On June 12, 2017 Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative therapeutics to treat serious and rare diseases, reported that the DART Phase 2 study of dalantercept plus axitinib did not achieve its primary endpoint in advanced renal cell carcinoma (RCC) (Press release, Acceleron Pharma, JUN 12, 2017, View Source [SID1234519496]). The primary efficacy endpoint of the study was to demonstrate a statistically significant increase in progression-free survival (PFS) for treatment of dalantercept plus axitinib versus placebo plus axitinib in advanced RCC patients.

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"We designed a robust Phase 2 study to evaluate the efficacy of dalantercept in combination with anti-VEGF therapy in advanced renal cell carcinoma patients whose disease has progressed on prior anti-VEGF therapy. We are disappointed by the results given the need for new agents that improve outcomes for patients with advanced RCC. We would like to thank the patients, caregivers, investigators, and our team who made the DART study possible," said Habib Dable, President and Chief Executive Officer of Acceleron. "Based on the lack of efficacy, we are discontinuing the development of dalantercept. We remain focused on the development of luspatercept across multiple Phase 3 and Phase 2 studies and ACE-083 across two neuromuscular diseases, and will continue to pursue additional candidates in areas of high unmet medical need."

The DART study enrolled 131 patients with advanced RCC. The efficacy data are based on the All-Treated Set (ATS) which is defined as all randomized patients who received any study drug (n=119) as of the database cutoff. In the ATS, 58 patients were randomized to dalantercept plus axitinib and 61 patients were randomized to placebo plus axitinib.

The median PFS for dalantercept plus axitinib was 6.8 months versus 5.6 months for placebo plus axitinib. Dalantercept plus axitinib did not decrease the rate of disease progression or death (HR 1.11, two-sided 95% CI [0.71, 1.73], one-sided p-value 0.67). The key secondary endpoint for the study was PFS for patients who received two or more prior systemic anti-cancer therapies. In this analysis, the median PFS for dalantercept plus axitinib was 8.1 months versus 7.0 months for placebo plus axitinib (HR 0.78, two-sided 95% CI [0.33, 1.87], one-sided p-value 0.29). The confirmed objective response rate (ORR) for dalantercept plus axitinib was 19% versus 25% for placebo plus axitinib (p-value 0.43, Cochran-Mantel-Haenszel test).

The safety data are based on the 119 ATS patients. The frequency of Grade 3 or higher adverse events (AEs) regardless of causality were similar overall in the dalantercept plus axitinib (59%) and the placebo plus axitinib (64%) study arms. The frequency of serious AEs of any grade regardless of causality were also similar in the dalantercept plus axitinib (29%) and the placebo plus axitinib (26%) study arms. The AEs associated with dalantercept were consistent with those previously observed.

About the DART Phase 2 Study

The Phase 2 DART clinical trial is a two-part study in patients with advanced renal cell carcinoma. Part 1 is a dose-escalation study of dalantercept plus axitinib to evaluate the safety and tolerability of the combination in patients whose disease has progressed following one to three lines of prior therapy. Part 2 is a randomized, double-blind study of 130 patients with advanced renal cell carcinoma who have progressed following treatment with a VEGF receptor tyrosine kinase inhibitor. Patients may have also received prior mTOR therapy and/or immunotherapy. For additional information on this clinical trial, please visit www.clinicaltrials.gov, identifier NCT01727336.

About Dalantercept

Dalantercept is an investigational protein therapeutic that inhibits angiogenesis by preventing BMP9, a protein in the transforming growth factor-beta (TGF-beta) superfamily, from interacting with activin receptor-like kinase 1 (ALK1), a cell-surface receptor found on proliferating vascular endothelial cells. Dalantercept inhibits ALK1 signaling, which is required for the development of mature, functional vasculature.