Gilead Sciences, Inc., a biopharmaceutical company, has reported results of a phase II study (Study 101-09) evaluating idelalisib, an investigational oral inhibitor of PI3K delta, for the treatment of patients with indolent non-Hodgkin's lymphoma (iNHL) that is refractory (non-responsive) to rituximab and to alkylating-agent-containing chemotherapy. In this study, single-agent treatment with idelalisib achieved an overall response rate of 57 per cent with a median duration of response of 12.5 months.

This data were presented during an oral session at the Annual Meeting of the American Society of Hematology (ASH) in New Orleans.

"It has been more than ten years since a treatment with a novel mechanism of action has been approved for indolent NHL, underscoring the medical need for new treatments for patients who are no longer responsive to currently available therapies," said Ajay Gopal, MD, associate professor, University of Washington School of Medicine and associate member, Clinical Research Division, Fred Hutchinson Cancer Research Centre in Seattle, Washington. "The overall response rate and durability of response observed in this study suggest that idelalisib may become a valuable new therapy for iNHL patients who have very limited treatment options."

Of the 71 patients who responded to therapy, seven (six per cent) achieved a complete response, 63 (50 per cent) had a partial response and one (one per cent) had a minor response. Among patients who responded, the median duration of response was 12.5 months and the median time to response was 1.9 months. Median progression-free survival for all patients was 11.0 months and median overall survival was 20.3 months. Ninety per cent of patients experienced shrinkage in lymph node size.

The most common Grade greater-than or equal to three adverse event was diarrhoea, which was reported in 16 patients (13 per cent). Grade greater-than or equal to 3 transaminase elevations (a measure of liver function) were reported in 16 patients (13 per cent). Of the 16 patients who had Grade greater-than or equal to 3 transaminase elevations, 14 were retreated with idelalisib and of those, 10 (71 per cent) had no recurrence. Grade greater-than or equal to 3 neutropenia occurred in 34 patients (27 per cent). Twenty-five patients (20 per cent) discontinued therapy because of adverse events.

These results in iNHL support Gilead's recent regulatory filings for idelalisib in the United States and European Union. On September 11, 2013, Gilead submitted a New Drug Application to the US FDA for idelalisib for the treatment of refractory iNHL. Following Gilead's NDA submission for iNHL, FDA granted idelalisib a Breakthrough Therapy designation for chronic lymphocytic leukaemia (CLL) in relapsed patients. Gilead is now engaging in a dialogue with the FDA regarding a regulatory filing in CLL.

Gilead's Marketing Authorization Application (MAA) for idelalisib for the treatment of iNHL and CLL was validated by the European Medicines Agency (EMA) on November 20. Review of the MAA will be conducted under the centralized licensing procedure, which, when finalized, provides one marketing authorization in all 28 member states of the European Union (EU). The Committee for Medicinal Products for Human Use (CHMP) has accepted Gilead's request for accelerated assessment for idelalisib, a designation that is granted to new medicines of major public health interest. Although accelerated assessment could shorten the review time of idelalisib by approximately two months, it does not guarantee a positive opinion from the CHMP or final approval by the European Commission. If approved, idelalisib could be available for marketing in the EU in the second half of 2014.

Study 101-09 is a phase II, open-label, single-arm efficacy and safety study of idelalisib in patients with previously treated iNHL that is refractory both to rituximab and to alkylating-agent-containing chemotherapy (refractory defined as no response while on therapy or progression within six months of completion of therapy).

The study enrolled 125 patients from approximately 50 study sites in the United States and Europe. Patients were a median age of 64 and had confirmed diagnoses of follicular lymphoma (n=72), small lymphocytic lymphoma (n=28), lymphoplasmacytic lymphoma/ Waldenström macroglobulinemia (n=10) or marginal zone lymphoma (n=15). Patients had received a median of four prior treatment regimens before study entry, with 79 per cent of patients refractory to two or more prior regimens and 90 per cent refractory to their most recent regimen. All patients received idelalisib 150 mg twice daily and are allowed to continue daily dosing as long as they benefit from therapy. The primary endpoint of the study is overall response rate, defined as the proportion of patients achieving a confirmed complete or partial response with idelalisib treatment (response definitions based on standard criteria; responses assessed by study investigators and an independent review committee).

Idelalisib is an investigational, highly selective oral inhibitor of phosphoinositide 3-kinase (PI3K) delta. PI3K delta signaling is critical for the activation, proliferation, survival and trafficking of B lymphocytes and is hyperactive in many B-cell malignancies. Idelalisib is being developed both as a single agent and in combination with approved and investigational therapies.

Gilead's clinical development programme for idelalisib in iNHL includes Study 101-09 in highly refractory patients and two phase III studies of idelalisib in previously treated patients. In addition to Study 116, the development programme in CLL includes two ongoing phase III studies of idelalisib in previously treated patients. Combination therapy with idelalisib and GS-9973, Gilead's novel spleen tyrosine kinase (Syk) inhibitor, also is being evaluated in a phase II trial of patients with relapsed or refractory CLL, iNHL and other lymphoid malignancies.

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need.