Pharmacy

Photo courtesy of Celgene

The China Food and Drug Administration (CFDA) has approved lenalidomide (Revlimid®) to treat patients with newly diagnosed multiple myeloma (MM).

The drug is now approved for use in combination with dexamethasone to treat adults with previously untreated MM who are not eligible for transplant.

Lenalidomide was first approved by the CFDA in 2013 for use in combination with dexamethasone to treat adults with MM who had received at least one prior therapy.

“In China, where the incidence of multiple myeloma is on the rise due to an aging population and improved diagnosis, we are hopeful that newly diagnosed patients will have a meaningful long-term benefit from this approval,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene, the company marketing lenalidomide as Revlimid in China under an exclusive license from Celgene Corporation.

Trial results

The CFDA’s decision to expand the approval of lenalidomide is based on results from the phase 3 FIRST trial. Updated results from this study were published in the Journal of Clinical Oncology in November 2016.

The trial included 1623 patients with newly diagnosed MM who were not eligible for stem cell transplant.

Patients were randomized to receive:

• Lenalidomide and low-dose dexamethasone (Rd) in 28-day cycles until disease progression (n=535), known as the “continuous Rd group”
• 18 cycles of Rd (Rd18) for 72 weeks (n=541), known as the “Rd18 group”
• Melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.

The median progression-free survival was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, progression-free survival rates were 33%, 14%, and 13%, respectively.

The median overall survival was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, overall survival rates were 60%, 57%, and 51%, respectively.

The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.

Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.

Photo courtesy of Celgene

The China Food and Drug Administration (CFDA) has approved lenalidomide (Revlimid®) to treat patients with newly diagnosed multiple myeloma (MM).

The drug is now approved for use in combination with dexamethasone to treat adults with previously untreated MM who are not eligible for transplant.

Lenalidomide was first approved by the CFDA in 2013 for use in combination with dexamethasone to treat adults with MM who had received at least one prior therapy.

“In China, where the incidence of multiple myeloma is on the rise due to an aging population and improved diagnosis, we are hopeful that newly diagnosed patients will have a meaningful long-term benefit from this approval,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene, the company marketing lenalidomide as Revlimid in China under an exclusive license from Celgene Corporation.

Trial results

The CFDA’s decision to expand the approval of lenalidomide is based on results from the phase 3 FIRST trial. Updated results from this study were published in the Journal of Clinical Oncology in November 2016.

The trial included 1623 patients with newly diagnosed MM who were not eligible for stem cell transplant.

Patients were randomized to receive:

• Lenalidomide and low-dose dexamethasone (Rd) in 28-day cycles until disease progression (n=535), known as the “continuous Rd group”
• 18 cycles of Rd (Rd18) for 72 weeks (n=541), known as the “Rd18 group”
• Melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.

The median progression-free survival was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, progression-free survival rates were 33%, 14%, and 13%, respectively.

The median overall survival was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, overall survival rates were 60%, 57%, and 51%, respectively.

The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.

Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.

Photo courtesy of Celgene

The China Food and Drug Administration (CFDA) has approved lenalidomide (Revlimid®) to treat patients with newly diagnosed multiple myeloma (MM).

The drug is now approved for use in combination with dexamethasone to treat adults with previously untreated MM who are not eligible for transplant.

Lenalidomide was first approved by the CFDA in 2013 for use in combination with dexamethasone to treat adults with MM who had received at least one prior therapy.

“In China, where the incidence of multiple myeloma is on the rise due to an aging population and improved diagnosis, we are hopeful that newly diagnosed patients will have a meaningful long-term benefit from this approval,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene, the company marketing lenalidomide as Revlimid in China under an exclusive license from Celgene Corporation.

Trial results

The CFDA’s decision to expand the approval of lenalidomide is based on results from the phase 3 FIRST trial. Updated results from this study were published in the Journal of Clinical Oncology in November 2016.

The trial included 1623 patients with newly diagnosed MM who were not eligible for stem cell transplant.

Patients were randomized to receive:

• Lenalidomide and low-dose dexamethasone (Rd) in 28-day cycles until disease progression (n=535), known as the “continuous Rd group”
• 18 cycles of Rd (Rd18) for 72 weeks (n=541), known as the “Rd18 group”
• Melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.

The median progression-free survival was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, progression-free survival rates were 33%, 14%, and 13%, respectively.

The median overall survival was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, overall survival rates were 60%, 57%, and 51%, respectively.

The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.

Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.

Photo from Business Wire

The European Commission (EC) has granted marketing authorization for emicizumab (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.

This means emicizumab is approved for use in the European Union for routine prophylaxis of bleeding episodes in patients of all ages who have hemophilia A and factor VIII inhibitors.

The recommended dose of emicizumab is 3 mg/kg once a week for the first 4 weeks, followed by 1.5 mg/kg once a week.

Emicizumab is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for patients with hemophilia A.

Emicizumab was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche, and Genentech.

The EC’s decision to authorize marketing of emicizumab is based on results 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), and 3 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

The European Commission (EC) has granted marketing authorization for emicizumab (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.

This means emicizumab is approved for use in the European Union for routine prophylaxis of bleeding episodes in patients of all ages who have hemophilia A and factor VIII inhibitors.

The recommended dose of emicizumab is 3 mg/kg once a week for the first 4 weeks, followed by 1.5 mg/kg once a week.

Emicizumab is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for patients with hemophilia A.

Emicizumab was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche, and Genentech.

