals over a 5-year period.

Thirty-nine percent of NCCN’s treatment recommendations did not coincide with uses approved by the US Food and Drug Administration (FDA).

For most of these recommendations (84%), NCCN did not provide supporting data from randomized, phase 3 trials.

For 36% of the recommendations, NCCN gave no supporting evidence.

Vinay Prasad, MD, of Oregon Health & Science University in Portland, Oregon, and his colleagues reported these findings in The BMJ.

Dr Prasad and his colleagues compared FDA approvals of cancer drugs between 2011 and 2015 with NCCN recommendations as of March 25, 2016.

When NCCN made recommendations beyond FDA approvals, the researchers evaluated the evidence used to support those recommendations.

Forty-seven new cancer drugs were approved by the FDA for 69 indications between 2011 and 2015. NCCN recommended the 47 drugs for 113 indications, including the 69 FDA-approved indications.

So 39% (n=44) of NCCN’s recommendations were not approved by the FDA, and NCCN gave the following evidence to support these recommendations:

• No evidence—36% (n=16)
• Phase 2 trial without randomization—30% (n=13)
• Randomized, phase 3 trial—16% (n=7)
• Phase 2 trial with randomization—7% (n=3)
• Case report or series of less than 5 patients—5% (n=2)
• Book chapter or review article—2% (n=1)
• Phase 1 trial—2% (n=1)
• Ongoing trial—2% (n=1).

Dr Prasad and his colleagues did point out that not all FDA approvals are supported by randomized, phase 3 trials.

And when the team followed-up 21 months after their initial analysis, they found that 6 of the 44 (14%) additional recommendations by NCCN had received FDA approval.

The researchers also noted that they did not search for independent evidence to support NCCN recommendations beyond the references NCCN provided. So some of the recommendations may have had more or better supporting evidence than what was provided.

Still, the team said these results suggest NCCN “frequently” makes recommendations that go beyond FDA approvals and “often fails to cite evidence or relies on low levels of evidence.” Therefore, NCCN should cite all evidence used to formulate its recommendations.

NCCN argues that it does provide ample evidence to support the recommendations in its guidelines.

“The NCCN guidelines contain more than 24,500 references to inform users of the evidence used in making its decisions,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“These data are supplemented by the analysis of the available evidence by expert clinician researchers and patient advocates who evaluate each recommendation and come to consensus. Each recommendation is labeled with a Category of Evidence, and the vast majority of those for systemic therapies are accompanied by Evidence Blocks, which outline, on 1-5 scales, the efficacy, safety, quality of the evidence, consistency of the evidence, and affordability of the treatment.”

Photo by Rhoda Baer

New research suggests guidelines from the National Comprehensive Cancer Network (NCCN) may sometimes be supported by low-quality evidence or no evidence at all.

Researchers compared NCCN recommendations for cancer drugs to US cancer drug approvals over a 5-year period.

Thirty-nine percent of NCCN’s treatment recommendations did not coincide with uses approved by the US Food and Drug Administration (FDA).

For most of these recommendations (84%), NCCN did not provide supporting data from randomized, phase 3 trials.

For 36% of the recommendations, NCCN gave no supporting evidence.

Vinay Prasad, MD, of Oregon Health & Science University in Portland, Oregon, and his colleagues reported these findings in The BMJ.

Dr Prasad and his colleagues compared FDA approvals of cancer drugs between 2011 and 2015 with NCCN recommendations as of March 25, 2016.

When NCCN made recommendations beyond FDA approvals, the researchers evaluated the evidence used to support those recommendations.

Forty-seven new cancer drugs were approved by the FDA for 69 indications between 2011 and 2015. NCCN recommended the 47 drugs for 113 indications, including the 69 FDA-approved indications.

So 39% (n=44) of NCCN’s recommendations were not approved by the FDA, and NCCN gave the following evidence to support these recommendations:

• No evidence—36% (n=16)
• Phase 2 trial without randomization—30% (n=13)
• Randomized, phase 3 trial—16% (n=7)
• Phase 2 trial with randomization—7% (n=3)
• Case report or series of less than 5 patients—5% (n=2)
• Book chapter or review article—2% (n=1)
• Phase 1 trial—2% (n=1)
• Ongoing trial—2% (n=1).

