HT Staff

Photo courtesy of Janssen

Health Canada has approved a third indication for daratumumab (Darzalex®) in multiple myeloma (MM).

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

Health Canada previously approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least one prior therapy.

Health Canada also approved daratumumab as monotherapy for MM patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent.

For the product monograph and more information about daratumumab, visit https://www.janssen.com/canada/products.

Trial results

Health Canada’s latest approval of daratumumab is supported by data from the phase 3 ALCYONE study (NCT02195479), which were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

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

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

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

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

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

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

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

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

The ALCYONE trial was sponsored by Janssen Research & Development, LLC.

Photo courtesy of Janssen

Health Canada has approved a third indication for daratumumab (Darzalex®) in multiple myeloma (MM).

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

Health Canada previously approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least one prior therapy.

Health Canada also approved daratumumab as monotherapy for MM patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent.

For the product monograph and more information about daratumumab, visit https://www.janssen.com/canada/products.

Trial results

Health Canada’s latest approval of daratumumab is supported by data from the phase 3 ALCYONE study (NCT02195479), which were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

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

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

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

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

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

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

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

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

The ALCYONE trial was sponsored by Janssen Research & Development, LLC.

Photo courtesy of Janssen

Health Canada has approved a third indication for daratumumab (Darzalex®) in multiple myeloma (MM).

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

Health Canada previously approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least one prior therapy.

Health Canada also approved daratumumab as monotherapy for MM patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent.

For the product monograph and more information about daratumumab, visit https://www.janssen.com/canada/products.

Trial results

Health Canada’s latest approval of daratumumab is supported by data from the phase 3 ALCYONE study (NCT02195479), which were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

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

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

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

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

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

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

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

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

The ALCYONE trial was sponsored by Janssen Research & Development, LLC.

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for brentuximab vedotin (BV).

The CHMP has recommended approval for BV (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) to treat adults with previously untreated, CD30+, stage IV Hodgkin lymphoma (HL).

The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of a CHMP recommendation.

BV is already EC-approved to treat adults with:

• CD30+ HL at increased risk of relapse or progression following autologous stem cell transplant (ASCT)
• Relapsed or refractory, CD30+ HL following ASCT or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Relapsed or refractory systemic anaplastic large-cell lymphoma
• CD30+ cutaneous T-cell lymphoma after at least one prior systemic therapy.

Phase 3 trial

The CHMP’s recommendation to approve BV in combination with AVD is supported by the phase 3 ECHELON-1 trial (NCT01712490).

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

In this trial, researchers compared BV plus AVD (BV+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

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 committee, BV+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 BV+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 BV+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 BV+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 BV+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 BV+AVD, while pulmonary toxicity was more common with ABVD.

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals, Inc. (a Takeda company) in collaboration with Seattle Genetics, Inc.

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for brentuximab vedotin (BV).

The CHMP has recommended approval for BV (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) to treat adults with previously untreated, CD30+, stage IV Hodgkin lymphoma (HL).

The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of a CHMP recommendation.

BV is already EC-approved to treat adults with:

• CD30+ HL at increased risk of relapse or progression following autologous stem cell transplant (ASCT)
• Relapsed or refractory, CD30+ HL following ASCT or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Relapsed or refractory systemic anaplastic large-cell lymphoma
• CD30+ cutaneous T-cell lymphoma after at least one prior systemic therapy.

Phase 3 trial

The CHMP’s recommendation to approve BV in combination with AVD is supported by the phase 3 ECHELON-1 trial (NCT01712490).

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

In this trial, researchers compared BV plus AVD (BV+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

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 committee, BV+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 BV+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 BV+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 BV+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 BV+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 BV+AVD, while pulmonary toxicity was more common with ABVD.

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals, Inc. (a Takeda company) in collaboration with Seattle Genetics, Inc.

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for brentuximab vedotin (BV).

The CHMP has recommended approval for BV (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) to treat adults with previously untreated, CD30+, stage IV Hodgkin lymphoma (HL).

The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of a CHMP recommendation.

BV is already EC-approved to treat adults with:

• CD30+ HL at increased risk of relapse or progression following autologous stem cell transplant (ASCT)
• Relapsed or refractory, CD30+ HL following ASCT or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Relapsed or refractory systemic anaplastic large-cell lymphoma
• CD30+ cutaneous T-cell lymphoma after at least one prior systemic therapy.

Phase 3 trial

The CHMP’s recommendation to approve BV in combination with AVD is supported by the phase 3 ECHELON-1 trial (NCT01712490).

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

In this trial, researchers compared BV plus AVD (BV+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

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 committee, BV+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 BV+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 BV+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 BV+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 BV+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 BV+AVD, while pulmonary toxicity was more common with ABVD.

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals, Inc. (a Takeda company) in collaboration with Seattle Genetics, Inc.

Photo by Bill Branson

The thrombopoietin receptor agonist romiplostim (NPlate®) is now approved by the U.S. Food and Drug Administration (FDA) to treat pediatric patients 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim was originally FDA-approved in 2008 to treat adult patients with chronic ITP who had an insufficient response to the same treatments.

Romiplostim is manufactured by Amgen, Inc.

The FDA based its approval on two double-blind, placebo-controlled clinical trials.

NCT01444417

The phase 3 study (NCT01444417) enrolled 62 pediatric patients 1 year and older who had ITP for at least 6 months. They were refractory to or relapsed after at least one prior therapy.

Investigators randomized them 2:1 to receive romiplostim (n=42) or placebo (n=20).

