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Selinexor on fast track for DLBCL
The U.S. Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export (SINE) compound being developed by Karyopharm Therapeutics Inc.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA says its fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs.
Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“The receipt of fast track designation from the FDA for selinexor in relapsed DLBCL underscores the great unmet medical need for this aggressive form of lymphoma,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL.”
Last month, the FDA accepted a new drug application for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
The U.S. Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export (SINE) compound being developed by Karyopharm Therapeutics Inc.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA says its fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs.
Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“The receipt of fast track designation from the FDA for selinexor in relapsed DLBCL underscores the great unmet medical need for this aggressive form of lymphoma,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL.”
Last month, the FDA accepted a new drug application for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
The U.S. Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export (SINE) compound being developed by Karyopharm Therapeutics Inc.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA says its fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs.
Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“The receipt of fast track designation from the FDA for selinexor in relapsed DLBCL underscores the great unmet medical need for this aggressive form of lymphoma,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL.”
Last month, the FDA accepted a new drug application for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
ICYMI: Elotuzumab reduces progression risk in lenalidomide-refractory multiple myeloma
Patients with multiple myeloma who did not respond to treatment with lenalidomide and a proteasome inhibitor had a significantly lower risk of progression or death when receiving elotuzumab plus pomalidomide and dexamethasone, compared with pomalidomide and dexamethasone alone (hazard ratio, 0.54; 95% confidence interval, 0.34-0.86; P = .008), according to results of a multicenter, randomized, open-label, phase 2 trial published in the New England Journal of Medicine 2018 Nov 7. doi: 10.1056/NEJMoa1805762.
Study results of ELOQUENT-3 were presented earlier this year at the Annual Congress of the European Hematology Association.
Patients with multiple myeloma who did not respond to treatment with lenalidomide and a proteasome inhibitor had a significantly lower risk of progression or death when receiving elotuzumab plus pomalidomide and dexamethasone, compared with pomalidomide and dexamethasone alone (hazard ratio, 0.54; 95% confidence interval, 0.34-0.86; P = .008), according to results of a multicenter, randomized, open-label, phase 2 trial published in the New England Journal of Medicine 2018 Nov 7. doi: 10.1056/NEJMoa1805762.
Study results of ELOQUENT-3 were presented earlier this year at the Annual Congress of the European Hematology Association.
Patients with multiple myeloma who did not respond to treatment with lenalidomide and a proteasome inhibitor had a significantly lower risk of progression or death when receiving elotuzumab plus pomalidomide and dexamethasone, compared with pomalidomide and dexamethasone alone (hazard ratio, 0.54; 95% confidence interval, 0.34-0.86; P = .008), according to results of a multicenter, randomized, open-label, phase 2 trial published in the New England Journal of Medicine 2018 Nov 7. doi: 10.1056/NEJMoa1805762.
Study results of ELOQUENT-3 were presented earlier this year at the Annual Congress of the European Hematology Association.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
FDA approves elotuzumab with pom/dex in refractory myeloma
The who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved in combination with lenalidomide and dexamethasone to treat adult myeloma patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from ELOQUENT-3. This phase 2 trial enrolled multiple myeloma patients who had refractory or relapsed disease and had received both lenalidomide and a proteasome inhibitor.
In the trial, patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n = 60) or pomalidomide and dexamethasone (Pd, n = 57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P = .0029); the rate of complete response or stringent complete response was 8.3% and 1.8%, respectively.
Median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (P = .0078).
Serious adverse events occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious adverse events were pneumonia and respiratory tract infection.
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available on the Empliciti website.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved in combination with lenalidomide and dexamethasone to treat adult myeloma patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from ELOQUENT-3. This phase 2 trial enrolled multiple myeloma patients who had refractory or relapsed disease and had received both lenalidomide and a proteasome inhibitor.
In the trial, patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n = 60) or pomalidomide and dexamethasone (Pd, n = 57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P = .0029); the rate of complete response or stringent complete response was 8.3% and 1.8%, respectively.
