Cytokinetics HCM Drug Poised to Begin Phase III
California-based late-stage biopharmaceutical company Cytokinetics has announced positive results from its Phase II clinical trial for a new type of treatment for hypertrophic cardiomyopathy (HCM). The firm would be moving forward to Phase III, which is expected to commence before the end of 2021.
In a press release, Cytokinetics detailed favorable topline results from Cohorts 1 and 2 of REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM). Throughout the ten weeks of the observation period, the researchers found significant reductions from baseline in the average resting left ventricular outflow tract pressure gradient (LVOT-G) and the average post-Valsalva LVOT-G, compared to the placebo group. CK-274 is a new, oral, small molecule cardiac myosin inhibitor designed to reduce the hypercontractility linked with HCM.
The majority of the patients, 78.6% from Cohort 1 and 92.9% from Cohort 2, achieved their target goal, explicitly having a resting gradient of <30 mmHg and post-Valsalva gradient of <50 mmHg after ten weeks. The placebo group logged only 7.7%.
The researchers started seeing the reductions after only two weeks of starting the treatment, which peaked at around two to six weeks and stayed sustained by the tenth week. The declines were dependent on the dose, where increased doses of CK-274 translated to more significant LVOT-G reductions.
REDWOOD-HCM is a multi-center, randomized, double-blind, placebo-controlled trial on patients who have been diagnosed with symptomatic obstructive HCM (oHCM). The main objective is to establish the treatment's safety and tolerability, while the secondary goals were to describe the concentration-response relationship on the treatment on resting and post-Valsalva left ventricular outflow tract gradient, to be measured at ten weeks using an echocardiogram.
Another positive finding was that the REDWOOD-HCM was generally well tolerated throughout the trial. There were no treatment interruptions and no serious adverse effects. There were also no new cases of atrial fibrillation.
"The combined data from Cohorts 1 and 2 in REDWOOD-HCM met our high expectations for this trial of CK-274 in patients with obstructive HCM, given the observed onset of response to initiation of treatment, magnitude and breadth of response, reversibility of LVEF decreases and favorable tolerability profile," Fady I. Malik, M.D., Ph.D., the executive vice president of research and development at Cytokinetics, was quoted as saying.
Dr. Malik added that the results would determine the design of its Phase III trial, during which time the patients will be given flexible doses of CK-274 in 5mg, 10mg, 15mg, and 20mg depending on their treatment needs.
Cytokinetics is known for discovering, developing, and commercializing muscle activators and muscle inhibitors to treat debilitating diseases that compromise muscle performance. The company has several advance phase trials ongoing, including a U.S. NDA submission of omecamtiv mecabril for patients with health failure and reldesemtiv for ALS, among many others.