The EC’s decision to authorize marketing of emicizumab is based on results 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), and 3 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

The European Commission (EC) has granted marketing authorization for emicizumab (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.

This means emicizumab is approved for use in the European Union for routine prophylaxis of bleeding episodes in patients of all ages who have hemophilia A and factor VIII inhibitors.

The recommended dose of emicizumab is 3 mg/kg once a week for the first 4 weeks, followed by 1.5 mg/kg once a week.

Emicizumab is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for patients with hemophilia A.

Emicizumab was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche, and Genentech.

The EC’s decision to authorize marketing of emicizumab is based on results 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), and 3 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.

AML cells

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for gemtuzumab ozogamicin (GO, Mylotarg™).

The recommendation is for GO to be used in combination with daunorubicin and cytarabine to treat patients age 15 years and older with previously untreated, de novo, CD33-positive acute myeloid leukemia (AML) but not acute promyelocytic leukemia.

The CHMP’s opinion on GO 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.

Previous rejection

The CHMP previously issued a negative opinion of GO (first in 2007, confirmed in 2008), saying the drug should not receive marketing authorization.

The proposed indication for GO at that time was as re-induction treatment in adults with CD33-positive AML in first relapse who were not candidates for other intensive re-induction chemotherapy regimens and were either older than 60 or had a duration of first remission lasting less than 12 months.

The CHMP said there was insufficient evidence to establish the effectiveness of GO in AML, and the drug’s benefits did not outweigh its risks.

Phase 3 trial

The current marketing authorization application for GO is supported by data from an investigator-led, phase 3, randomized trial known as ALFA-0701. Updated results from this trial are available in the US prescribing information for GO.

Patients and treatment

ALFA-0701 included 271 patients with newly diagnosed, de novo AML who were 50 to 70 years of age.

Patients were randomized (1:1) to receive induction consisting of daunorubicin (60 mg/m² on days 1 to 3) and cytarabine (200 mg/m² on days 1 to 7) with (n=135) or without (n=136) GO at 3 mg/m² (up to maximum of 1 vial) on days 1, 4, and 7. Patients who did not achieve a response after first induction could receive a second induction with daunorubicin and cytarabine alone.

Patients with a response received consolidation therapy with 2 courses of treatment including daunorubicin (60 mg/m² on day 1 of first consolidation course; 60 mg/m² on days 1 and 2 of second consolidation course) and cytarabine (1 g/m² every 12 hours on days 1 to 4) with or without GO at 3 mg/m² (up to a maximum of 1 vial) on day 1 according to their initial randomization.

Patients who achieved remission were also eligible for allogeneic transplant. An interval of at least 2 months between the last dose of GO and transplant was recommended.

Baseline characteristics were largely well balanced between the treatment arms, but there was a higher percentage of males in the GO arm than the control arm—55% and 44%, respectively.

Results

The study’s primary endpoint was event-free survival. The median event-free survival was 17.3 months in the GO arm and 9.5 months in the control arm (hazard ratio=0.56; 95% CI: 0.42-0.76; P<0.001).

There was no significant difference in overall survival between the treatment arms. (Updated overall survival data have not been provided).

All patients in this trial developed severe neutropenia, thrombocytopenia, and anemia. However, the incidence of prolonged, grade 3–4 thrombocytopenia in the absence of active leukemia was higher in the GO arm.

Treatment-emergent adverse events (AEs) considered most important for understanding the safety profile of GO were hemorrhage, veno-occlusive liver disease (VOD), and severe infections.

Treatment discontinuation due to any AE occurred in 31% of patients in the GO arm and 7% of those in the control arm. The most frequent AEs leading to discontinuation for patients on GO were thrombocytopenia (15%), VOD (3%), and septic shock (2%).

Fatal AEs occurred in 8 patients (6%) in the GO arm and 3 (2%) in the control arm. In the GO arm, 3 patients died of VOD, 4 died of hemorrhage-related events, and 1 died of a suspected cardiac cause. All 3 fatal AEs in the control arm were sepsis.

AML cells

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for gemtuzumab ozogamicin (GO, Mylotarg™).

The recommendation is for GO to be used in combination with daunorubicin and cytarabine to treat patients age 15 years and older with previously untreated, de novo, CD33-positive acute myeloid leukemia (AML) but not acute promyelocytic leukemia.

The CHMP’s opinion on GO 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.

Previous rejection

The CHMP previously issued a negative opinion of GO (first in 2007, confirmed in 2008), saying the drug should not receive marketing authorization.

The proposed indication for GO at that time was as re-induction treatment in adults with CD33-positive AML in first relapse who were not candidates for other intensive re-induction chemotherapy regimens and were either older than 60 or had a duration of first remission lasting less than 12 months.

The CHMP said there was insufficient evidence to establish the effectiveness of GO in AML, and the drug’s benefits did not outweigh its risks.

Phase 3 trial

The current marketing authorization application for GO is supported by data from an investigator-led, phase 3, randomized trial known as ALFA-0701. Updated results from this trial are available in the US prescribing information for GO.

Patients and treatment

ALFA-0701 included 271 patients with newly diagnosed, de novo AML who were 50 to 70 years of age.

Patients were randomized (1:1) to receive induction consisting of daunorubicin (60 mg/m² on days 1 to 3) and cytarabine (200 mg/m² on days 1 to 7) with (n=135) or without (n=136) GO at 3 mg/m² (up to maximum of 1 vial) on days 1, 4, and 7. Patients who did not achieve a response after first induction could receive a second induction with daunorubicin and cytarabine alone.

