This article is more than 5 years old. Information may no longer be current.
FDA approves Zydelig for CLL, SLL, follicular lymphoma
Click Here to Manage Email Alerts
The FDA today approved the PI3 kinase delta inhibitor idelalisib as monotherapy for patients with follicular B-cell non-Hodgkin’s lymphoma and small lymphocytic lymphoma, and also as part of combination therapy with rituximab for patients with high-risk relapsed or refractory chronic lymphocytic leukemia.
The FDA granted traditional approval to idelalisib (Zydelig, Gilead) for the treatment of relapsed/refractory CLL.
Richard Pazdur
“In less than a year, we have seen considerable progress in the availability of treatments for chronic lymphocytic leukemia,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “Zydelig’s approval to treat CLL reflects the promise of the breakthrough therapy designation program and represents the FDA’s commitment to working cooperatively with companies to expedite a drug’s development, review and approval.”
The approval was based in part on results from the phase 3 Study 116 trial, designed to evaluate the safety and effectiveness of idelalisib in 220 patients with relapsed/refractory CLL. Researchers randomly assigned patients to rituximab (Rituxan; Genentech, Biogen Idec) plus idelalisib or rituximab plus placebo.
Study 116 was stopped early in October 2013 by an independent Data Monitoring Committee after results suggested a statistically significant benefit in PFS in the idelalisib arm (HR=0.18; 955 CI, 0.1-0.32). Results from a second interim analysis continued to show a statistically significant improvement with the addition of idelalisib to rituximab.
The approval for relapsed follicular lymphoma and relapsed small lymphocytic leukemia (SLL) fell under FDA’s accelerated approval program.
The safety and efficacy of idelalisib for those indications were assessed in the Study 101-09 trial, which included 123 patients with indolent non-Hodgkin lymphomas. All patients were treated with idelalisib and were evaluated for objective response rate.
Study results indicated objective response rates of 54% among patients with relapsed follicular lymphoma and 58% among patients with SLL.
Bruce D. Cheson
“Zydelig is a much-needed new treatment option for appropriate patients with CLL and these indolent lymphomas who have experienced relapses and have limited, if any, treatment options,” Bruce D. Cheson, MD, director of hematology research at Georgetown Lombardi Comprehensive Cancer Center and a principal investigator on the phase 3 trial that evaluated idelalisib in CLL, said in a press release. “In clinical studies among patients with relapsed CLL, follicular lymphoma and SLL, Zydelig produced strong responses, including a significant improvement in progression-free survival in CLL. I believe it helps fill a significant unmet need for these patients.”
Idelalisib carries a Boxed Warning alerting patients and health care professionals about the potential for fatal and serious toxicities, including liver toxicity, diarrhea and colitis, pneumonitis and intestinal perforation.
In addition, idelalisib is approved with a Risk Evaluation and Mitigation Strategy comprised of a communication plan to ensure health care providers who are likely to prescribe idelalisib are fully informed about these risks.
The most frequent adverse events observed during clinical trials of idelalisib included diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills and rash. Common laboratory abnormalities included neutropenia, hypertriglyceridemia, hyperglycemia and elevated levels of liver enzymes.
Perspective
Back to Top
Jennifer R. Brown, MD, PhD
Idelalisib is a highly effective drug for CLL [and it] adds substantially to our available therapies. What we don’t know is how best to integrate the use of ibrutinib (Imbruvica; Pharmacyclics, Janssen) and idelalisib — for example, with respect to sequencing or combinations — for maximum benefit for any given patient. The next few years should provide much greater insights into this question.Click Here to Manage Email Alerts