The FDA approved idelalisib (Zydelig) yesterday for the treatment of relapsed chronic lymphocytic leukemia (CLL), follicular B-cell non-Hodgkin lymphoma (FL), and small lymphocytic lymphoma (SLL).
The US Food and Drug Administration (FDA) approved idelalisib (Zydelig) for the treatment of relapsed chronic lymphocytic leukemia (CLL), follicular B-cell non-Hodgkin lymphoma (FL), and small lymphocytic lymphoma (SLL), another type of non-Hodgkin lymphoma.
The approval for CLL is in combination with rituximab (Rituxan) for patients deemed eligible for rituximab monotherapy based on their comorbidities and performance status. Idelalisib had received breakthrough designation from the FDA for this indication after a pivotal, phase III trial (Study 116) was stopped early, demonstrating that the combination of idelalisib and rituximab showed a statistically significant effect on progression-free survival (PFS).
“In less than a year, we have seen considerable progress in the availability of treatments for chronic lymphocytic leukemia,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, 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.”
Study 116 randomized 220 patients to receive the combination of idelalisib plus rituximab or placebo plus rituximab. The first interim analysis showed that the PFS in the experimental combination arm was 5.2 months greater than in the control arm (10.7 months vs 5.5 months).
According to the FDA, idelalisib is the third drug with a breakthrough designation to be approved to treat CLL. The FDA previously approved obinutuzumab (Gazyva) in November 2013, ibrutinib (Imbruvica) in February 2014 and designated CLL as a new indication for ofatumumab (Arzerra) in April 2014. Obinutuzumab and ofatumumab had also received the breakthrough therapy designation for CLL.
Idelalisib also received an accelerated approval for both FL and SLL. The oral phosphoinositide 3-kinase (PI3K) delta inhibitor is to be used for both indications after a patient has received at least two prior systemic therapies.
The accelerated approval of idelalisib for relapsed FL and SLL was based on a clinical trial that included 123 patients with indolent non-Hodgkin lymphoma. The study showed that 54% of the patients with relapsed FL and 58% of patients with relapsed SLL had an objective response.
Common side effects of idelalisib include diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash. Other common abnormalities include decreased levels of white blood cells (neutropenia), hypertriglyceridemia, hyperglycemia, and elevated liver enzyme levels.
The idelalisib label has a Boxed Warning for fatal and serious toxicities that can include liver toxicity, diarrhea and colitis, pneumonitis, and intestinal perforation. Idelalisib has a Risk Evaluation and Mitigation Strategy (REMS) which is a “communication plan to ensure healthcare providers who are likely to prescribe idelalisib are fully informed about these risks,” according to the FDA.