Patients with a response received consolidation therapy with 2 courses of treatment including daunorubicin (60 mg/m² on day 1 of first consolidation course; 60 mg/m² on days 1 and 2 of second consolidation course) and cytarabine (1 g/m² every 12 hours on days 1 to 4) with or without GO at 3 mg/m² (up to a maximum of 1 vial) on day 1 according to their initial randomization.

Patients who achieved remission were also eligible for allogeneic transplant. An interval of at least 2 months between the last dose of GO and transplant was recommended.

Baseline characteristics were largely well balanced between the treatment arms, but there was a higher percentage of males in the GO arm than the control arm—55% and 44%, respectively.

Results

The study’s primary endpoint was event-free survival. The median event-free survival was 17.3 months in the GO arm and 9.5 months in the control arm (hazard ratio=0.56; 95% CI: 0.42-0.76; P<0.001).

There was no significant difference in overall survival between the treatment arms. (Updated overall survival data have not been provided).

All patients in this trial developed severe neutropenia, thrombocytopenia, and anemia. However, the incidence of prolonged, grade 3–4 thrombocytopenia in the absence of active leukemia was higher in the GO arm.

Treatment-emergent adverse events (AEs) considered most important for understanding the safety profile of GO were hemorrhage, veno-occlusive liver disease (VOD), and severe infections.

Treatment discontinuation due to any AE occurred in 31% of patients in the GO arm and 7% of those in the control arm. The most frequent AEs leading to discontinuation for patients on GO were thrombocytopenia (15%), VOD (3%), and septic shock (2%).

Fatal AEs occurred in 8 patients (6%) in the GO arm and 3 (2%) in the control arm. In the GO arm, 3 patients died of VOD, 4 died of hemorrhage-related events, and 1 died of a suspected cardiac cause. All 3 fatal AEs in the control arm were sepsis.

AML cells

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for gemtuzumab ozogamicin (GO, Mylotarg™).

The recommendation is for GO to be used in combination with daunorubicin and cytarabine to treat patients age 15 years and older with previously untreated, de novo, CD33-positive acute myeloid leukemia (AML) but not acute promyelocytic leukemia.

The CHMP’s opinion on GO 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.

Previous rejection

The CHMP previously issued a negative opinion of GO (first in 2007, confirmed in 2008), saying the drug should not receive marketing authorization.

The proposed indication for GO at that time was as re-induction treatment in adults with CD33-positive AML in first relapse who were not candidates for other intensive re-induction chemotherapy regimens and were either older than 60 or had a duration of first remission lasting less than 12 months.

The CHMP said there was insufficient evidence to establish the effectiveness of GO in AML, and the drug’s benefits did not outweigh its risks.

Phase 3 trial

The current marketing authorization application for GO is supported by data from an investigator-led, phase 3, randomized trial known as ALFA-0701. Updated results from this trial are available in the US prescribing information for GO.

Patients and treatment

ALFA-0701 included 271 patients with newly diagnosed, de novo AML who were 50 to 70 years of age.

Patients were randomized (1:1) to receive induction consisting of daunorubicin (60 mg/m² on days 1 to 3) and cytarabine (200 mg/m² on days 1 to 7) with (n=135) or without (n=136) GO at 3 mg/m² (up to maximum of 1 vial) on days 1, 4, and 7. Patients who did not achieve a response after first induction could receive a second induction with daunorubicin and cytarabine alone.

Patients with a response received consolidation therapy with 2 courses of treatment including daunorubicin (60 mg/m² on day 1 of first consolidation course; 60 mg/m² on days 1 and 2 of second consolidation course) and cytarabine (1 g/m² every 12 hours on days 1 to 4) with or without GO at 3 mg/m² (up to a maximum of 1 vial) on day 1 according to their initial randomization.

Patients who achieved remission were also eligible for allogeneic transplant. An interval of at least 2 months between the last dose of GO and transplant was recommended.

Baseline characteristics were largely well balanced between the treatment arms, but there was a higher percentage of males in the GO arm than the control arm—55% and 44%, respectively.

Results

The study’s primary endpoint was event-free survival. The median event-free survival was 17.3 months in the GO arm and 9.5 months in the control arm (hazard ratio=0.56; 95% CI: 0.42-0.76; P<0.001).

There was no significant difference in overall survival between the treatment arms. (Updated overall survival data have not been provided).

All patients in this trial developed severe neutropenia, thrombocytopenia, and anemia. However, the incidence of prolonged, grade 3–4 thrombocytopenia in the absence of active leukemia was higher in the GO arm.

Treatment-emergent adverse events (AEs) considered most important for understanding the safety profile of GO were hemorrhage, veno-occlusive liver disease (VOD), and severe infections.

Treatment discontinuation due to any AE occurred in 31% of patients in the GO arm and 7% of those in the control arm. The most frequent AEs leading to discontinuation for patients on GO were thrombocytopenia (15%), VOD (3%), and septic shock (2%).

Fatal AEs occurred in 8 patients (6%) in the GO arm and 3 (2%) in the control arm. In the GO arm, 3 patients died of VOD, 4 died of hemorrhage-related events, and 1 died of a suspected cardiac cause. All 3 fatal AEs in the control arm were sepsis.

Gilead Sciences, Inc.

Gilead Sciences International Ltd. recently withdrew its application for European approval of idelalisib (Zydelig) in combination with rituximab and bendamustine for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL).

Idelalisib is currently approved in the European Union for use in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment of CLL in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies.