The starting dose was 1 μg/kg weekly for all ages. The dose was titrated up over a 24-week period to a maximum of 10 μg/kg weekly.

Patients were a median age of 9.5 years (range, 3–17), and 57% were female. A little over half (58%) had baseline platelet counts of 20 x 10⁹/L or less, which was similar in both treatment arms.

Eighty-one percent of romiplostim-treated patients had at least two prior ITP therapies, compared with 70% in the placebo group. One patient in each group had undergone splenectomy.

Twenty-two (52%) of the romiplostim-treated patients had durable platelet responses of 50 x 10⁹/L or greater for at least six weekly assessments during weeks 18 through 25 of treatment. Two (10%) patients in the placebo arm achieved durable platelet responses.

Thirty (71%) romiplostim-treated patients achieved an overall platelet response, defined as a durable or transient platelet response. This compared with four (20%) patients in the placebo group.

Romiplostim-treated patients had platelet counts of at least 50 x 10⁹/L for a median of 12 weeks, compared to 1 week for patients in the placebo arm.

All response endpoints were significant at P<0.05.

NCT00515203

The phase 1/2 study (NCT00515203) enrolled 22 patients who had ITP for at least 6 months prior to study enrollment and were relapsed from or refractory to prior treatment.

Investigators randomized the patients 3:1 to romiplostim (n=17) or placebo (n=5).

Patients were a median age of 10 years (range, 1–17), and 27.3% were female.

Approximately 82% of patients had baseline platelet counts of 20 x 10⁹/L or less, which was similar between the treatment arms.

Eighty-eight percent of patients in the romiplostim arm had at least two prior ITP therapies, as did 100% in the placebo group.

Six patients in the romiplostim group and two in the placebo group had undergone splenectomy.

Of the 17 patients treated with romiplostim, 15 (88.2%) achieved a platelet count of 50 x 10⁹/L or great for 2 consecutive weeks.

The same 15 patients also achieved an increase in platelet count of 20 x 10⁹/L or greater above baseline for 2 consecutive weeks during the treatment period.

None of the placebo-treated patients achieved either endpoint.

The adverse events profile in pediatric patients was compiled from the two trials and reflects a median drug exposure of 168 days for 59 patients.

The most common adverse events, occurring in 25% or more of romiplostim-treated patients, were contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%). These occurred with an incidence at least 5% higher than in the placebo group.

Dosing

The recommended starting dose for pediatric patients is 1 µg/kg based on actual body weight and administered as a weekly subcutaneous injection.

The dose should be adjusted in increments of 1 µg/kg until the patient achieves a platelet count of 50 x 10⁹/L or greater.

The prescribing information recommends reassessing patients’ body weight every 12 weeks. 

Photo by Bill Branson

The thrombopoietin receptor agonist romiplostim (NPlate®) is now approved by the U.S. Food and Drug Administration (FDA) to treat pediatric patients 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim was originally FDA-approved in 2008 to treat adult patients with chronic ITP who had an insufficient response to the same treatments.

Romiplostim is manufactured by Amgen, Inc.

The FDA based its approval on two double-blind, placebo-controlled clinical trials.

NCT01444417

The phase 3 study (NCT01444417) enrolled 62 pediatric patients 1 year and older who had ITP for at least 6 months. They were refractory to or relapsed after at least one prior therapy.

Investigators randomized them 2:1 to receive romiplostim (n=42) or placebo (n=20).

The starting dose was 1 μg/kg weekly for all ages. The dose was titrated up over a 24-week period to a maximum of 10 μg/kg weekly.

Patients were a median age of 9.5 years (range, 3–17), and 57% were female. A little over half (58%) had baseline platelet counts of 20 x 10⁹/L or less, which was similar in both treatment arms.

Eighty-one percent of romiplostim-treated patients had at least two prior ITP therapies, compared with 70% in the placebo group. One patient in each group had undergone splenectomy.

Twenty-two (52%) of the romiplostim-treated patients had durable platelet responses of 50 x 10⁹/L or greater for at least six weekly assessments during weeks 18 through 25 of treatment. Two (10%) patients in the placebo arm achieved durable platelet responses.

Thirty (71%) romiplostim-treated patients achieved an overall platelet response, defined as a durable or transient platelet response. This compared with four (20%) patients in the placebo group.

Romiplostim-treated patients had platelet counts of at least 50 x 10⁹/L for a median of 12 weeks, compared to 1 week for patients in the placebo arm.

All response endpoints were significant at P<0.05.

NCT00515203

The phase 1/2 study (NCT00515203) enrolled 22 patients who had ITP for at least 6 months prior to study enrollment and were relapsed from or refractory to prior treatment.

Investigators randomized the patients 3:1 to romiplostim (n=17) or placebo (n=5).

Patients were a median age of 10 years (range, 1–17), and 27.3% were female.

Approximately 82% of patients had baseline platelet counts of 20 x 10⁹/L or less, which was similar between the treatment arms.

Eighty-eight percent of patients in the romiplostim arm had at least two prior ITP therapies, as did 100% in the placebo group.

Six patients in the romiplostim group and two in the placebo group had undergone splenectomy.

Of the 17 patients treated with romiplostim, 15 (88.2%) achieved a platelet count of 50 x 10⁹/L or great for 2 consecutive weeks.

The same 15 patients also achieved an increase in platelet count of 20 x 10⁹/L or greater above baseline for 2 consecutive weeks during the treatment period.

None of the placebo-treated patients achieved either endpoint.

The adverse events profile in pediatric patients was compiled from the two trials and reflects a median drug exposure of 168 days for 59 patients.

