Gilead Sciences Moves Ahead on Idelalisib Filings

Founded in 1987, Gilead Sciences made a name for itself in 1996, when it launched Vistide, a treatment for cytomegalovirus retinitis in patients with AIDS. The company has expanded its understanding of the complexities of the immune system and is firmly focused on oncology.

Its lead oncology agent idelalisib is undergoing phase III investigation as a treatment for indolent non-Hodgkin lymphoma (iNHL) and chronic lymphocytic leukemia (CLL). Idelalisib, the prized asset that was acquired from Calistoga Pharmaceuticals in 2011, is aimed at a target identified as the “delta” variation of the PI3 kinase pathway. The target is involved in proliferation, growth, migration, and cell survival. When the pathway is switched into an overactive mode, it can lead to cancer and inflammatory diseases. Idelalisib is being developed both as a single agent and in combination with approved and investigational therapies.

“Idelalisib has produced impressive responses in clinical trials for both indolent NHL and CLL, and we believe that it may offer an important new treatment option for patients with these cancers,” said Roger Dansey, MD, vice president of Clinical Research at Gilead, in an interview with Oncology & Biotech News.

Combination treatment with idelalisib and rituximab (Rituxan) was associated with a >70% improvement in overall survival (OS) in patients with high-risk relapsed/refractory CLL, according to phase III data from Study 116 (Abstract LBA-6) presented at the 55th Annual Meeting of the American Society of Hematology. “This study was stopped early because of the overwhelming improvement in progression-free survival among patients receiving idelalisib plus rituximab versus those receiving rituximab alone,” said Dansey.

In the phase II Study 101-09 presented during an oral session of the same meeting (Abstract #85), “[heavily-pretreated] patients with refractory iNHL who received idelalisib had a 57% overall response rate, with a median duration of response of 12.5 months,” said Dansey.

The company reports that the FDA has granted priority review to a New Drug Application (NDA) for idelalisib for the treatment of relapsed CLL. A target review date under the Prescription Drug User Fee Act (PDUFA) has been set for August 6, 2014. Previously, the FDA granted idelalisib a Breakthrough Therapy designation in relapsed CLL. The designation is given to drug candidates that may offer major advances in treatment over existing options.

Separately, the FDA has accepted an NDA for idelalisib for the treatment of patients with iNHL. The FDA has granted a standard review for the iNHL NDA, with a target review date under PDUFA set for September 11, 2014.

Rounding out the company’s other oncology offerings are momelotinib, simtuzumab, GS-9973 (a Syk inhibit or), GS-9820 (a PI3K delta inhibitor), and GS-5745 (an MMP9 mAb inhibitor).

Momelotinib, an investigational JAK inhibitor that has shown promise for the treatment of myelofibrosis, is in phase III development and the others are in earlier stages.

Gilead Pipeline

*Being developed as a single agent and in combination with idelalisib