Median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (P = .0078).
Serious adverse events occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious adverse events were pneumonia and respiratory tract infection.
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available on the Empliciti website.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved in combination with lenalidomide and dexamethasone to treat adult myeloma patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from ELOQUENT-3. This phase 2 trial enrolled multiple myeloma patients who had refractory or relapsed disease and had received both lenalidomide and a proteasome inhibitor.
In the trial, patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n = 60) or pomalidomide and dexamethasone (Pd, n = 57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P = .0029); the rate of complete response or stringent complete response was 8.3% and 1.8%, respectively.
Median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (P = .0078).
Serious adverse events occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious adverse events were pneumonia and respiratory tract infection.
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available on the Empliciti website.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
Combo appears safe, active in rel/ref NHL
The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
Results
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
Results
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
Results
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
Sandoz won’t seek U.S. approval for rituximab biosimilar
Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimiliar of Rituxan/Mabthera.
GP2013 (Rixathon, Riximyo) is already approved outside the U.S.
Sandoz was seeking U.S. approval of GP2013 for all the same indications as the reference product—B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
The U.S. Food and Drug Administration (FDA) had accepted the biologics license application (BLA) for GP2013 in September 2017.
In May of this year, the FDA issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission for GP2013.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market. Now, the company’s position has changed.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab, but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” said Stefan Hendriks, global head of biopharmaceuticals at Sandoz.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by the ASSIST-FL trial (NCT01419665), in which researchers compared GP2013 to the reference product. Results from this trial were published in The Lancet Haematology in July 2017.
The phase 3 trial included adults with previously untreated, advanced stage follicular lymphoma. Patients received 8 cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% (271/311) in the GP2013 arm and 88% in the rituximab arm (274/313). Complete response rates were 15% (n=46) and 13% (n=42), respectively.
Rates of adverse events (AEs) were 93% in the GP2013 arm and 91% in the rituximab arm. Rates of serious AEs were 23% and 20%, respectively. The rate of discontinuation due to AEs was 7% in both arms.
The most common AE was neutropenia, which occurred in 26% of patients in the GP2013 arm and 30% of those in the rituximab arm in the combination phase. Rates of neutropenia in the maintenance phase were 10% and 6%, respectively.
Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimiliar of Rituxan/Mabthera.
GP2013 (Rixathon, Riximyo) is already approved outside the U.S.
Sandoz was seeking U.S. approval of GP2013 for all the same indications as the reference product—B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
The U.S. Food and Drug Administration (FDA) had accepted the biologics license application (BLA) for GP2013 in September 2017.
In May of this year, the FDA issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission for GP2013.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market. Now, the company’s position has changed.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab, but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” said Stefan Hendriks, global head of biopharmaceuticals at Sandoz.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by the ASSIST-FL trial (NCT01419665), in which researchers compared GP2013 to the reference product. Results from this trial were published in The Lancet Haematology in July 2017.
The phase 3 trial included adults with previously untreated, advanced stage follicular lymphoma. Patients received 8 cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% (271/311) in the GP2013 arm and 88% in the rituximab arm (274/313). Complete response rates were 15% (n=46) and 13% (n=42), respectively.
Rates of adverse events (AEs) were 93% in the GP2013 arm and 91% in the rituximab arm. Rates of serious AEs were 23% and 20%, respectively. The rate of discontinuation due to AEs was 7% in both arms.
The most common AE was neutropenia, which occurred in 26% of patients in the GP2013 arm and 30% of those in the rituximab arm in the combination phase. Rates of neutropenia in the maintenance phase were 10% and 6%, respectively.
Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimiliar of Rituxan/Mabthera.
GP2013 (Rixathon, Riximyo) is already approved outside the U.S.
Sandoz was seeking U.S. approval of GP2013 for all the same indications as the reference product—B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
The U.S. Food and Drug Administration (FDA) had accepted the biologics license application (BLA) for GP2013 in September 2017.