The most common adverse events, occurring in 25% or more of romiplostim-treated patients, were contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%). These occurred with an incidence at least 5% higher than in the placebo group.

Dosing

The recommended starting dose for pediatric patients is 1 µg/kg based on actual body weight and administered as a weekly subcutaneous injection.

The dose should be adjusted in increments of 1 µg/kg until the patient achieves a platelet count of 50 x 10⁹/L or greater.

The prescribing information recommends reassessing patients’ body weight every 12 weeks. 

Photo by Bill Branson

The thrombopoietin receptor agonist romiplostim (NPlate®) is now approved by the U.S. Food and Drug Administration (FDA) to treat pediatric patients 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim was originally FDA-approved in 2008 to treat adult patients with chronic ITP who had an insufficient response to the same treatments.

Romiplostim is manufactured by Amgen, Inc.

The FDA based its approval on two double-blind, placebo-controlled clinical trials.

NCT01444417

The phase 3 study (NCT01444417) enrolled 62 pediatric patients 1 year and older who had ITP for at least 6 months. They were refractory to or relapsed after at least one prior therapy.

Investigators randomized them 2:1 to receive romiplostim (n=42) or placebo (n=20).

The starting dose was 1 μg/kg weekly for all ages. The dose was titrated up over a 24-week period to a maximum of 10 μg/kg weekly.

Patients were a median age of 9.5 years (range, 3–17), and 57% were female. A little over half (58%) had baseline platelet counts of 20 x 10⁹/L or less, which was similar in both treatment arms.

Eighty-one percent of romiplostim-treated patients had at least two prior ITP therapies, compared with 70% in the placebo group. One patient in each group had undergone splenectomy.

Twenty-two (52%) of the romiplostim-treated patients had durable platelet responses of 50 x 10⁹/L or greater for at least six weekly assessments during weeks 18 through 25 of treatment. Two (10%) patients in the placebo arm achieved durable platelet responses.

Thirty (71%) romiplostim-treated patients achieved an overall platelet response, defined as a durable or transient platelet response. This compared with four (20%) patients in the placebo group.

Romiplostim-treated patients had platelet counts of at least 50 x 10⁹/L for a median of 12 weeks, compared to 1 week for patients in the placebo arm.

All response endpoints were significant at P<0.05.

NCT00515203

The phase 1/2 study (NCT00515203) enrolled 22 patients who had ITP for at least 6 months prior to study enrollment and were relapsed from or refractory to prior treatment.

Investigators randomized the patients 3:1 to romiplostim (n=17) or placebo (n=5).

Patients were a median age of 10 years (range, 1–17), and 27.3% were female.

Approximately 82% of patients had baseline platelet counts of 20 x 10⁹/L or less, which was similar between the treatment arms.

Eighty-eight percent of patients in the romiplostim arm had at least two prior ITP therapies, as did 100% in the placebo group.

Six patients in the romiplostim group and two in the placebo group had undergone splenectomy.

Of the 17 patients treated with romiplostim, 15 (88.2%) achieved a platelet count of 50 x 10⁹/L or great for 2 consecutive weeks.

The same 15 patients also achieved an increase in platelet count of 20 x 10⁹/L or greater above baseline for 2 consecutive weeks during the treatment period.

None of the placebo-treated patients achieved either endpoint.

The adverse events profile in pediatric patients was compiled from the two trials and reflects a median drug exposure of 168 days for 59 patients.

The most common adverse events, occurring in 25% or more of romiplostim-treated patients, were contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%). These occurred with an incidence at least 5% higher than in the placebo group.

Dosing

The recommended starting dose for pediatric patients is 1 µg/kg based on actual body weight and administered as a weekly subcutaneous injection.

The dose should be adjusted in increments of 1 µg/kg until the patient achieves a platelet count of 50 x 10⁹/L or greater.

The prescribing information recommends reassessing patients’ body weight every 12 weeks. 

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has released a safety communication warning that cases of  differentiation syndrome are going unnoticed in patients treated with the IDH2 inhibitor enasidenib (Idhifa).

Enasidenib is FDA-approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation.

The drug is known to be associated with differentiation syndrome, and the prescribing information contains a boxed warning about this life-threatening condition.

However, the FDA has found that patients and healthcare providers are missing the signs and symptoms of differentiation syndrome, and some patients are not receiving the necessary treatment in time.

The FDA is also warning that differentiation syndrome has been observed in AML patients taking the IDH1 inhibitor ivosidenib (Tibsovo).

However, the agency has not provided many details on cases related to this drug, which is FDA-approved to treat adults with relapsed or refractory AML who have an IDH1 mutation.

Recognizing differentiation syndrome

The FDA says differentiation syndrome may occur anywhere from 10 days to 5 months after starting enasidenib.

The agency is advising healthcare providers to describe the symptoms of differentiation syndrome to patients, both when starting them on enasidenib and at follow-up visits.

Symptoms of differentiation syndrome include:

• Acute respiratory distress represented by dyspnea and/or hypoxia and a need for supplemental oxygen
• Pulmonary infiltrates and pleural effusion
• Fever
• Lymphadenopathy
• Bone pain
• Peripheral edema with rapid weight gain
• Pericardial effusion
• Hepatic, renal, and multiorgan dysfunction.

The FDA notes that differentiation syndrome may be mistaken for cardiogenic pulmonary edema, pneumonia, or sepsis.

Treatment

If healthcare providers suspect differentiation syndrome, they should promptly administer oral or intravenous corticosteroids, such as dexamethasone at 10 mg every 12 hours, according to the FDA.