Idelalisib is also approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

In seeking expanded approval for idelalisib, Gilead submitted data from a study (NCT01569295) comparing idelalisib plus bendamustine and rituximab to placebo plus bendamustine and rituximab.

Interim results from this study were published in The Lancet Oncology in March 2017.

Gilead withdrew the application for idelalisib after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) had evaluated documentation provided by the company and formulated lists of questions.

Gilead had not responded to the last round of questions at the time of the withdrawal.

At that point, the CHMP was of the provisional opinion that idelalisib should not be approved for use in combination with rituximab and bendamustine in patients with relapsed/refractory CLL.

The CHMP said additional, longer-term data are needed to show the benefits of idelalisib plus rituximab and bendamustine outweigh the risks.

Gilead said its withdrawal of the application was based on the CHMP’s opinion that there was insufficient evidence of a favorable benefit-risk profile.

The company also said the withdrawal does not impact ongoing trials of idelalisib.

Gilead Sciences, Inc.

Gilead Sciences International Ltd. recently withdrew its application for European approval of idelalisib (Zydelig) in combination with rituximab and bendamustine for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL).

Idelalisib is currently approved in the European Union for use in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment of CLL in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies.

Idelalisib is also approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

In seeking expanded approval for idelalisib, Gilead submitted data from a study (NCT01569295) comparing idelalisib plus bendamustine and rituximab to placebo plus bendamustine and rituximab.

Interim results from this study were published in The Lancet Oncology in March 2017.

Gilead withdrew the application for idelalisib after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) had evaluated documentation provided by the company and formulated lists of questions.

Gilead had not responded to the last round of questions at the time of the withdrawal.

At that point, the CHMP was of the provisional opinion that idelalisib should not be approved for use in combination with rituximab and bendamustine in patients with relapsed/refractory CLL.

The CHMP said additional, longer-term data are needed to show the benefits of idelalisib plus rituximab and bendamustine outweigh the risks.

Gilead said its withdrawal of the application was based on the CHMP’s opinion that there was insufficient evidence of a favorable benefit-risk profile.

The company also said the withdrawal does not impact ongoing trials of idelalisib.

Gilead Sciences, Inc.

Gilead Sciences International Ltd. recently withdrew its application for European approval of idelalisib (Zydelig) in combination with rituximab and bendamustine for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL).

Idelalisib is currently approved in the European Union for use in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment of CLL in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies.

Idelalisib is also approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

In seeking expanded approval for idelalisib, Gilead submitted data from a study (NCT01569295) comparing idelalisib plus bendamustine and rituximab to placebo plus bendamustine and rituximab.

Interim results from this study were published in The Lancet Oncology in March 2017.

Gilead withdrew the application for idelalisib after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) had evaluated documentation provided by the company and formulated lists of questions.

Gilead had not responded to the last round of questions at the time of the withdrawal.

At that point, the CHMP was of the provisional opinion that idelalisib should not be approved for use in combination with rituximab and bendamustine in patients with relapsed/refractory CLL.

The CHMP said additional, longer-term data are needed to show the benefits of idelalisib plus rituximab and bendamustine outweigh the risks.

Gilead said its withdrawal of the application was based on the CHMP’s opinion that there was insufficient evidence of a favorable benefit-risk profile.

The company also said the withdrawal does not impact ongoing trials of idelalisib.

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended a label variation for Neulasta® (pegfilgrastim) to include the Neulasta® Onpro® Kit.

The Neulasta Onpro Kit is an on-body injector (OBI) delivery system for Neulasta, which is approved in the European Union to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).

The Neulasta Onpro Kit includes a specifically designed Neulasta pre-filled syringe along with a single-use OBI. The small, lightweight OBI is applied to a patient’s skin on the same day of chemotherapy.

The OBI is intended to facilitate timed delivery of the correct dose of Neulasta and eliminate the need for patients to return to a healthcare setting the day after they receive chemotherapy.

The CHMP’s opinion on the Neulasta Onpro Kit will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the centralized marketing authorization of Neulasta will be updated to include information on the Neulasta Onpro Kit in the drug’s label.

This change will be valid throughout the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions about Neulasta’s label on the basis of the EC’s decision.

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

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended a label variation for Neulasta® (pegfilgrastim) to include the Neulasta® Onpro® Kit.

The Neulasta Onpro Kit is an on-body injector (OBI) delivery system for Neulasta, which is approved in the European Union to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).

The Neulasta Onpro Kit includes a specifically designed Neulasta pre-filled syringe along with a single-use OBI. The small, lightweight OBI is applied to a patient’s skin on the same day of chemotherapy.

The OBI is intended to facilitate timed delivery of the correct dose of Neulasta and eliminate the need for patients to return to a healthcare setting the day after they receive chemotherapy.

The CHMP’s opinion on the Neulasta Onpro Kit will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the centralized marketing authorization of Neulasta will be updated to include information on the Neulasta Onpro Kit in the drug’s label.

This change will be valid throughout the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions about Neulasta’s label on the basis of the EC’s decision.

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

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended a label variation for Neulasta® (pegfilgrastim) to include the Neulasta® Onpro® Kit.

The Neulasta Onpro Kit is an on-body injector (OBI) delivery system for Neulasta, which is approved in the European Union to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).

The Neulasta Onpro Kit includes a specifically designed Neulasta pre-filled syringe along with a single-use OBI. The small, lightweight OBI is applied to a patient’s skin on the same day of chemotherapy.