In May of this year, the FDA issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission for GP2013.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market. Now, the company’s position has changed.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab, but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” said Stefan Hendriks, global head of biopharmaceuticals at Sandoz.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by the ASSIST-FL trial (NCT01419665), in which researchers compared GP2013 to the reference product. Results from this trial were published in The Lancet Haematology in July 2017.
The phase 3 trial included adults with previously untreated, advanced stage follicular lymphoma. Patients received 8 cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% (271/311) in the GP2013 arm and 88% in the rituximab arm (274/313). Complete response rates were 15% (n=46) and 13% (n=42), respectively.
Rates of adverse events (AEs) were 93% in the GP2013 arm and 91% in the rituximab arm. Rates of serious AEs were 23% and 20%, respectively. The rate of discontinuation due to AEs was 7% in both arms.
The most common AE was neutropenia, which occurred in 26% of patients in the GP2013 arm and 30% of those in the rituximab arm in the combination phase. Rates of neutropenia in the maintenance phase were 10% and 6%, respectively.
Sandoz halts pursuit of U.S. approval for rituximab biosimilar
.
Sandoz, a division of Novartis, was seeking Food and Drug Administration approval of GP2013 for all the same indications as the reference product – B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
GP2013 already is approved in the European Union and elsewhere.
The FDA had accepted the biologics license application (BLA) for GP2013 in September 2017. In May 2018, the agency issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in a statement.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by results from the ASSIST-FL trial, in which researchers compared GP2013 with the reference product (Lancet Haematol. 2017 Aug;4[8]:e350-61).
The phase 3 trial included adults with previously untreated, advanced-stage follicular lymphoma. Patients received eight cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% in the GP2013 arm and 88% in the rituximab arm.
.
Sandoz, a division of Novartis, was seeking Food and Drug Administration approval of GP2013 for all the same indications as the reference product – B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
GP2013 already is approved in the European Union and elsewhere.
The FDA had accepted the biologics license application (BLA) for GP2013 in September 2017. In May 2018, the agency issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in a statement.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by results from the ASSIST-FL trial, in which researchers compared GP2013 with the reference product (Lancet Haematol. 2017 Aug;4[8]:e350-61).
The phase 3 trial included adults with previously untreated, advanced-stage follicular lymphoma. Patients received eight cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% in the GP2013 arm and 88% in the rituximab arm.
.
Sandoz, a division of Novartis, was seeking Food and Drug Administration approval of GP2013 for all the same indications as the reference product – B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
GP2013 already is approved in the European Union and elsewhere.
The FDA had accepted the biologics license application (BLA) for GP2013 in September 2017. In May 2018, the agency issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in a statement.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by results from the ASSIST-FL trial, in which researchers compared GP2013 with the reference product (Lancet Haematol. 2017 Aug;4[8]:e350-61).
The phase 3 trial included adults with previously untreated, advanced-stage follicular lymphoma. Patients received eight cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% in the GP2013 arm and 88% in the rituximab arm.
FDA and EC approve pegfilgrastim biosimilar
The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).
Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.
Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”
The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”
The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.
The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).
Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.
“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.
“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”
The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).
Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.
Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”
The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”
The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.
The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).
Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.
“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.
“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”
The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).
Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.
Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”
The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”
The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.
The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).
Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.
“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.
“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”
Haploidentical transplantation holds promise in relapsed myeloma
, investigators have reported.
The rate of non-relapse mortality at one year was 21% in the retrospective analysis of 96 patients, recently reported in the journal Biology of Blood and Marrow Transplantation.
Haploidentical allogeneic hematopoietic stem cell transplant (allo-HCT) is currently limited in use due to a high rate of relapse, but may hold potential promise for future applications, according to Firoozeh Sahebi, MD, a hematologist with the City of Hope Medical Center, Duarte, Calif., and colleagues. “Our results demonstrate that haploidentical allo-HCT can be safely performed in appropriate patients with MM who lack on HLA-matched sibling or unrelated donor.”