Dr Prasad and his colleagues did point out that not all FDA approvals are supported by randomized, phase 3 trials.

And when the team followed-up 21 months after their initial analysis, they found that 6 of the 44 (14%) additional recommendations by NCCN had received FDA approval.

The researchers also noted that they did not search for independent evidence to support NCCN recommendations beyond the references NCCN provided. So some of the recommendations may have had more or better supporting evidence than what was provided.

Still, the team said these results suggest NCCN “frequently” makes recommendations that go beyond FDA approvals and “often fails to cite evidence or relies on low levels of evidence.” Therefore, NCCN should cite all evidence used to formulate its recommendations.

NCCN argues that it does provide ample evidence to support the recommendations in its guidelines.

“The NCCN guidelines contain more than 24,500 references to inform users of the evidence used in making its decisions,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“These data are supplemented by the analysis of the available evidence by expert clinician researchers and patient advocates who evaluate each recommendation and come to consensus. Each recommendation is labeled with a Category of Evidence, and the vast majority of those for systemic therapies are accompanied by Evidence Blocks, which outline, on 1-5 scales, the efficacy, safety, quality of the evidence, consistency of the evidence, and affordability of the treatment.”

Photo from Business Wire

The US Food and Drug Administration (FDA) has updated the label for nivolumab (Opdivo®) to include new dosing and administration information.

Nivolumab can now be given at 480 mg infused every 4 weeks for most approved indications, in addition to the previously approved dosing schedule of 240 mg every 2 weeks.

The FDA also approved a shorter 30-minute infusion across all approved indications of nivolumab.

The 480 mg dose option can be used for nearly all approved indications of nivolumab. The exceptions are patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer.

Nivolumab is FDA-approved for the following indications:

• To treat adults with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT.
• As monotherapy for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma as well as BRAF V600 wild-type unresectable or metastatic melanoma.
• In combination with ipilimumab for the treatment of patients with unresectable or metastatic melanoma.
• To treat patients with metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab.
• For patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
• To treat patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy.
• For patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or after platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• To treat adult and pediatric (12 years and older) patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
• For patients with hepatocellular carcinoma who have been previously treated with sorafenib.
• For the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

Photo from Business Wire

The US Food and Drug Administration (FDA) has updated the label for nivolumab (Opdivo®) to include new dosing and administration information.

Nivolumab can now be given at 480 mg infused every 4 weeks for most approved indications, in addition to the previously approved dosing schedule of 240 mg every 2 weeks.

The FDA also approved a shorter 30-minute infusion across all approved indications of nivolumab.

The 480 mg dose option can be used for nearly all approved indications of nivolumab. The exceptions are patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer.

Nivolumab is FDA-approved for the following indications:

• To treat adults with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT.
• As monotherapy for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma as well as BRAF V600 wild-type unresectable or metastatic melanoma.
• In combination with ipilimumab for the treatment of patients with unresectable or metastatic melanoma.
• To treat patients with metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab.
• For patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
• To treat patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy.
• For patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or after platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• To treat adult and pediatric (12 years and older) patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
• For patients with hepatocellular carcinoma who have been previously treated with sorafenib.
• For the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

Photo from Business Wire

The US Food and Drug Administration (FDA) has updated the label for nivolumab (Opdivo®) to include new dosing and administration information.

Nivolumab can now be given at 480 mg infused every 4 weeks for most approved indications, in addition to the previously approved dosing schedule of 240 mg every 2 weeks.

The FDA also approved a shorter 30-minute infusion across all approved indications of nivolumab.

The 480 mg dose option can be used for nearly all approved indications of nivolumab. The exceptions are patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer.

Nivolumab is FDA-approved for the following indications:

• To treat adults with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT.
• As monotherapy for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma as well as BRAF V600 wild-type unresectable or metastatic melanoma.
• In combination with ipilimumab for the treatment of patients with unresectable or metastatic melanoma.
• To treat patients with metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab.
• For patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
• To treat patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy.
• For patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or after platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• To treat adult and pediatric (12 years and older) patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
• For patients with hepatocellular carcinoma who have been previously treated with sorafenib.
• For the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.