The OBI is intended to facilitate timed delivery of the correct dose of Neulasta and eliminate the need for patients to return to a healthcare setting the day after they receive chemotherapy.

The CHMP’s opinion on the Neulasta Onpro Kit will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the centralized marketing authorization of Neulasta will be updated to include information on the Neulasta Onpro Kit in the drug’s label.

This change will be valid throughout the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions about Neulasta’s label on the basis of the EC’s decision.

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

Image by Difu Wu

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved use of bosutinib (BOSULIF) to include treatment of patients with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

Bosutinib is currently approved in Europe to treat patients with Ph+ CML in chronic, accelerated, or blast phase who have received one or more tyrosine kinase inhibitors and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options.

The CHMP’s opinion on bosutinib 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.

The CHMP’s recommendation for bosutinib is based on results from the BFORE trial, which were recently published in the Journal of Clinical Oncology.

The publication included data on 536 patients newly diagnosed with chronic phase CML. They were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).

The modified intent-to-treat population included Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.

In the modified intent-to-treat population, the rate of major molecular response at 12 months was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).

In the entire study population, 22.0% of patients receiving bosutinib and 26.8% of those receiving imatinib discontinued treatment—12.7% and 8.7%, respectively, due to drug-related toxicity.

Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).

Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).

Image by Difu Wu

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved use of bosutinib (BOSULIF) to include treatment of patients with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

Bosutinib is currently approved in Europe to treat patients with Ph+ CML in chronic, accelerated, or blast phase who have received one or more tyrosine kinase inhibitors and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options.

The CHMP’s opinion on bosutinib 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.

The CHMP’s recommendation for bosutinib is based on results from the BFORE trial, which were recently published in the Journal of Clinical Oncology.

The publication included data on 536 patients newly diagnosed with chronic phase CML. They were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).

The modified intent-to-treat population included Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.

In the modified intent-to-treat population, the rate of major molecular response at 12 months was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).

In the entire study population, 22.0% of patients receiving bosutinib and 26.8% of those receiving imatinib discontinued treatment—12.7% and 8.7%, respectively, due to drug-related toxicity.

Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).

Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).

Image by Difu Wu

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved use of bosutinib (BOSULIF) to include treatment of patients with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

Bosutinib is currently approved in Europe to treat patients with Ph+ CML in chronic, accelerated, or blast phase who have received one or more tyrosine kinase inhibitors and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options.

The CHMP’s opinion on bosutinib 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.

The CHMP’s recommendation for bosutinib is based on results from the BFORE trial, which were recently published in the Journal of Clinical Oncology.

The publication included data on 536 patients newly diagnosed with chronic phase CML. They were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).

The modified intent-to-treat population included Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.

In the modified intent-to-treat population, the rate of major molecular response at 12 months was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).

In the entire study population, 22.0% of patients receiving bosutinib and 26.8% of those receiving imatinib discontinued treatment—12.7% and 8.7%, respectively, due to drug-related toxicity.

Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).

Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the current indication for denosumab (XGEVA®).

The CHMP said the drug should be approved for use in preventing skeletal related events (SREs) in adults with advanced malignancies involving bone, which includes multiple myeloma (MM).

Denosumab is currently approved in Europe to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.

The drug is also approved for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

The CHMP’s opinion on expanding the indication for denosumab 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.

The CHMP’s recommendation for denosumab is based on data from the ’482 study, which were recently published in The Lancet Oncology.

In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.

Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859). All patients also received investigators’ choice of first-line MM therapy.

The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P non-inferiority=0.010).

There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.

But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the current indication for denosumab (XGEVA®).

The CHMP said the drug should be approved for use in preventing skeletal related events (SREs) in adults with advanced malignancies involving bone, which includes multiple myeloma (MM).

Denosumab is currently approved in Europe to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.

The drug is also approved for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

The CHMP’s opinion on expanding the indication for denosumab 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.

The CHMP’s recommendation for denosumab is based on data from the ’482 study, which were recently published in The Lancet Oncology.

In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.

Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859). All patients also received investigators’ choice of first-line MM therapy.

The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P non-inferiority=0.010).

There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.

But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the current indication for denosumab (XGEVA®).

The CHMP said the drug should be approved for use in preventing skeletal related events (SREs) in adults with advanced malignancies involving bone, which includes multiple myeloma (MM).

Denosumab is currently approved in Europe to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.

The drug is also approved for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

The CHMP’s opinion on expanding the indication for denosumab 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.

The CHMP’s recommendation for denosumab is based on data from the ’482 study, which were recently published in The Lancet Oncology.

In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.

Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859). All patients also received investigators’ choice of first-line MM therapy.

The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P non-inferiority=0.010).

There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.

But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.

showing MM

The US Food and Drug Administration (FDA) has granted orphan designation to PT-112 as a treatment for multiple myeloma (MM).

PT-112 is a small-molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage-associated molecular patterns, leading to downstream T-cell recruitment in the tumor microenvironment.

PT-112 is currently under investigation in a phase 1/2 study of patients with relapsed or refractory MM (NCT03288480).

Phosplatin Therapeutics LLC, the company developing PT-112, has enrolled the first cohort of patients in this trial.

In preclinical experiments, PT-112 demonstrated synergy with lenalidomide and bortezomib in RPMI-8226 cells and dexamethasone-resistant MM1R cells.

Single-agent PT-112 produced responses in mice with established MM. Researchers said PT-112 had “pronounced” activity against bortezomib-refractory Vk12598 tumors, which significantly improved overall survival in the mice.