“The allo-HCT platform can be used in the context of other post-transplantation immune-based strategies, such as donor-derived chimeric antigen receptor T cells and natural killer cell infusions, newer immunomodulatory drugs or proteasome inhibitors, bispecific T cell engagers, and bispecific killer cell engagers, to further enhance antitumor effects and ultimately improve survival in an appropriate patient population,” Dr. Sahebi and colleagues said in their report.
The investigators reported results of a retrospective analysis including 96 patients with relapsed multiple myeloma who had failed at least one previous autologous HCT. They underwent haploidentical allo-HCT at European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers between 2008 and 2016.
Median follow-up in the analysis was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, while 75% had recovery of platelets by day 60, Dr. Sahebi and co-investigators reported.
The 1-year nonrelapse mortality rate was 21%, but the cumulative risk of relapse and progression at 2 years was 56%, according to the study results. Two-year progression-free survival was reported to be 17%, while overall survival was 48%.
Acute graft-versus-host-disease (GVHD) of grades II-IV occurred in 39% by 100 days, while chronic GVHD was seen in 46% at 2 years, the report shows.
Factors linked to improved overall survival at 2 years included use of bone marrow as the source of stem cells, and the use of cyclophosphamide after transplantation, according to Dr. Sahebi and co-authors.
By contrast, factors that had no impact on overall survival, progression-free survival, or non-relapse mortality included disease status (ie, degree of response), gender, conditioning regimen intensity, presence of cytomegalovirus in the blood, or donor-recipient sex mismatch.
This analysis was conducted in part due to the limited availability of matched donors, along with the promising results of allo-HCT in other malignancies, according to investigators.
There were no conflicts of interest to report related to this research, Dr. Sahebi and colleagues reported in the journal.
SOURCE: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.
, investigators have reported.
The rate of non-relapse mortality at one year was 21% in the retrospective analysis of 96 patients, recently reported in the journal Biology of Blood and Marrow Transplantation.
Haploidentical allogeneic hematopoietic stem cell transplant (allo-HCT) is currently limited in use due to a high rate of relapse, but may hold potential promise for future applications, according to Firoozeh Sahebi, MD, a hematologist with the City of Hope Medical Center, Duarte, Calif., and colleagues. “Our results demonstrate that haploidentical allo-HCT can be safely performed in appropriate patients with MM who lack on HLA-matched sibling or unrelated donor.”
“The allo-HCT platform can be used in the context of other post-transplantation immune-based strategies, such as donor-derived chimeric antigen receptor T cells and natural killer cell infusions, newer immunomodulatory drugs or proteasome inhibitors, bispecific T cell engagers, and bispecific killer cell engagers, to further enhance antitumor effects and ultimately improve survival in an appropriate patient population,” Dr. Sahebi and colleagues said in their report.
The investigators reported results of a retrospective analysis including 96 patients with relapsed multiple myeloma who had failed at least one previous autologous HCT. They underwent haploidentical allo-HCT at European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers between 2008 and 2016.
Median follow-up in the analysis was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, while 75% had recovery of platelets by day 60, Dr. Sahebi and co-investigators reported.
The 1-year nonrelapse mortality rate was 21%, but the cumulative risk of relapse and progression at 2 years was 56%, according to the study results. Two-year progression-free survival was reported to be 17%, while overall survival was 48%.
Acute graft-versus-host-disease (GVHD) of grades II-IV occurred in 39% by 100 days, while chronic GVHD was seen in 46% at 2 years, the report shows.
Factors linked to improved overall survival at 2 years included use of bone marrow as the source of stem cells, and the use of cyclophosphamide after transplantation, according to Dr. Sahebi and co-authors.
By contrast, factors that had no impact on overall survival, progression-free survival, or non-relapse mortality included disease status (ie, degree of response), gender, conditioning regimen intensity, presence of cytomegalovirus in the blood, or donor-recipient sex mismatch.
