Idelalisib CLL Trial Shows Strong Results, Stopped Early

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Gilead Sciences, based in Foster City, California, will stop a phase III trial of the new drug idelalisib early thanks to highly significant efficacy of the drug among patients with previously treated chronic lymphocytic leukemia (CLL). The company has informed the US Food and Drug Administration (FDA) of the early termination, and data from the planned interim analysis of the study will be presented at an upcoming scientific meeting.

“Given the significant unmet medical need in CLL, particularly in this population of patients who are not fit for chemotherapy, we are pleased that idelalisib has shown a clinically meaningful benefit for patients,” said Norbert W. Bischofberger, PhD, the chief scientific officer and executive vice president at Gilead, in a press release.

The trial, a phase III study known as Study 116, was a randomized, double-blind, placebo-controlled trial that enrolled 220 patients with CLL. All patients had undergone prior treatment and subsequently recurred, and all had measurable lymphadenopathy. CLL progression must have occurred less than 24 months since the completion of the last prior therapy, and patients could not be eligible for cytotoxic therapy because of chemotherapy-induced bone marrow damage or other comorbidities.

Patients received eight infusions of rituximab over 24 weeks, as well as either idelalisib 150 mg twice daily or placebo. The study was conducted at 72 centers and was led by Gilead’s Thomas Jahn, MD. After the planned interim analysis showed significant benefit (the primary endpoint is progression-free survival), those randomized to placebo will be eligible to join a continuation study and receive open-label idelalisib. The company is also planning an expanded access program in which patients with recurrent CLL who are not candidates for chemotherapy would receive the drug.

Idelalisib has also shown good results in indolent non-Hodgkin lymphoma, and Gilead submitted a New Drug Application to the FDA for that indication in September. They plan on seeking approval for the drug in the European Union by the end of this year. Idelalisib inhibits phosphoinositide 3-kinase (PI3K) delta, a pathway that is hyperactive in various hematologic malignancies.

“This is the first phase III study to report positive results for a new class of targeted therapies that inhibit B-cell receptor signaling as a major component of their mechanism of action, an important area of focus in the development of chemotherapy-free regimens in CLL and other B-cell malignancies,” Dr. Bischofberger said.