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The oral kinase inhibitor idelalisib has been approved for treating patients with relapsed chronic lymphocytic leukemia, follicular lymphoma, and small lymphocytic lymphoma, with a boxed warning about fatal and serious toxicities associated with treatment, the Food and Drug Administration announced on July 23.
The three approved indications for idelalisib – administered at a recommended starting dose of 150 mg, twice a day – are for:
• Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other comorbidities. This is a traditional approval based on progression-free survival (PFS) data.
• Relapsed follicular B-cell non-Hodgkin’s lymphoma (FL) in patients who have received at least two prior systemic therapies.
• Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.
The FL and SLL indications, based on objective response rates in one study, are accelerated approvals, which provides patients with serious or life-threatening diseases earlier access to a promising drug based on an effect on a surrogate endpoint considered " reasonably likely to predict clinical benefit," according to the FDA. Full approval is contingent on the manufacturer conducting trials confirming clinical benefits; if they do not, the FDA can withdraw the approval.
Idelalisib is being marketed as Zydelig, by Gilead Sciences. There is also a Risk Evaluation and Mitigation Strategy (REMS) in place for the drug, which includes a communication plan to ensure that prescribers are fully informed about treatment-associated risks. The boxed warning lists the risks of fatal and/or serious hepatoxicity (affecting 14% of treated patients); fatal and/or serious and severe diarrhea or colitis (also affecting 14% of treated patients); as well as fatal and serious pneumonitis; and fatal and serious intestinal perforation.
Idelalisib is an oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, "a protein that plays a role in the activation, proliferation, and viability of B cells," according to a Gilead statement announcing the approval, which added that PI3K delta signaling "is active in many B-cell leukemias and lymphomas, and by inhibiting the protein, Zydelig blocks several cellular signaling pathways that drive B-cell viability."
The FDA granted a full approval for the CLL indication, based on a phase III study of 220 patients, which was stopped early in October 2013 at the first-specified interim analysis. Median PFS was not reached among those randomized to on idelalisib plus rituximab, but was at least 10.7 months, and was 5.5 months among those randomized to placebo plus rituximab (N. Engl. J. Med. 2014;370:997-1007). "Results from a second interim analysis continued to show a statistically significant improvement for Zydelig and Rituxan over placebo and Rituxan," the FDA statement said.
The accelerated approvals for relapsed FL and relapsed SLL were based on a single-arm phase II study of 123 patients refractory to rituximab and chemotherapy including alkylating agents, treated with idelalisib. The objective response rates were 54% among those with relapsed FL, and 58% of those with SLL in the study (N. Engl. J. Med. 2014;370:1008-18).
Common adverse events associated with treatment included diarrhea, fever, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash; and common lab abnormalities associated with treatment included neutropenia, hypertriglyceridemia, hyperglycemia, and liver enzyme elevations, according to the FDA.
In the FDA statement, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, pointed out that in less than a year, "We have seen considerable progress in the availability of treatments for chronic lymphocytic leukemia." The other treatments for CLL are obinutuzumab (Gazyva), approved in November 2013; ibrutinib (Imbruvica), approved in February 2014; and ofatumumab (Arzerra) approved in April 2014.
Prescribing information is available at the FDA website.
The oral kinase inhibitor idelalisib has been approved for treating patients with relapsed chronic lymphocytic leukemia, follicular lymphoma, and small lymphocytic lymphoma, with a boxed warning about fatal and serious toxicities associated with treatment, the Food and Drug Administration announced on July 23.
The three approved indications for idelalisib – administered at a recommended starting dose of 150 mg, twice a day – are for:
• Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other comorbidities. This is a traditional approval based on progression-free survival (PFS) data.
• Relapsed follicular B-cell non-Hodgkin’s lymphoma (FL) in patients who have received at least two prior systemic therapies.
• Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.
The FL and SLL indications, based on objective response rates in one study, are accelerated approvals, which provides patients with serious or life-threatening diseases earlier access to a promising drug based on an effect on a surrogate endpoint considered " reasonably likely to predict clinical benefit," according to the FDA. Full approval is contingent on the manufacturer conducting trials confirming clinical benefits; if they do not, the FDA can withdraw the approval.
Idelalisib is being marketed as Zydelig, by Gilead Sciences. There is also a Risk Evaluation and Mitigation Strategy (REMS) in place for the drug, which includes a communication plan to ensure that prescribers are fully informed about treatment-associated risks. The boxed warning lists the risks of fatal and/or serious hepatoxicity (affecting 14% of treated patients); fatal and/or serious and severe diarrhea or colitis (also affecting 14% of treated patients); as well as fatal and serious pneumonitis; and fatal and serious intestinal perforation.
