CombinatoRx’s Phase IIb osteoarthritis study fails endpoint

While there was a trend in favor of Synavive, and an observed dose-response relationship, the combination did not demonstrate statistical significance compared to placebo for WOMAC question #1 measuring pain while walking on a flat surface (the primary endpoint), nor when compared to prednisolone alone. However, Synavive was generally well tolerated and there were no serious adverse events reported. Analyses of the full dataset from the study remain ongoing, the company said.

In the study, patients were randomized to three different doses of Synavive (2.7mg prednisolone and 360mg, 180mg or 90mg of dipyridamole), 2.7mg of prednisolone alone or placebo. Patients were dosed for a total of 14 weeks (98 days) including an initial two-week dipyridamole titration phase. The primary endpoint of this study to assess the efficacy of Synavive compared to placebo was the change in WOMAC question #1 calculated from baseline to day 98.

Alexis Borisy, president and CEO of CombinatoRx, said: “The results contain some observations that are difficult to reconcile, and we intend to complete additional analysis of the data in order to further our understanding of Synavive’s biology and determine appropriate next steps.

“While these outcomes are a setback for the Synavive program, we remain convinced in the power of the CombinatoRx discovery platform and approach. We have many valuable assets, including CRx-401, our product candidate for Type 2 diabetes and CRx-197 for topical dermatology, both expecting Phase IIa clinical data in the next few months, as well as programs such as CRx-191 and new emerging programs such as in B-cell malignancies and a next generation version of Synavive.”