This analysis was conducted in part due to the limited availability of matched donors, along with the promising results of allo-HCT in other malignancies, according to investigators.
There were no conflicts of interest to report related to this research, Dr. Sahebi and colleagues reported in the journal.
SOURCE: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.
, investigators have reported.
The rate of non-relapse mortality at one year was 21% in the retrospective analysis of 96 patients, recently reported in the journal Biology of Blood and Marrow Transplantation.
Haploidentical allogeneic hematopoietic stem cell transplant (allo-HCT) is currently limited in use due to a high rate of relapse, but may hold potential promise for future applications, according to Firoozeh Sahebi, MD, a hematologist with the City of Hope Medical Center, Duarte, Calif., and colleagues. “Our results demonstrate that haploidentical allo-HCT can be safely performed in appropriate patients with MM who lack on HLA-matched sibling or unrelated donor.”
“The allo-HCT platform can be used in the context of other post-transplantation immune-based strategies, such as donor-derived chimeric antigen receptor T cells and natural killer cell infusions, newer immunomodulatory drugs or proteasome inhibitors, bispecific T cell engagers, and bispecific killer cell engagers, to further enhance antitumor effects and ultimately improve survival in an appropriate patient population,” Dr. Sahebi and colleagues said in their report.
The investigators reported results of a retrospective analysis including 96 patients with relapsed multiple myeloma who had failed at least one previous autologous HCT. They underwent haploidentical allo-HCT at European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers between 2008 and 2016.
Median follow-up in the analysis was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, while 75% had recovery of platelets by day 60, Dr. Sahebi and co-investigators reported.
The 1-year nonrelapse mortality rate was 21%, but the cumulative risk of relapse and progression at 2 years was 56%, according to the study results. Two-year progression-free survival was reported to be 17%, while overall survival was 48%.
Acute graft-versus-host-disease (GVHD) of grades II-IV occurred in 39% by 100 days, while chronic GVHD was seen in 46% at 2 years, the report shows.
Factors linked to improved overall survival at 2 years included use of bone marrow as the source of stem cells, and the use of cyclophosphamide after transplantation, according to Dr. Sahebi and co-authors.
By contrast, factors that had no impact on overall survival, progression-free survival, or non-relapse mortality included disease status (ie, degree of response), gender, conditioning regimen intensity, presence of cytomegalovirus in the blood, or donor-recipient sex mismatch.
This analysis was conducted in part due to the limited availability of matched donors, along with the promising results of allo-HCT in other malignancies, according to investigators.
There were no conflicts of interest to report related to this research, Dr. Sahebi and colleagues reported in the journal.
SOURCE: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.
FROM BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Key clinical point: Haploidentical allogeneic transplantation is feasible and had an acceptable rate of non-relapse mortality, setting the stage for its use in future combination strategies.
Major finding: The cumulative risk of relapse and progression at 2 years was 56%, and the 1-year nonrelapse mortality was 21%.
Study details: A retrospective analysis including 96 patients who underwent haploidentical allogeneic hematopoietic stem cell transplantation between 2008 and 2016.
Disclosures: Authors reported no conflicts of interest.
Source: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.
Health Canada approves pralatrexate for rel/ref PTCL
Health Canada has granted conditional approval for pralatrexate (Folotyn®) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Pralatrexate received a Notice of Compliance with Conditions (NOC/c), which is an approval granted on the basis of promising evidence of clinical effectiveness that must be verified in additional clinical trials.
To be approved under Health Canada’s NOC/c policy, a product must be intended for the treatment, prevention, or diagnosis of a serious, life-threatening, or severely debilitating illness.
In addition, the product must have demonstrated promising benefit, be of high quality, have an acceptable safety profile based on a benefit/risk assessment, and either respond to a serious unmet need or provide a significant improvement over existing therapies.