This research was presented at the 2017 ASH Annual Meeting (abstract 1797).

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.

showing MM

The US Food and Drug Administration (FDA) has granted orphan designation to PT-112 as a treatment for multiple myeloma (MM).

PT-112 is a small-molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage-associated molecular patterns, leading to downstream T-cell recruitment in the tumor microenvironment.

PT-112 is currently under investigation in a phase 1/2 study of patients with relapsed or refractory MM (NCT03288480).

Phosplatin Therapeutics LLC, the company developing PT-112, has enrolled the first cohort of patients in this trial.

In preclinical experiments, PT-112 demonstrated synergy with lenalidomide and bortezomib in RPMI-8226 cells and dexamethasone-resistant MM1R cells.

Single-agent PT-112 produced responses in mice with established MM. Researchers said PT-112 had “pronounced” activity against bortezomib-refractory Vk12598 tumors, which significantly improved overall survival in the mice.

This research was presented at the 2017 ASH Annual Meeting (abstract 1797).

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.

showing MM

The US Food and Drug Administration (FDA) has granted orphan designation to PT-112 as a treatment for multiple myeloma (MM).

PT-112 is a small-molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage-associated molecular patterns, leading to downstream T-cell recruitment in the tumor microenvironment.

PT-112 is currently under investigation in a phase 1/2 study of patients with relapsed or refractory MM (NCT03288480).

Phosplatin Therapeutics LLC, the company developing PT-112, has enrolled the first cohort of patients in this trial.

In preclinical experiments, PT-112 demonstrated synergy with lenalidomide and bortezomib in RPMI-8226 cells and dexamethasone-resistant MM1R cells.

Single-agent PT-112 produced responses in mice with established MM. Researchers said PT-112 had “pronounced” activity against bortezomib-refractory Vk12598 tumors, which significantly improved overall survival in the mice.

This research was presented at the 2017 ASH Annual Meeting (abstract 1797).

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 Novo Nordisk

The recombinant, GlycoPEGylated coagulation factor IX product Rebinyn® is now available in the US for the treatment of patients with hemophilia B.

Last May, Rebinyn was approved by the US Food and Drug Administration for on-demand treatment and control of bleeding episodes as well as perioperative management of bleeding in adults and children with hemophilia B.

The product is not approved for routine prophylaxis or immune tolerance induction in hemophilia B patients.

The full prescribing information is available at www.Rebinyn.com.

Rebinyn is also approved for use in the European Union, where it is known as nonacog beta pegol or by the brand name Refixia.

There, the product is approved for use as prophylaxis, for on-demand treatment of bleeding, and for control of bleeding related to surgical procedures in adolescents (older than 12 years of age) and adults with hemophilia B.

Trial results

The US and European approvals of nonacog beta pegol (N9-GP) were based on results from the paradigm™ clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.

Paradigm 4 was an extension trial enrolling patients who had participated in the phase 3 trials paradigm 2 and paradigm 3.

In paradigm 2, researchers assessed N9-GP as treatment and prophylaxis in previously treated patients with hemophilia B. In paradigm 3, researchers assessed N9-GP in hemophilia B patients undergoing surgical procedures.

Paradigm 4 included 71 patients (ages 13 to 70) who continued to receive N9-GP as on-demand treatment (40 IU/kg for mild/moderate bleeds and 80 IU/kg for severe bleeds) or prophylaxis (10 IU/kg or 40 IU/kg once-weekly). Sixty-five patients completed treatment.

Safety

None of the patients developed factor IX inhibitors. Two patients had transient binding antibodies to N9-GP, but there was no sign that these antibodies had an inhibitory effect.

Four patients developed anti-CHO antibodies, but only 2 of these patients were still positive for these antibodies at the end of the trial.

There were a total of 155 adverse events. However, only 4 of these (in 3 patients) were considered possibly or probably related to N9-GP.

These events consisted of an injection site rash in 1 patient, 2 overdoses in 1 patient, and neutropenia in 1 patient. The rash and neutropenia resolved, and the patient who overdosed recovered without complications.

Efficacy

The researchers said the success rate for the treatment of reported bleeds was 94.6%. Most bleeds (87.9%) were resolved with a single injection of N9-GP, but 9.2% required 2 injections, and 2.9% required 3 or 4 injections.

The median annualized bleeding rate for patients on prophylaxis was 1.05 (interquartile range [IQR], 0.00–2.20) overall. It was 1.36 (IQR, 0.00-2.23) for the 10 IU/kg arm and 1.00 (IQR, 0.00-2.03) for the 40 IU/kg arm.

There were 14 patients on prophylaxis who underwent 23 minor surgical procedures.

The hemostatic response was considered “excellent” (better than expected/predicted for the procedure in question) in 19 procedures and “good” (as expected) in 2 procedures. In the remaining 2 procedures, hemostatic responses were not determined.

Photo from Novo Nordisk

The recombinant, GlycoPEGylated coagulation factor IX product Rebinyn® is now available in the US for the treatment of patients with hemophilia B.

Last May, Rebinyn was approved by the US Food and Drug Administration for on-demand treatment and control of bleeding episodes as well as perioperative management of bleeding in adults and children with hemophilia B.

The product is not approved for routine prophylaxis or immune tolerance induction in hemophilia B patients.

The full prescribing information is available at www.Rebinyn.com.

Rebinyn is also approved for use in the European Union, where it is known as nonacog beta pegol or by the brand name Refixia.

