Cardiac myosin inhibitor may benefit in obstructive hypertrophic cardiomyopathy
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Cytokinetics announced a phase 2 trial of its novel cardiac myosin inhibitor in patients with obstructive hypertrophic cardiomyopathy was successful.
The company released top-line results of the REDWOOD-HCM trial of the next-generation cardiac myosin inhibitor (CK-274). According to a press release, the results provide answers about dose selection and allow progression to a phase 3 clinical trial, which is scheduled to begin by the end of 2021.
The drug “interacts with the structural apparatus of the heart to essentially decrease the number of interactions that are occurring between the myosin head and the acting filament, the structural proteins of the heart,” Martin S. Maron, MD, director of the Hypertrophic Cardiomyopathy Center and Research Institute at Tufts Medical Center and principal investigator of the trial, said in an interview. “CK-274 decreases the force of contractility of the heart, and by doing that, a number of beneficial effects can be seen in patients with obstructive hypertrophic cardiomyopathy, which include lowering the pressure gradient, resulting in an improvement in heart failure symptoms.”
Maron and colleagues enrolled 41 patients in the trial and randomly assigned them on a 2:1 basis to CK-274 or placebo. In the first cohort, patients received an escalating dose of 5 mg, 10 mg and 15 mg. In the second cohort, patients received an escalating dose of 10 mg, 20 mg and 30 mg.
At 10 weeks, the CK-274 group had greater reduction in average resting left ventricular outflow tract pressure gradient and average post-Valsalva resting LV outflow tract pressure gradient (P < .001 for both), according to the release.
The target goals of resting gradient less than 30 mm Hg and post-Valsalva resting gradient less than 50 mm Hg were met in 78.6% of patients in the first cohort assigned CK-274 and in 92.9% of patients in the second cohort assigned CK-274 compared with 7.7% of the pooled placebo group, the company stated in the release.
Adverse events were similar in the CK-274 and placebo groups, and no treatment-related serious adverse events were reported, according to the release.
“What we learned was what the dose range for CK-274 looks like in terms of giving a physiologic effect that we want to see, which is lowering the gradient without reducing significantly the overall heart systolic function,” Maron told Healio. “The results exceeded my expectations in terms of two things: the effect of the drug at reliably and relatively rapidly lowering the pressure gradient to levels that would be significant in terms of translating to a symptomatic benefit, and that effect was associated with very low to any risk. All patients stayed on the drug.”
In the phase 3 trial, outcomes will include functional capacity assessments such as peak oxygen concentration, Maron said in an interview.
For more information:
Martin S. Maron, MD, can be reached at Tufts Medical Center, 800 Washington St. #70, Boston, MA 02111; email: mmaron@tuftsmedicalcenter.org.
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