The NOC/c for pralatrexate is based on response rates in the single-arm, phase 2 PROPEL trial. Results from PROPEL were published in the Journal of Clinical Oncology in 2011.
The trial enrolled 115 patients with relapsed or refractory PTCL who had received a median of three (range, 1-12) prior systemic therapies.
The patients received pralatrexate once weekly at a dose of 30 mg/m2 for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity.
In the 109 evaluable patients, the response rate was 29% (32/109). The complete response rate was 11% (n=12), and the partial response rate was 18% (n=20).
The median duration of response was 10.1 months, the median progression-free survival was 3.5 months, and the median overall survival was 14.5 months.
The most common adverse events (AEs) were mucositis (71%), thrombocytopenia (41%), nausea (41%), fatigue (36%), pyrexia (34%), anemia (34%), constipation (34%), edema (31%), cough (29%), epistaxis (26%), vomiting (25%), neutropenia (25%), and diarrhea (23%).
The most common grade 3/4 AEs were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%).
The product monograph for pralatrexate contains a boxed warning highlighting the risk of AEs associated with pralatrexate use, including dermatologic reactions, bone marrow suppression, infection, mucosal inflammation, tumor lysis syndrome, potential fetal harm, and pulmonary toxicity.
The product monograph is available for download from the website of Servier Canada, the company marketing pralatrexate in Canada.
Health Canada has granted conditional approval for pralatrexate (Folotyn®) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Pralatrexate received a Notice of Compliance with Conditions (NOC/c), which is an approval granted on the basis of promising evidence of clinical effectiveness that must be verified in additional clinical trials.
To be approved under Health Canada’s NOC/c policy, a product must be intended for the treatment, prevention, or diagnosis of a serious, life-threatening, or severely debilitating illness.
In addition, the product must have demonstrated promising benefit, be of high quality, have an acceptable safety profile based on a benefit/risk assessment, and either respond to a serious unmet need or provide a significant improvement over existing therapies.
The NOC/c for pralatrexate is based on response rates in the single-arm, phase 2 PROPEL trial. Results from PROPEL were published in the Journal of Clinical Oncology in 2011.
The trial enrolled 115 patients with relapsed or refractory PTCL who had received a median of three (range, 1-12) prior systemic therapies.
The patients received pralatrexate once weekly at a dose of 30 mg/m2 for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity.
In the 109 evaluable patients, the response rate was 29% (32/109). The complete response rate was 11% (n=12), and the partial response rate was 18% (n=20).
The median duration of response was 10.1 months, the median progression-free survival was 3.5 months, and the median overall survival was 14.5 months.
The most common adverse events (AEs) were mucositis (71%), thrombocytopenia (41%), nausea (41%), fatigue (36%), pyrexia (34%), anemia (34%), constipation (34%), edema (31%), cough (29%), epistaxis (26%), vomiting (25%), neutropenia (25%), and diarrhea (23%).
The most common grade 3/4 AEs were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%).
The product monograph for pralatrexate contains a boxed warning highlighting the risk of AEs associated with pralatrexate use, including dermatologic reactions, bone marrow suppression, infection, mucosal inflammation, tumor lysis syndrome, potential fetal harm, and pulmonary toxicity.
The product monograph is available for download from the website of Servier Canada, the company marketing pralatrexate in Canada.
Health Canada has granted conditional approval for pralatrexate (Folotyn®) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Pralatrexate received a Notice of Compliance with Conditions (NOC/c), which is an approval granted on the basis of promising evidence of clinical effectiveness that must be verified in additional clinical trials.
To be approved under Health Canada’s NOC/c policy, a product must be intended for the treatment, prevention, or diagnosis of a serious, life-threatening, or severely debilitating illness.
In addition, the product must have demonstrated promising benefit, be of high quality, have an acceptable safety profile based on a benefit/risk assessment, and either respond to a serious unmet need or provide a significant improvement over existing therapies.
The NOC/c for pralatrexate is based on response rates in the single-arm, phase 2 PROPEL trial. Results from PROPEL were published in the Journal of Clinical Oncology in 2011.