There, the product is approved for use as prophylaxis, for on-demand treatment of bleeding, and for control of bleeding related to surgical procedures in adolescents (older than 12 years of age) and adults with hemophilia B.

Trial results

The US and European approvals of nonacog beta pegol (N9-GP) were based on results from the paradigm™ clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.

Paradigm 4 was an extension trial enrolling patients who had participated in the phase 3 trials paradigm 2 and paradigm 3.

In paradigm 2, researchers assessed N9-GP as treatment and prophylaxis in previously treated patients with hemophilia B. In paradigm 3, researchers assessed N9-GP in hemophilia B patients undergoing surgical procedures.

Paradigm 4 included 71 patients (ages 13 to 70) who continued to receive N9-GP as on-demand treatment (40 IU/kg for mild/moderate bleeds and 80 IU/kg for severe bleeds) or prophylaxis (10 IU/kg or 40 IU/kg once-weekly). Sixty-five patients completed treatment.

Safety

None of the patients developed factor IX inhibitors. Two patients had transient binding antibodies to N9-GP, but there was no sign that these antibodies had an inhibitory effect.

Four patients developed anti-CHO antibodies, but only 2 of these patients were still positive for these antibodies at the end of the trial.

There were a total of 155 adverse events. However, only 4 of these (in 3 patients) were considered possibly or probably related to N9-GP.

These events consisted of an injection site rash in 1 patient, 2 overdoses in 1 patient, and neutropenia in 1 patient. The rash and neutropenia resolved, and the patient who overdosed recovered without complications.

Efficacy

The researchers said the success rate for the treatment of reported bleeds was 94.6%. Most bleeds (87.9%) were resolved with a single injection of N9-GP, but 9.2% required 2 injections, and 2.9% required 3 or 4 injections.

The median annualized bleeding rate for patients on prophylaxis was 1.05 (interquartile range [IQR], 0.00–2.20) overall. It was 1.36 (IQR, 0.00-2.23) for the 10 IU/kg arm and 1.00 (IQR, 0.00-2.03) for the 40 IU/kg arm.

There were 14 patients on prophylaxis who underwent 23 minor surgical procedures.

The hemostatic response was considered “excellent” (better than expected/predicted for the procedure in question) in 19 procedures and “good” (as expected) in 2 procedures. In the remaining 2 procedures, hemostatic responses were not determined.

Photo from Novo Nordisk

The recombinant, GlycoPEGylated coagulation factor IX product Rebinyn® is now available in the US for the treatment of patients with hemophilia B.

Last May, Rebinyn was approved by the US Food and Drug Administration for on-demand treatment and control of bleeding episodes as well as perioperative management of bleeding in adults and children with hemophilia B.

The product is not approved for routine prophylaxis or immune tolerance induction in hemophilia B patients.

The full prescribing information is available at www.Rebinyn.com.

Rebinyn is also approved for use in the European Union, where it is known as nonacog beta pegol or by the brand name Refixia.

There, the product is approved for use as prophylaxis, for on-demand treatment of bleeding, and for control of bleeding related to surgical procedures in adolescents (older than 12 years of age) and adults with hemophilia B.

Trial results

The US and European approvals of nonacog beta pegol (N9-GP) were based on results from the paradigm™ clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.

Paradigm 4 was an extension trial enrolling patients who had participated in the phase 3 trials paradigm 2 and paradigm 3.

In paradigm 2, researchers assessed N9-GP as treatment and prophylaxis in previously treated patients with hemophilia B. In paradigm 3, researchers assessed N9-GP in hemophilia B patients undergoing surgical procedures.

Paradigm 4 included 71 patients (ages 13 to 70) who continued to receive N9-GP as on-demand treatment (40 IU/kg for mild/moderate bleeds and 80 IU/kg for severe bleeds) or prophylaxis (10 IU/kg or 40 IU/kg once-weekly). Sixty-five patients completed treatment.

Safety

None of the patients developed factor IX inhibitors. Two patients had transient binding antibodies to N9-GP, but there was no sign that these antibodies had an inhibitory effect.

Four patients developed anti-CHO antibodies, but only 2 of these patients were still positive for these antibodies at the end of the trial.

There were a total of 155 adverse events. However, only 4 of these (in 3 patients) were considered possibly or probably related to N9-GP.

These events consisted of an injection site rash in 1 patient, 2 overdoses in 1 patient, and neutropenia in 1 patient. The rash and neutropenia resolved, and the patient who overdosed recovered without complications.

Efficacy

The researchers said the success rate for the treatment of reported bleeds was 94.6%. Most bleeds (87.9%) were resolved with a single injection of N9-GP, but 9.2% required 2 injections, and 2.9% required 3 or 4 injections.

The median annualized bleeding rate for patients on prophylaxis was 1.05 (interquartile range [IQR], 0.00–2.20) overall. It was 1.36 (IQR, 0.00-2.23) for the 10 IU/kg arm and 1.00 (IQR, 0.00-2.03) for the 40 IU/kg arm.

There were 14 patients on prophylaxis who underwent 23 minor surgical procedures.

The hemostatic response was considered “excellent” (better than expected/predicted for the procedure in question) in 19 procedures and “good” (as expected) in 2 procedures. In the remaining 2 procedures, hemostatic responses were not determined.

Photo by Bill Branson

Azacitidine for injection (Vidaza®) is now available in China.

The nucleoside metabolic inhibitor was approved in China to treat patients with intermediate-2/high-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) with 20% to 30% bone marrow blasts, and chronic myelomonocytic leukemia (CMML).

