Cytokinetics, Incorporated (CYTK) today announced that it has received feedback from the U.S. Food and Drug Administration (FDA) that the Six Minute Walk Test (6MWT) is an acceptable primary efficacy endpoint for a potential registration program for reldesemtiv in patients with spinal muscular atrophy (SMA) who have maintained ambulatory function. The FDA also recommended adding a global function scale as a secondary endpoint, such as the Hammersmith Functional Motor Scale – Expanded (HFMSE). In collaboration with Astellas, Cytokinetics is developing reldesemtiv as a potential treatment for people with SMA and certain other debilitating diseases and conditions associated with skeletal muscle weakness and/or fatigue. The companies are discussing potential next steps regarding the ongoing development program for reldesemtiv in this patient population.
Results from a Phase 2 clinical study of reldesemtiv in patients with SMA showed a statistically significant exposure-response relationship in changes from baseline in Six Minute Walk Distance (6MWD), a sub-maximal exercise test of aerobic capacity and endurance. The study also showed statistically significant increases for Maximal Expiratory Pressure (MEP), a measure of strength of respiratory muscles. Other assessments, including the HFMSE, did not demonstrate differences between reldesemtiv versus placebo. Adverse events in the Phase 2 study in patients with SMA were similar between treatment groups receiving reldesemtiv and placebo.
Cytokinetics is preparing to conduct an additional Phase 1 study of reldesemtiv in healthy volunteers designed to assess whether higher doses than were evaluated in the Phase 2 study of patients with SMA may result in higher plasma concentrations. This study is expected to begin in the first quarter.
Cure SMA Funding for Combination Therapies
The clinical trials for CK-2127107 (reldesemtiv) came about because of early seed funding from Cure SMA, supporting research focused on the potential application of these types of skeletal muscle activators to SMA. In 2014, Cytokinetics released encouraging data from preclinical studies conducted with our funding. The data showed this approach had positive effects in preserving muscle strength and reducing muscle fatigue, setting the groundwork for the ongoing clinical trials.
The progress of this program also highlights the importance of developing combination therapies to treat SMA. The goal is that CK-2127107 will show positive results in preserving muscle strength in human clinical trials and may lend itself to combination with other SMA therapies, particularly those that address the SMN protein deficiency caused by the SMN1 mutation. Furthermore, Reldesemtiv has the potential to be a valuable therapeutic option for different ages and stages of disease from pediatric and adult patients with Type II, Type III, or Type IV disease.