The trial enrolled 115 patients with relapsed or refractory PTCL who had received a median of three (range, 1-12) prior systemic therapies.
The patients received pralatrexate once weekly at a dose of 30 mg/m2 for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity.
In the 109 evaluable patients, the response rate was 29% (32/109). The complete response rate was 11% (n=12), and the partial response rate was 18% (n=20).
The median duration of response was 10.1 months, the median progression-free survival was 3.5 months, and the median overall survival was 14.5 months.
The most common adverse events (AEs) were mucositis (71%), thrombocytopenia (41%), nausea (41%), fatigue (36%), pyrexia (34%), anemia (34%), constipation (34%), edema (31%), cough (29%), epistaxis (26%), vomiting (25%), neutropenia (25%), and diarrhea (23%).
The most common grade 3/4 AEs were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%).
The product monograph for pralatrexate contains a boxed warning highlighting the risk of AEs associated with pralatrexate use, including dermatologic reactions, bone marrow suppression, infection, mucosal inflammation, tumor lysis syndrome, potential fetal harm, and pulmonary toxicity.
The product monograph is available for download from the website of Servier Canada, the company marketing pralatrexate in Canada.
EC approves venetoclax in combo with rituximab
The European Commission (EC) has approved a new indication for venetoclax (Venclyxto®).
The drug is now approved for use in combination with rituximab to treat patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
The approval is valid in all member states of the European Union as well as Iceland, Liechtenstein, and Norway.
The EC’s approval is based on results from the phase 3 MURANO trial, which were published in The New England Journal of Medicine in March.
The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.
According to an independent review committee, the overall response rate was 92.3% in the VEN+R arm and 72.3% in the B+R arm. The investigator-assessed overall response rates were 93.3% and 67.7%, respectively.
According to investigators, the median progression-free survival (PFS) was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio [HR]=0.17; P<0.0001).
According to the independent review committee, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (HR=0.20; P<0.0001).
Investigators said the 2-year PFS rate was 84.9% in the VEN+R arm and 36.3% in the B+R arm.
They said the 2-year overall survival rates were 91.9% and 86.6%, respectively (HR=0.48; P<0.0001). The median overall survival was not reached in either arm.
Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment arms (in the VEN+R and B+R arms, respectively) included:
- Neutropenia (57.7% and 38.8%)
- Infections and infestations (17.5% and 21.8%)
- Anemia (10.8% and 13.8%)
- Thrombocytopenia (5.7% and 10.1%)
- Febrile neutropenia (3.6% and 9.6%)
- Pneumonia (5.2% and 8.0%)
- Infusion-related reactions (1.5% and 5.3%)
- Tumor lysis syndrome (3.1% and 1.1%)
- Hypotension (0% and 2.7%)
- Hyperglycemia (2.1% and 0%)
- Hypogammaglobulinemia (2.1% and 0%).
Serious AEs with at least a 2% difference in incidence between the arms (in the VEN+R and B+R arms, respectively) were:
- Pneumonia (8.2% and 8.0%)
- Febrile neutropenia (3.6% and 8.5%)
- Pyrexia (2.6% and 6.9%)
- Anemia (1.5% and 2.7%)
- Infusion-related reactions (0.5% and 3.2%)
- Sepsis (0.5% and 2.1%)
- Tumor lysis syndrome (2.1% and 0.5%)
- Hypotension (0% and 2.7%).
Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.
Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter’s transformation.
The European Commission (EC) has approved a new indication for venetoclax (Venclyxto®).
The drug is now approved for use in combination with rituximab to treat patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
The approval is valid in all member states of the European Union as well as Iceland, Liechtenstein, and Norway.
The EC’s approval is based on results from the phase 3 MURANO trial, which were published in The New England Journal of Medicine in March.
The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.
According to an independent review committee, the overall response rate was 92.3% in the VEN+R arm and 72.3% in the B+R arm. The investigator-assessed overall response rates were 93.3% and 67.7%, respectively.
