Idelalisib (Zydelig) Approved for CLL and Lymphoma

Zosia Chustecka

July 23, 2014

A much anticipated new oral drug that has generated great excitement within hematologic malignancies circles has been approved in the United States. The first-in-class kinase inhibitor idelalisib (Zydelig, Gilead) can now be used in the treatment of chronic lymphocytic leukemia (CLL) and for 2 types of lymphoma in patients who have relapsed after previous treatment.

The US Food and Drug Administration (FDA) granted a full approval for idelalisib in relapsed CLL, specifically for its use in combination with rituximab (Rituxan) in patients for whom rituximab alone would be considered appropriate therapy due to other existing medical conditions (comorbidities).

The approval of this indication was based on a placebo-controlled trial in 220 patients that was stopped early for benefit. The first prespecified interim analysis showed a significantly longer progression-free survival in patients treated with idelalisib plus rituximab (10.7 months) compared with those on placebo plus rituximab (5.5 months). Results from a second interim analysis continued to show a statistically significant improvement, the FDA noted.

This study was published earlier this year in the New England Journal of Medicine, as reported at the time by Medscape Medical News. Lead author Richard Furman, MD, from the Weill Cornell Medical College in New York City, concluded that the addition of idelalisib to rituximab "provided effective durable disease control and improved overall survival for patients with relapsed CLL who were not suitable for cytotoxic chemotherapy, including high-risk patients."

Some of the responses seen with idelalisib were "incredible" and were seen within a week, Dr. Furman said. "It is remarkable how quickly idelalisib worked in this heavily treated group of patients, many of whom were resistant to chemotherapy.... Their cancer quickly melted away."

"The treatment today for CLL can be worse than the disease, leading to a great deal of side effects and death. This study, along with others we have conducted on idelalisib, demonstrates that we may no longer need to use chemotherapy in CLL," Dr. Furman commented at the time.

Accelerated Approval for Lymphoma

The FDA also granted accelerated approval for idelalisib for use in relapsed follicular B-cell non-Hodgkin's lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL), another type of non-Hodgkin's lymphoma. Idelalisib is intended to be used in patients who have received at least 2 prior systemic therapies, the agency noted.

This indication is based on a clinical trial with 123 participants with indolent non-Hodgkin's lymphomas, which has also been published and "raised eyebrows" when it was presented at the Annual Society of Hematology.

These lymphoma patients had become refectory to both rituximab and alkylating agents, and they represent "an unmet medical need," the study authors commented at the time. All patients were treated with idelalisib, and the results showed an overall response rate of 54% in patients with relapsed FL and 58% in patients with SLL.

The accelerated approval program allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate end point reasonably likely to predict clinical benefit to patients, the FDA explained. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.

Idelalisib had both breakthrough therapy designation and orphan drug designation.

It is the fifth new drug with breakthrough therapy designation to be approved by the FDA, and the third drug with this designation approved to treat CLL, the agency noted.

Boxed Warning and REMS

Idelalisib carries a boxed warning alerting patients and healthcare professionals of fatal and serious toxicities that can occur, including liver toxicity, diarrhea and colon inflammation (colitis), lung inflammation (pneumonitis), and intestinal perforation. There is also a Risk Evaluation and Mitigation Strategy (REMS) with a communication plan to ensure healthcare providers who are likely to prescribe this drug are fully informed about these risks.

Common adverse effects include diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash, the FDA notes. Common laboratory abnormalities include neutropenia, hypertriglyceridemia, hyperglycemia, and elevated levels of liver enzymes.


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