Providers should also monitor hemodynamics until improvement and provide supportive care as necessary.

If patients continue to experience renal dysfunction or severe pulmonary symptoms requiring intubation or ventilator support for more than 48 hours after starting corticosteroids, enasidenib should be stopped until signs and symptoms of differentiation syndrome are no longer severe.

Corticosteroids should be tapered only after the symptoms resolve completely, as differentiation syndrome may recur if treatment is stopped too soon.

Cases of differentiation syndrome

The FDA notes that, in the phase 1/2 trial that supported the U.S. approval of enasidenib, at least 14% of patients experienced differentiation syndrome.

The manufacturer’s latest safety report includes 5 deaths (from May 1, 2018, to July 31, 2018) associated with differentiation syndrome in patients taking enasidenib.

Differentiation syndrome was listed as the only cause of death in two cases. In the remaining three cases, patients also had hemorrhagic stroke, pneumonia and sepsis, and sepsis alone.

One patient received systemic corticosteroids promptly but may have died of sepsis during hospitalization. In another patient, differentiation syndrome was not diagnosed or treated promptly. Treatment details are not available for the remaining three patients, according to the FDA.

The FDA has also performed a systematic analysis of differentiation syndrome in 293 patients treated with enasidenib (n=214) or ivosidenib (n=179).

With both drugs, the incidence of differentiation syndrome was 19%. The condition was fatal in 6% (n=2) of ivosidenib-treated patients and 5% (n=2) of enasidenib-treated patients.

Additional results from this analysis are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 288).

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has released a safety communication warning that cases of  differentiation syndrome are going unnoticed in patients treated with the IDH2 inhibitor enasidenib (Idhifa).

Enasidenib is FDA-approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation.

The drug is known to be associated with differentiation syndrome, and the prescribing information contains a boxed warning about this life-threatening condition.

However, the FDA has found that patients and healthcare providers are missing the signs and symptoms of differentiation syndrome, and some patients are not receiving the necessary treatment in time.

The FDA is also warning that differentiation syndrome has been observed in AML patients taking the IDH1 inhibitor ivosidenib (Tibsovo).

However, the agency has not provided many details on cases related to this drug, which is FDA-approved to treat adults with relapsed or refractory AML who have an IDH1 mutation.

Recognizing differentiation syndrome

The FDA says differentiation syndrome may occur anywhere from 10 days to 5 months after starting enasidenib.

The agency is advising healthcare providers to describe the symptoms of differentiation syndrome to patients, both when starting them on enasidenib and at follow-up visits.

Symptoms of differentiation syndrome include:

• Acute respiratory distress represented by dyspnea and/or hypoxia and a need for supplemental oxygen
• Pulmonary infiltrates and pleural effusion
• Fever
• Lymphadenopathy
• Bone pain
• Peripheral edema with rapid weight gain
• Pericardial effusion
• Hepatic, renal, and multiorgan dysfunction.

The FDA notes that differentiation syndrome may be mistaken for cardiogenic pulmonary edema, pneumonia, or sepsis.

Treatment

If healthcare providers suspect differentiation syndrome, they should promptly administer oral or intravenous corticosteroids, such as dexamethasone at 10 mg every 12 hours, according to the FDA.

Providers should also monitor hemodynamics until improvement and provide supportive care as necessary.

If patients continue to experience renal dysfunction or severe pulmonary symptoms requiring intubation or ventilator support for more than 48 hours after starting corticosteroids, enasidenib should be stopped until signs and symptoms of differentiation syndrome are no longer severe.

Corticosteroids should be tapered only after the symptoms resolve completely, as differentiation syndrome may recur if treatment is stopped too soon.

Cases of differentiation syndrome

The FDA notes that, in the phase 1/2 trial that supported the U.S. approval of enasidenib, at least 14% of patients experienced differentiation syndrome.

The manufacturer’s latest safety report includes 5 deaths (from May 1, 2018, to July 31, 2018) associated with differentiation syndrome in patients taking enasidenib.

Differentiation syndrome was listed as the only cause of death in two cases. In the remaining three cases, patients also had hemorrhagic stroke, pneumonia and sepsis, and sepsis alone.

One patient received systemic corticosteroids promptly but may have died of sepsis during hospitalization. In another patient, differentiation syndrome was not diagnosed or treated promptly. Treatment details are not available for the remaining three patients, according to the FDA.

The FDA has also performed a systematic analysis of differentiation syndrome in 293 patients treated with enasidenib (n=214) or ivosidenib (n=179).

With both drugs, the incidence of differentiation syndrome was 19%. The condition was fatal in 6% (n=2) of ivosidenib-treated patients and 5% (n=2) of enasidenib-treated patients.

Additional results from this analysis are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 288).

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has released a safety communication warning that cases of  differentiation syndrome are going unnoticed in patients treated with the IDH2 inhibitor enasidenib (Idhifa).

Enasidenib is FDA-approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation.

The drug is known to be associated with differentiation syndrome, and the prescribing information contains a boxed warning about this life-threatening condition.

However, the FDA has found that patients and healthcare providers are missing the signs and symptoms of differentiation syndrome, and some patients are not receiving the necessary treatment in time.

The FDA is also warning that differentiation syndrome has been observed in AML patients taking the IDH1 inhibitor ivosidenib (Tibsovo).

However, the agency has not provided many details on cases related to this drug, which is FDA-approved to treat adults with relapsed or refractory AML who have an IDH1 mutation.

