WASHINGTON – Treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy who remained on treatment with the investigational agent mavacamten for a median of 62 weeks continued to show the same level of safe response to the drug as seen after the first 30 weeks on treatment in the pivotal trial for this agent.
The new findings from longer-term treatment bode well for mavacamten. That’s because if the drug is used in routine practice to avoid the need for surgery or an invasive intervention to reduce blockage of a patient’s left ventricular outflow tract, the duration of mavacamten treatment will likely need to continue for many years and even for decades, said Florian Rader, MD, who presented the results at the annual scientific sessions of the American College of Cardiology.
“In practice, mavacamten will probably be used for many, many years, especially as it replaces septal-reduction therapy, so we need long-term data,” noted Dr. Rader during a press briefing on his report. “I’m very happy with the long-term data” in the follow-up study.
The Food and Drug Administration is currently considering whether to approve mavacamten for routine marketing to treat patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), with a decision expected by the end of April 2022.
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The study Dr. Rader reported followed 231 patients with symptomatic oHCM who had completed the 30-week pivotal trial of mavacamten, EXPLORER-HCM, and opted to continue on open-label extended treatment with mavacamten, either continuing the treatment they started during the trial or crossing over to receive mavacamten after receiving placebo during the trial.
The major findings from EXPLORER-LTE (long-term extension) were that continued treatment for a median of about 62 weeks maintained the safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase, said Dr. Rader, codirector of the Clinic for Hypertrophic Cardiomyopathy and Aortopathies at Cedars-Sinai Medical Center in Los Angeles.
Mavacamten represents “an almost revolutionary change” for treating oHCM, commented Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis. “Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” said Dr. Guglin during the press briefing.
“All of us who care for patients with oHCM have looked forward to having a disease-specific therapy. It is encouraging to see that the safety and efficacy remained high with long-term follow-up,” commented Kyle W. Klarich, MD, a professor and cardiologist who specializes in treating patients with HCM at the Mayo Clinic in Rochester, Minn.
Mavacamten is a direct myosin inhibitor that reduces the excess number of myosin-actin cross bridges that form in patients with oHCM, and thereby directly targets the pathophysiology that underlies the disorder, explained Dr. Rader.
The patients on mavacamten included in the long-term extension reported by Dr. Rader averaged 60 years of age, and 61% were men. They averaged a 35.6–mm Hg drop in their resting left ventricular outflow tract (LVOT) gradient after 48 weeks on treatment, and a 32.8–mm Hg reduction after 84 weeks. When the investigators measured their LVOT gradient during a valsalva maneuver, their reductions from baseline averaged 45.3 mm Hg after 48 weeks and 46.4 mm Hg after 84 weeks.
Resting left ventricular ejection fraction also fell, by an average of 7.0 percentage points from baseline after 48 weeks, and by an average of 9.0 percentage points after 84 weeks. After 48 weeks on treatment, 68% of patients had at least a one-class improvement from baseline in their New York Heart Association functional class.
The safety results showed that most treatment-related adverse events were mild or moderate, and about 2% of patients had a serious drug-related adverse event. Ten of the 231 patients discontinued mavacamten because of a treated-related adverse event.
EXPLORER-HCM and EXPLORER-LTE were sponsored by MyoKardia, the company that is developing mavacamten and which is now owned by Bristol-Myers Squibb. Dr. Rader has been a consultant to MyoKardia as well as to Medtronic and ReCor. Dr. Guglin and Dr. Klarich had no disclosures.