UPDATE: Gilead Reports Updated Phase 2 Results for Investigational GS-9973, Showed 49% Overall Response Rate with Est. Progression-Free Survival Rate at 24 Weeks 70%

Gilead Sciences, Inc. GILD today announced updated interim results of a Phase 2 study (Study 102) evaluating GS-9973, its investigational oral inhibitor of spleen tyrosine kinase (Syk), for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL). In this study, single-agent treatment with GS-9973 achieved an overall response rate of 49 percent, with an estimated progression-free survival (PFS) rate at 24 weeks of 70 percent. Detailed results will be presented today during an oral session at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstract #7007). “Most CLL patients eventually relapse following treatment, underscoring the need for novel therapies targeting survival pathways that may enable patients to obtain control of their disease without requiring chemotherapy,” said Jeff Sharman, MD, lead study author and Medical Director of Hematology Research for the US Oncology Network. “The strong response rates and acceptable safety profile seen in this study suggest that GS-9973 has the potential to provide therapeutic benefit for relapsed CLL patients.” The efficacy analysis focuses on a cohort of 41 CLL patients with a median exposure of 32 weeks (range 1-53) in Study 102. Among this cohort, the Kaplan-Meier estimated PFS rate at 24 weeks was 70 percent (95 percent CI: 51-83 percent). Median PFS and median duration of response were not reached. At the time of data snapshot, 46 percent of patients (n=19) continued GS-9973 treatment. There was a 49 percent (n=20) overall response rate, of which all were partial responses. Ninety-five percent of evaluable patients (n=37/39) experienced tumor shrinkage, including all 25 patients with a chromosome 17p deletion and/or a mutation in the TP53 gene or other genetic abnormalities that have been linked to poor prognosis. Sixty-two percent of evaluable patients (n=24) achieved at least a 50 percent tumor reduction. The safety of GS-9973 was also assessed in a larger population of 145 CLL or non-Hodgkin lymphoma (NHL) patients with an overall median exposure of 13 weeks at the time of data snapshot. Non-hematologic Grade ≥3 adverse events included fatigue (6.9 percent); dyspnea (6.2 percent); pneumonia (4.1 percent); nausea (3.4 percent); atrial fibrillation, chest pain, dehydration, febrile neutropenia and hypoxia (2.8 percent each); and back pain, hypotension, pyrexia and sepsis (2.1 percent each). Reversible Grade ≥3 transaminase elevations (a measure of liver function) were reported in 14 percent of patients. Based on these data, Gilead plans to initiate new CLL study cohorts to include patients who have relapsed following treatment with other inhibitors of the b-cell receptor (BCR) pathway. About Study 102 This Phase 2, open-label, single-arm safety and efficacy study is evaluating GS-9973 (800 mg twice daily) in patients with relapsed or refractory CLL and NHL (indolent NHL, diffuse large B-cell lymphoma and mantle cell lymphoma). The median age of the CLL patients included in the analysis was 73 years. These patients had received a median of two prior treatment regimens (e.g., anti-CD20 antibodies, alkylating agents, fludarabine) before study entry (range: 1-8). The primary endpoint of the study is progression-free survival at week 24 for the CLL cohort. Patients are allowed to continue daily dosing as long as they benefit from therapy. The study is ongoing. Initial results were presented at the American Society of Hematology Annual Meeting in December 2013.