Recognizing differentiation syndrome

The FDA says differentiation syndrome may occur anywhere from 10 days to 5 months after starting enasidenib.

The agency is advising healthcare providers to describe the symptoms of differentiation syndrome to patients, both when starting them on enasidenib and at follow-up visits.

Symptoms of differentiation syndrome include:

• Acute respiratory distress represented by dyspnea and/or hypoxia and a need for supplemental oxygen
• Pulmonary infiltrates and pleural effusion
• Fever
• Lymphadenopathy
• Bone pain
• Peripheral edema with rapid weight gain
• Pericardial effusion
• Hepatic, renal, and multiorgan dysfunction.

The FDA notes that differentiation syndrome may be mistaken for cardiogenic pulmonary edema, pneumonia, or sepsis.

Treatment

If healthcare providers suspect differentiation syndrome, they should promptly administer oral or intravenous corticosteroids, such as dexamethasone at 10 mg every 12 hours, according to the FDA.

Providers should also monitor hemodynamics until improvement and provide supportive care as necessary.

If patients continue to experience renal dysfunction or severe pulmonary symptoms requiring intubation or ventilator support for more than 48 hours after starting corticosteroids, enasidenib should be stopped until signs and symptoms of differentiation syndrome are no longer severe.

Corticosteroids should be tapered only after the symptoms resolve completely, as differentiation syndrome may recur if treatment is stopped too soon.

Cases of differentiation syndrome

The FDA notes that, in the phase 1/2 trial that supported the U.S. approval of enasidenib, at least 14% of patients experienced differentiation syndrome.

The manufacturer’s latest safety report includes 5 deaths (from May 1, 2018, to July 31, 2018) associated with differentiation syndrome in patients taking enasidenib.

Differentiation syndrome was listed as the only cause of death in two cases. In the remaining three cases, patients also had hemorrhagic stroke, pneumonia and sepsis, and sepsis alone.

One patient received systemic corticosteroids promptly but may have died of sepsis during hospitalization. In another patient, differentiation syndrome was not diagnosed or treated promptly. Treatment details are not available for the remaining three patients, according to the FDA.

The FDA has also performed a systematic analysis of differentiation syndrome in 293 patients treated with enasidenib (n=214) or ivosidenib (n=179).

With both drugs, the incidence of differentiation syndrome was 19%. The condition was fatal in 6% (n=2) of ivosidenib-treated patients and 5% (n=2) of enasidenib-treated patients.

Additional results from this analysis are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 288).

Astellas Pharma

The U.S. Food and Drug Administration (FDA) has approved gilteritinib (Xospata) for use in adults who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, as detected by an FDA-approved test.

The FDA also expanded the approved indication for the LeukoStrat CDx FLT3 Mutation Assay to include use with gilteritinib.

The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect FLT3 mutations in patients with AML.

Gilteritinib, developed by Astellas Pharma, has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain.

The FDA’s approval of gilteritinib was based on an interim analysis of the ADMIRAL trial (NCT02421939).

The trial enrolled adults with relapsed or refractory AML who had a FLT3 ITD, D835, or I836 mutation, according to the LeukoStrat CDx FLT3 Mutation Assay.

Patients received gilteritinib at 120 mg daily until they developed unacceptable toxicity or did not show a clinical benefit.

Efficacy results are available for 138 patients, with a median follow-up of 4.6 months (range, 2.8 to 15.8).

The complete response (CR) rate was 11.6% (16/138), the rate of CR with partial hematologic recovery (CRh) was 9.4% (13/138), and the rate of CR/CRh was 21% (29/138).

The median duration of CR/CRh was 4.6 months.

There were 106 patients who were transfusion-dependent at baseline, and 33 of these patients (31.1%) became transfusion-independent during the post-baseline period.

Seventeen of the 32 patients (53.1%) who were transfusion-independent at baseline remained transfusion-independent.

Safety results are available for 292 patients. The median duration of exposure to gilteritinib in this group was 3 months (range, 0.1 to 42.8).

The most common adverse events were myalgia/arthralgia (42%), transaminase increase (41%), fatigue/malaise (40%), fever (35%), noninfectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), constipation (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%), and vomiting (20%).

Eight percent of patients (n=22) discontinued gilteritinib due to adverse events. The most common were pneumonia (2%), sepsis (2%), and dyspnea (1%).

For more details on the ADMIRAL trial and gilteritinib, see the full prescribing information.

Astellas Pharma

The U.S. Food and Drug Administration (FDA) has approved gilteritinib (Xospata) for use in adults who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, as detected by an FDA-approved test.

The FDA also expanded the approved indication for the LeukoStrat CDx FLT3 Mutation Assay to include use with gilteritinib.

The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect FLT3 mutations in patients with AML.

Gilteritinib, developed by Astellas Pharma, has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain.

The FDA’s approval of gilteritinib was based on an interim analysis of the ADMIRAL trial (NCT02421939).

The trial enrolled adults with relapsed or refractory AML who had a FLT3 ITD, D835, or I836 mutation, according to the LeukoStrat CDx FLT3 Mutation Assay.

Patients received gilteritinib at 120 mg daily until they developed unacceptable toxicity or did not show a clinical benefit.

Efficacy results are available for 138 patients, with a median follow-up of 4.6 months (range, 2.8 to 15.8).

The complete response (CR) rate was 11.6% (16/138), the rate of CR with partial hematologic recovery (CRh) was 9.4% (13/138), and the rate of CR/CRh was 21% (29/138).

The median duration of CR/CRh was 4.6 months.

