Cytokinetics announced Monday that the experimental drug CK-274 led to significant reductions from baseline compared to placebo in left ventricular outflow tract pressure gradients (LVOT-G) in patients with obstructive hypertrophic cardiomyopathy. The results from the Phase II REDWOOD-HCM study sent shares in the company up as much as 59%.
The trial included patients with symptomatic obstructive hypertrophic cardiomyopathy on background medical therapy who were randomised into one of two treatment cohorts or a placebo group. Patients in the first cohort received CK-274 once daily at doses of 5mg, 10mg and 15mg, while those in the second cohort were given 10mg, 20mg and 30mg doses of the oral, small molecule cardiac myosin inhibitor.
Top-line results showed that 92.9% of 14 patients who were in the second CK-274 cohort achieved the target goal of treatment, defined as an average resting LVOT-G of <30 mmHg and post-Valsalva gradient <50 mmHg at week 10, compared to 7.7% of the 13 participants in the placebo group. Cytokinetics added that 78.6% of the 14 subjects who were in cohort one also achieved the target goal of treatment.
The company said reductions in LVOT-G among patients given CK-274 occurred within two weeks of initiating treatment, were maximised within two to six weeks of the start of dose titration, and were sustained until the end of treatment at 10 weeks. Cytokinetics also noted that CK-274 was generally well tolerated, with no serious adverse events attributed to the drug and no treatment interruptions occurring. However, it said one patient on CK-274 experienced a "transient decrease" in left ventricular ejection fraction to <50% that required dose adjustment.
Fady Malik, Cytokinetics' executive vice president of R&D, remarked "these findings inform the design of our Phase III trial, in which we expect to titrate patients with a flexible dosing scheme of 5mg, 10mg, 15mg, and 20mg to personalise and maximise the potential treatment effect for patients." The registrational study is expected to start before the end of the year.
Other drugs targeting cardiac myosin include Bristol Myers Squibb's mavacamten, which is currently under review  by the FDA for patients with symptomatic obstructive hypertrophic cardiomyopathy, with a decision expected by January 28 next year. Bristol Myers Squibb gained the compound through its $13.1-billion purchase  of MyoKardia last year.