According to investigators, the median progression-free survival (PFS) was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio [HR]=0.17; P<0.0001).
According to the independent review committee, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (HR=0.20; P<0.0001).
Investigators said the 2-year PFS rate was 84.9% in the VEN+R arm and 36.3% in the B+R arm.
They said the 2-year overall survival rates were 91.9% and 86.6%, respectively (HR=0.48; P<0.0001). The median overall survival was not reached in either arm.
Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment arms (in the VEN+R and B+R arms, respectively) included:
- Neutropenia (57.7% and 38.8%)
- Infections and infestations (17.5% and 21.8%)
- Anemia (10.8% and 13.8%)
- Thrombocytopenia (5.7% and 10.1%)
- Febrile neutropenia (3.6% and 9.6%)
- Pneumonia (5.2% and 8.0%)
- Infusion-related reactions (1.5% and 5.3%)
- Tumor lysis syndrome (3.1% and 1.1%)
- Hypotension (0% and 2.7%)
- Hyperglycemia (2.1% and 0%)
- Hypogammaglobulinemia (2.1% and 0%).
Serious AEs with at least a 2% difference in incidence between the arms (in the VEN+R and B+R arms, respectively) were:
- Pneumonia (8.2% and 8.0%)
- Febrile neutropenia (3.6% and 8.5%)
- Pyrexia (2.6% and 6.9%)
- Anemia (1.5% and 2.7%)
- Infusion-related reactions (0.5% and 3.2%)
- Sepsis (0.5% and 2.1%)
- Tumor lysis syndrome (2.1% and 0.5%)
- Hypotension (0% and 2.7%).
Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.
Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter’s transformation.
The European Commission (EC) has approved a new indication for venetoclax (Venclyxto®).
The drug is now approved for use in combination with rituximab to treat patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
The approval is valid in all member states of the European Union as well as Iceland, Liechtenstein, and Norway.
The EC’s approval is based on results from the phase 3 MURANO trial, which were published in The New England Journal of Medicine in March.
The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.
According to an independent review committee, the overall response rate was 92.3% in the VEN+R arm and 72.3% in the B+R arm. The investigator-assessed overall response rates were 93.3% and 67.7%, respectively.
According to investigators, the median progression-free survival (PFS) was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio [HR]=0.17; P<0.0001).
According to the independent review committee, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (HR=0.20; P<0.0001).
Investigators said the 2-year PFS rate was 84.9% in the VEN+R arm and 36.3% in the B+R arm.
They said the 2-year overall survival rates were 91.9% and 86.6%, respectively (HR=0.48; P<0.0001). The median overall survival was not reached in either arm.
Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment arms (in the VEN+R and B+R arms, respectively) included:
- Neutropenia (57.7% and 38.8%)
- Infections and infestations (17.5% and 21.8%)
- Anemia (10.8% and 13.8%)
- Thrombocytopenia (5.7% and 10.1%)
- Febrile neutropenia (3.6% and 9.6%)
- Pneumonia (5.2% and 8.0%)
- Infusion-related reactions (1.5% and 5.3%)
- Tumor lysis syndrome (3.1% and 1.1%)
- Hypotension (0% and 2.7%)
- Hyperglycemia (2.1% and 0%)
- Hypogammaglobulinemia (2.1% and 0%).
Serious AEs with at least a 2% difference in incidence between the arms (in the VEN+R and B+R arms, respectively) were:
- Pneumonia (8.2% and 8.0%)
- Febrile neutropenia (3.6% and 8.5%)
- Pyrexia (2.6% and 6.9%)
- Anemia (1.5% and 2.7%)
- Infusion-related reactions (0.5% and 3.2%)
- Sepsis (0.5% and 2.1%)
- Tumor lysis syndrome (2.1% and 0.5%)
- Hypotension (0% and 2.7%).
Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.
Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter’s transformation.