There were 106 patients who were transfusion-dependent at baseline, and 33 of these patients (31.1%) became transfusion-independent during the post-baseline period.

Seventeen of the 32 patients (53.1%) who were transfusion-independent at baseline remained transfusion-independent.

Safety results are available for 292 patients. The median duration of exposure to gilteritinib in this group was 3 months (range, 0.1 to 42.8).

The most common adverse events were myalgia/arthralgia (42%), transaminase increase (41%), fatigue/malaise (40%), fever (35%), noninfectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), constipation (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%), and vomiting (20%).

Eight percent of patients (n=22) discontinued gilteritinib due to adverse events. The most common were pneumonia (2%), sepsis (2%), and dyspnea (1%).

For more details on the ADMIRAL trial and gilteritinib, see the full prescribing information.

Astellas Pharma

The U.S. Food and Drug Administration (FDA) has approved gilteritinib (Xospata) for use in adults who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, as detected by an FDA-approved test.

The FDA also expanded the approved indication for the LeukoStrat CDx FLT3 Mutation Assay to include use with gilteritinib.

The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect FLT3 mutations in patients with AML.

Gilteritinib, developed by Astellas Pharma, has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain.

The FDA’s approval of gilteritinib was based on an interim analysis of the ADMIRAL trial (NCT02421939).

The trial enrolled adults with relapsed or refractory AML who had a FLT3 ITD, D835, or I836 mutation, according to the LeukoStrat CDx FLT3 Mutation Assay.

Patients received gilteritinib at 120 mg daily until they developed unacceptable toxicity or did not show a clinical benefit.

Efficacy results are available for 138 patients, with a median follow-up of 4.6 months (range, 2.8 to 15.8).

The complete response (CR) rate was 11.6% (16/138), the rate of CR with partial hematologic recovery (CRh) was 9.4% (13/138), and the rate of CR/CRh was 21% (29/138).

The median duration of CR/CRh was 4.6 months.

There were 106 patients who were transfusion-dependent at baseline, and 33 of these patients (31.1%) became transfusion-independent during the post-baseline period.

Seventeen of the 32 patients (53.1%) who were transfusion-independent at baseline remained transfusion-independent.

Safety results are available for 292 patients. The median duration of exposure to gilteritinib in this group was 3 months (range, 0.1 to 42.8).

The most common adverse events were myalgia/arthralgia (42%), transaminase increase (41%), fatigue/malaise (40%), fever (35%), noninfectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), constipation (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%), and vomiting (20%).

Eight percent of patients (n=22) discontinued gilteritinib due to adverse events. The most common were pneumonia (2%), sepsis (2%), and dyspnea (1%).

For more details on the ADMIRAL trial and gilteritinib, see the full prescribing information.

Photo by Bill Branson

The U.S. Food and Drug Administration (FDA) has approved a biosimilar rituximab product for the treatment of non-Hodgkin lymphoma (NHL).

Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan and the first biosimilar approved in the United States to treat NHL.

Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

Specifically, Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL.

Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.

Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy.

And Truxima is approved as a single agent to treat non-progressing, low-grade, CD20­-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.

The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.

The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”

A phase 3 trial recently published in The Lancet Haematology suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma.

For more details on Truxima, see the prescribing information.

Photo by Bill Branson

The U.S. Food and Drug Administration (FDA) has approved a biosimilar rituximab product for the treatment of non-Hodgkin lymphoma (NHL).

Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan and the first biosimilar approved in the United States to treat NHL.

Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

Specifically, Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL.

Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.

Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy.

And Truxima is approved as a single agent to treat non-progressing, low-grade, CD20­-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.

The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.

The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”

A phase 3 trial recently published in The Lancet Haematology suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma.

For more details on Truxima, see the prescribing information.

Photo by Bill Branson

The U.S. Food and Drug Administration (FDA) has approved a biosimilar rituximab product for the treatment of non-Hodgkin lymphoma (NHL).

Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan and the first biosimilar approved in the United States to treat NHL.

Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

Specifically, Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL.

Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.

Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy.

And Truxima is approved as a single agent to treat non-progressing, low-grade, CD20­-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.

The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.

The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”

A phase 3 trial recently published in The Lancet Haematology suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma.

For more details on Truxima, see the prescribing information.

Photo from Bayer

The European Commission (EC) has approved damoctocog alfa pegol (Jivi®), a recombinant human factor VIII therapy.

Damoctocog alfa pegol (formerly BAY94-9027) is approved for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older who have hemophilia A.

The approval is valid in the European Union, Norway, Iceland, and Liechtenstein.

The EC’s decision to approve damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial.

Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.

Study design

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.

In part B, researchers evaluated damoctocog alfa pegol for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received damoctocog alfa pegol for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

Efficacy

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were “moderate,” and 3.3% were “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A.

Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

The European Commission (EC) has approved damoctocog alfa pegol (Jivi®), a recombinant human factor VIII therapy.

Damoctocog alfa pegol (formerly BAY94-9027) is approved for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older who have hemophilia A.

The approval is valid in the European Union, Norway, Iceland, and Liechtenstein.

The EC’s decision to approve damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial.

Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.

Study design

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.

In part B, researchers evaluated damoctocog alfa pegol for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received damoctocog alfa pegol for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

Efficacy

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were “moderate,” and 3.3% were “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A.

Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

The European Commission (EC) has approved damoctocog alfa pegol (Jivi®), a recombinant human factor VIII therapy.

Damoctocog alfa pegol (formerly BAY94-9027) is approved for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older who have hemophilia A.

The approval is valid in the European Union, Norway, Iceland, and Liechtenstein.