Azacitidine for injection is marketed in China by BeiGene Ltd. under an exclusive license from Celgene Corporation.

“Vidaza is the only approved hypomethylating agent shown to prolong survival for patients with MDS and the first new treatment for MDS patients approved in China since 2009,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene.

“We are excited to announce that the first prescription was made in January 2018. From now on, Chinese patients can benefit from Vidaza in hospitals around China.”

Azacitidine was evaluated in a global phase 3 trial of patients with intermediate-2- and high-risk MDS, CMML, or AML (AZA-001). Results from this trial were published in The Lancet Oncology in 2009.

Patients were randomized to receive azacitidine plus best supportive care (BSC, n=179) or conventional care regimens plus BSC (105 to BSC alone, 49 to low-dose cytarabine, and 25 to chemotherapy with cytarabine and anthracycline).

Azacitidine was given subcutaneously at a dose of 75 mg/m² daily for 7 consecutive days every 28 days until disease progression, relapse after response, or unacceptable toxicity.

The median overall survival was 24.5 months with azacitidine, compared to 15 months for patients treated with conventional care regimens.

There was a higher hematologic response rate in the azacitidine arm than the conventional care arm—29% and 12%, respectively.

In the azacitidine group, 45% of patients who were dependent on red blood cell transfusions at baseline became transfusion independent, compared with 11% in the conventional care group.

Forty-six percent of patients in the azacitidine arm and 63% in the conventional care arm died.

Grade 3/4 hematologic toxicity (in the azacitidine and conventional care arms, respectively) included neutropenia (91% and 76%), thrombocytopenia (85% and 80%), and anemia (57% and 68%).

Photo by Bill Branson

Azacitidine for injection (Vidaza®) is now available in China.

The nucleoside metabolic inhibitor was approved in China to treat patients with intermediate-2/high-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) with 20% to 30% bone marrow blasts, and chronic myelomonocytic leukemia (CMML).

Azacitidine for injection is marketed in China by BeiGene Ltd. under an exclusive license from Celgene Corporation.

“Vidaza is the only approved hypomethylating agent shown to prolong survival for patients with MDS and the first new treatment for MDS patients approved in China since 2009,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene.

“We are excited to announce that the first prescription was made in January 2018. From now on, Chinese patients can benefit from Vidaza in hospitals around China.”

Azacitidine was evaluated in a global phase 3 trial of patients with intermediate-2- and high-risk MDS, CMML, or AML (AZA-001). Results from this trial were published in The Lancet Oncology in 2009.

Patients were randomized to receive azacitidine plus best supportive care (BSC, n=179) or conventional care regimens plus BSC (105 to BSC alone, 49 to low-dose cytarabine, and 25 to chemotherapy with cytarabine and anthracycline).

Azacitidine was given subcutaneously at a dose of 75 mg/m² daily for 7 consecutive days every 28 days until disease progression, relapse after response, or unacceptable toxicity.

The median overall survival was 24.5 months with azacitidine, compared to 15 months for patients treated with conventional care regimens.

There was a higher hematologic response rate in the azacitidine arm than the conventional care arm—29% and 12%, respectively.

In the azacitidine group, 45% of patients who were dependent on red blood cell transfusions at baseline became transfusion independent, compared with 11% in the conventional care group.

Forty-six percent of patients in the azacitidine arm and 63% in the conventional care arm died.

Grade 3/4 hematologic toxicity (in the azacitidine and conventional care arms, respectively) included neutropenia (91% and 76%), thrombocytopenia (85% and 80%), and anemia (57% and 68%).

Photo by Bill Branson

Azacitidine for injection (Vidaza®) is now available in China.

The nucleoside metabolic inhibitor was approved in China to treat patients with intermediate-2/high-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) with 20% to 30% bone marrow blasts, and chronic myelomonocytic leukemia (CMML).

Azacitidine for injection is marketed in China by BeiGene Ltd. under an exclusive license from Celgene Corporation.

“Vidaza is the only approved hypomethylating agent shown to prolong survival for patients with MDS and the first new treatment for MDS patients approved in China since 2009,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene.

“We are excited to announce that the first prescription was made in January 2018. From now on, Chinese patients can benefit from Vidaza in hospitals around China.”

Azacitidine was evaluated in a global phase 3 trial of patients with intermediate-2- and high-risk MDS, CMML, or AML (AZA-001). Results from this trial were published in The Lancet Oncology in 2009.

Patients were randomized to receive azacitidine plus best supportive care (BSC, n=179) or conventional care regimens plus BSC (105 to BSC alone, 49 to low-dose cytarabine, and 25 to chemotherapy with cytarabine and anthracycline).

Azacitidine was given subcutaneously at a dose of 75 mg/m² daily for 7 consecutive days every 28 days until disease progression, relapse after response, or unacceptable toxicity.

The median overall survival was 24.5 months with azacitidine, compared to 15 months for patients treated with conventional care regimens.

There was a higher hematologic response rate in the azacitidine arm than the conventional care arm—29% and 12%, respectively.

In the azacitidine group, 45% of patients who were dependent on red blood cell transfusions at baseline became transfusion independent, compared with 11% in the conventional care group.

Forty-six percent of patients in the azacitidine arm and 63% in the conventional care arm died.

Grade 3/4 hematologic toxicity (in the azacitidine and conventional care arms, respectively) included neutropenia (91% and 76%), thrombocytopenia (85% and 80%), and anemia (57% and 68%).