Idelalisib is an oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, "a protein that plays a role in the activation, proliferation, and viability of B cells," according to a Gilead statement announcing the approval, which added that PI3K delta signaling "is active in many B-cell leukemias and lymphomas, and by inhibiting the protein, Zydelig blocks several cellular signaling pathways that drive B-cell viability."
The FDA granted a full approval for the CLL indication, based on a phase III study of 220 patients, which was stopped early in October 2013 at the first-specified interim analysis. Median PFS was not reached among those randomized to on idelalisib plus rituximab, but was at least 10.7 months, and was 5.5 months among those randomized to placebo plus rituximab (N. Engl. J. Med. 2014;370:997-1007). "Results from a second interim analysis continued to show a statistically significant improvement for Zydelig and Rituxan over placebo and Rituxan," the FDA statement said.
The accelerated approvals for relapsed FL and relapsed SLL were based on a single-arm phase II study of 123 patients refractory to rituximab and chemotherapy including alkylating agents, treated with idelalisib. The objective response rates were 54% among those with relapsed FL, and 58% of those with SLL in the study (N. Engl. J. Med. 2014;370:1008-18).
Common adverse events associated with treatment included diarrhea, fever, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash; and common lab abnormalities associated with treatment included neutropenia, hypertriglyceridemia, hyperglycemia, and liver enzyme elevations, according to the FDA.
In the FDA statement, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, pointed out that in less than a year, "We have seen considerable progress in the availability of treatments for chronic lymphocytic leukemia." The other treatments for CLL are obinutuzumab (Gazyva), approved in November 2013; ibrutinib (Imbruvica), approved in February 2014; and ofatumumab (Arzerra) approved in April 2014.
Prescribing information is available at the FDA website.
The oral kinase inhibitor idelalisib has been approved for treating patients with relapsed chronic lymphocytic leukemia, follicular lymphoma, and small lymphocytic lymphoma, with a boxed warning about fatal and serious toxicities associated with treatment, the Food and Drug Administration announced on July 23.
The three approved indications for idelalisib – administered at a recommended starting dose of 150 mg, twice a day – are for:
• Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other comorbidities. This is a traditional approval based on progression-free survival (PFS) data.
• Relapsed follicular B-cell non-Hodgkin’s lymphoma (FL) in patients who have received at least two prior systemic therapies.
• Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.
The FL and SLL indications, based on objective response rates in one study, are accelerated approvals, which provides patients with serious or life-threatening diseases earlier access to a promising drug based on an effect on a surrogate endpoint considered " reasonably likely to predict clinical benefit," according to the FDA. Full approval is contingent on the manufacturer conducting trials confirming clinical benefits; if they do not, the FDA can withdraw the approval.
Idelalisib is being marketed as Zydelig, by Gilead Sciences. There is also a Risk Evaluation and Mitigation Strategy (REMS) in place for the drug, which includes a communication plan to ensure that prescribers are fully informed about treatment-associated risks. The boxed warning lists the risks of fatal and/or serious hepatoxicity (affecting 14% of treated patients); fatal and/or serious and severe diarrhea or colitis (also affecting 14% of treated patients); as well as fatal and serious pneumonitis; and fatal and serious intestinal perforation.
Idelalisib is an oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, "a protein that plays a role in the activation, proliferation, and viability of B cells," according to a Gilead statement announcing the approval, which added that PI3K delta signaling "is active in many B-cell leukemias and lymphomas, and by inhibiting the protein, Zydelig blocks several cellular signaling pathways that drive B-cell viability."
The FDA granted a full approval for the CLL indication, based on a phase III study of 220 patients, which was stopped early in October 2013 at the first-specified interim analysis. Median PFS was not reached among those randomized to on idelalisib plus rituximab, but was at least 10.7 months, and was 5.5 months among those randomized to placebo plus rituximab (N. Engl. J. Med. 2014;370:997-1007). "Results from a second interim analysis continued to show a statistically significant improvement for Zydelig and Rituxan over placebo and Rituxan," the FDA statement said.
The accelerated approvals for relapsed FL and relapsed SLL were based on a single-arm phase II study of 123 patients refractory to rituximab and chemotherapy including alkylating agents, treated with idelalisib. The objective response rates were 54% among those with relapsed FL, and 58% of those with SLL in the study (N. Engl. J. Med. 2014;370:1008-18).
Common adverse events associated with treatment included diarrhea, fever, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash; and common lab abnormalities associated with treatment included neutropenia, hypertriglyceridemia, hyperglycemia, and liver enzyme elevations, according to the FDA.
In the FDA statement, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, pointed out that in less than a year, "We have seen considerable progress in the availability of treatments for chronic lymphocytic leukemia." The other treatments for CLL are obinutuzumab (Gazyva), approved in November 2013; ibrutinib (Imbruvica), approved in February 2014; and ofatumumab (Arzerra) approved in April 2014.
Prescribing information is available at the FDA website.