The EC’s decision to approve damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial.

Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.

Study design

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.

In part B, researchers evaluated damoctocog alfa pegol for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received damoctocog alfa pegol for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

Efficacy

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were “moderate,” and 3.3% were “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A.

Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

mycosis fungoides

The European Commission (EC) has granted marketing authorization for mogamulizumab (Poteligeo), a humanized monoclonal antibody directed against CCR4.

This means mogamulizumab is approved for use in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

This approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.

Kyowa Kirin plans to launch mogamulizumab in various European markets starting next year.

The EC’s decision to approve mogamulizumab was supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.

MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.

Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to an independent review committee, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in overall response rate (ORR) with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

mycosis fungoides

The European Commission (EC) has granted marketing authorization for mogamulizumab (Poteligeo), a humanized monoclonal antibody directed against CCR4.

This means mogamulizumab is approved for use in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

This approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.

Kyowa Kirin plans to launch mogamulizumab in various European markets starting next year.

The EC’s decision to approve mogamulizumab was supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.

MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.

Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to an independent review committee, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in overall response rate (ORR) with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

mycosis fungoides

The European Commission (EC) has granted marketing authorization for mogamulizumab (Poteligeo), a humanized monoclonal antibody directed against CCR4.

This means mogamulizumab is approved for use in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

This approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.

Kyowa Kirin plans to launch mogamulizumab in various European markets starting next year.

The EC’s decision to approve mogamulizumab was supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.

MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.

Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to an independent review committee, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in overall response rate (ORR) with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

Photo courtesy of Baxalta

Health Canada has extended the approved indication for Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.

The product is now approved for use in hemophilia A patients under the age of 12 for the control and prevention of bleeding episodes, as prophylaxis to prevent or reduce the frequency of bleeding, and for perioperative management of bleeding.

Adynovate (formerly BAX 855) was first approved in Canada in November 2016. At that time, it was authorized for use in hemophilia A patients age 12 and older as on-demand treatment, as prophylaxis, and for perioperative management.

Adynovate is built on the full-length Advate molecule, but Adynovate leverages pegylation technology designed to extend the amount of FVIII available for use in the body.

The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.

Health Canada’s decision to expand the indication for Adynovate is supported by results from a phase 3 trial of pediatric patients as well as a phase 3 trial of patients undergoing surgery.

Pediatric trial

The pediatric trial enrolled 73 patients, ages 1 to 11, with previously treated hemophilia A.

Sixty-six patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.

The median annualized bleeding rate was 2.0 for all bleeds and 0 for both joint and spontaneous bleeds.

Thirty-eight percent of patients did not have any bleeding episodes, 67% had no spontaneous bleeds, and 73% had no joint bleeds.

One patient developed inhibitors, but there were no other treatment-related adverse events.

Results from this trial were published in Haemophilia in November 2016 and are available in the Canadian product monograph for Adynovate.

Perioperative study

The perioperative study included 15 patients, ages 19 to 52, with severe hemophilia A who were undergoing surgical procedures (11 of them major and four minor).

The patients received Adynovate at varying doses and schedules, depending on each patient’s pharmacokinetic profile for major procedures or Adynovate incremental recovery for minor procedures.

Intraoperative and perioperative hemostatic efficacy of Adynovate was deemed “excellent” for all 15 patients. The “excellent” rating meant that blood loss was less than or equal to that expected for the type of procedure performed in a non-hemophilic population.

Postoperatively (day 1 after the procedure), hemostatic efficacy was rated “good” for one procedure and “excellent” for the rest. The “good” rating meant that postoperative blood loss was up to 50% more than expected for the type of procedure performed in a non-hemophilic population.

There were no treatment-related adverse events or signs of immunogenicity in this trial.

Results were published in Haemophilia in June 2016 and are available in the Canadian product monograph for Adynovate.

Photo courtesy of Baxalta

Health Canada has extended the approved indication for Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.

The product is now approved for use in hemophilia A patients under the age of 12 for the control and prevention of bleeding episodes, as prophylaxis to prevent or reduce the frequency of bleeding, and for perioperative management of bleeding.

Adynovate (formerly BAX 855) was first approved in Canada in November 2016. At that time, it was authorized for use in hemophilia A patients age 12 and older as on-demand treatment, as prophylaxis, and for perioperative management.

Adynovate is built on the full-length Advate molecule, but Adynovate leverages pegylation technology designed to extend the amount of FVIII available for use in the body.

The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.

Health Canada’s decision to expand the indication for Adynovate is supported by results from a phase 3 trial of pediatric patients as well as a phase 3 trial of patients undergoing surgery.

Pediatric trial

The pediatric trial enrolled 73 patients, ages 1 to 11, with previously treated hemophilia A.

Sixty-six patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.

The median annualized bleeding rate was 2.0 for all bleeds and 0 for both joint and spontaneous bleeds.

Thirty-eight percent of patients did not have any bleeding episodes, 67% had no spontaneous bleeds, and 73% had no joint bleeds.

One patient developed inhibitors, but there were no other treatment-related adverse events.

Results from this trial were published in Haemophilia in November 2016 and are available in the Canadian product monograph for Adynovate.

Perioperative study

The perioperative study included 15 patients, ages 19 to 52, with severe hemophilia A who were undergoing surgical procedures (11 of them major and four minor).

The patients received Adynovate at varying doses and schedules, depending on each patient’s pharmacokinetic profile for major procedures or Adynovate incremental recovery for minor procedures.

Intraoperative and perioperative hemostatic efficacy of Adynovate was deemed “excellent” for all 15 patients. The “excellent” rating meant that blood loss was less than or equal to that expected for the type of procedure performed in a non-hemophilic population.

Postoperatively (day 1 after the procedure), hemostatic efficacy was rated “good” for one procedure and “excellent” for the rest. The “good” rating meant that postoperative blood loss was up to 50% more than expected for the type of procedure performed in a non-hemophilic population.

There were no treatment-related adverse events or signs of immunogenicity in this trial.

Results were published in Haemophilia in June 2016 and are available in the Canadian product monograph for Adynovate.

Photo courtesy of Baxalta

Health Canada has extended the approved indication for Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.

The product is now approved for use in hemophilia A patients under the age of 12 for the control and prevention of bleeding episodes, as prophylaxis to prevent or reduce the frequency of bleeding, and for perioperative management of bleeding.

Adynovate (formerly BAX 855) was first approved in Canada in November 2016. At that time, it was authorized for use in hemophilia A patients age 12 and older as on-demand treatment, as prophylaxis, and for perioperative management.

Adynovate is built on the full-length Advate molecule, but Adynovate leverages pegylation technology designed to extend the amount of FVIII available for use in the body.

The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.

Health Canada’s decision to expand the indication for Adynovate is supported by results from a phase 3 trial of pediatric patients as well as a phase 3 trial of patients undergoing surgery.

Pediatric trial

The pediatric trial enrolled 73 patients, ages 1 to 11, with previously treated hemophilia A.

Sixty-six patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.

The median annualized bleeding rate was 2.0 for all bleeds and 0 for both joint and spontaneous bleeds.

Thirty-eight percent of patients did not have any bleeding episodes, 67% had no spontaneous bleeds, and 73% had no joint bleeds.

One patient developed inhibitors, but there were no other treatment-related adverse events.

Results from this trial were published in Haemophilia in November 2016 and are available in the Canadian product monograph for Adynovate.

Perioperative study

The perioperative study included 15 patients, ages 19 to 52, with severe hemophilia A who were undergoing surgical procedures (11 of them major and four minor).

The patients received Adynovate at varying doses and schedules, depending on each patient’s pharmacokinetic profile for major procedures or Adynovate incremental recovery for minor procedures.

Intraoperative and perioperative hemostatic efficacy of Adynovate was deemed “excellent” for all 15 patients. The “excellent” rating meant that blood loss was less than or equal to that expected for the type of procedure performed in a non-hemophilic population.

Postoperatively (day 1 after the procedure), hemostatic efficacy was rated “good” for one procedure and “excellent” for the rest. The “good” rating meant that postoperative blood loss was up to 50% more than expected for the type of procedure performed in a non-hemophilic population.

There were no treatment-related adverse events or signs of immunogenicity in this trial.

Results were published in Haemophilia in June 2016 and are available in the Canadian product monograph for Adynovate.

Photo by Rhoda Baer

The European Commission (EC) has granted marketing authorization for Sandoz’s pegfilgrastim product Ziextenzo®, a biosimilar of Amgen’s Neulasta.

Ziextenzo is approved for the same use as the reference medicine—to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies except chronic myeloid leukemia and myelodysplastic syndromes.

The approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.

The EC’s approval was based on research suggesting Ziextenzo is comparable to Neulasta in terms of safety, efficacy, pharmacokinetics, and pharmacodynamics.^1,2,3,4

1. Blackwell K. et al. Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Ann Oncol 28, 2272-2277 (2017).

2. Nakov R. et al. Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects. 2017 San Antonio Breast Cancer Symposium, abstract P3-14-10.

3. Blackwell K. et al. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial. Oncologist 21, 789-794 (2016).

4. Harbeck N. et al. Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncol 12, 1359-1367 (2016).

Photo by Rhoda Baer

The European Commission (EC) has granted marketing authorization for Sandoz’s pegfilgrastim product Ziextenzo®, a biosimilar of Amgen’s Neulasta.

Ziextenzo is approved for the same use as the reference medicine—to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies except chronic myeloid leukemia and myelodysplastic syndromes.

The approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.

The EC’s approval was based on research suggesting Ziextenzo is comparable to Neulasta in terms of safety, efficacy, pharmacokinetics, and pharmacodynamics.^1,2,3,4

1. Blackwell K. et al. Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Ann Oncol 28, 2272-2277 (2017).

2. Nakov R. et al. Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects. 2017 San Antonio Breast Cancer Symposium, abstract P3-14-10.

3. Blackwell K. et al. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial. Oncologist 21, 789-794 (2016).

4. Harbeck N. et al. Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncol 12, 1359-1367 (2016).

Photo by Rhoda Baer

The European Commission (EC) has granted marketing authorization for Sandoz’s pegfilgrastim product Ziextenzo®, a biosimilar of Amgen’s Neulasta.

Ziextenzo is approved for the same use as the reference medicine—to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies except chronic myeloid leukemia and myelodysplastic syndromes.

The approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.

The EC’s approval was based on research suggesting Ziextenzo is comparable to Neulasta in terms of safety, efficacy, pharmacokinetics, and pharmacodynamics.^1,2,3,4

1. Blackwell K. et al. Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Ann Oncol 28, 2272-2277 (2017).

2. Nakov R. et al. Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects. 2017 San Antonio Breast Cancer Symposium, abstract P3-14-10.

3. Blackwell K. et al. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial. Oncologist 21, 789-794 (2016).

4. Harbeck N. et al. Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncol 12, 1359-1367 (2016).