Ninerafaxstat demonstrates good tolerability and safety in non-obstructive HCM patients

Ninerafaxstat demonstrates good tolerability and safety in non-obstructive HCM patients

The investigational drug ninerafaxstat demonstrated a good tolerability and safety profile and evidence of improvements in symptoms and exercise performance in people with nonobstructive hypertrophic cardiomyopathy (HCM), according to results from a 12-week phase 2 study presented at the American College of Cardiology Annual Scientific Meeting.

Ninerafaxstat is designed to help the heart work more efficiently by changing how muscles use energy, partially inhibiting the use of fatty acids for fuel and promoting the use of glucose instead. While the IMPROVE-HCM trial primarily focused on the tolerability and safety of the drug, depending on the results of future clinical trials, it could help people with nonobstructive HCM overcome fatigue, chest discomfort, and other activity-limiting symptoms of the condition, for which there are few existing treatments.

Our results raise excitement that a novel drug therapy with ninerafaxstat may offer nonobstructive HCM patients the opportunity to achieve a better quality of life by reducing symptom burden and improving physical performance. The safety and tolerability of the drug in this phase 2 study was excellent. These data strongly support the transition to Phase 3 development.”

Martin S. Maron, MD, cardiologist and director of the Hypertrophic Cardiomyopathy Center at Lahey Hospital and Medical Center in Burlington, Massachusetts, and lead author of the study

HCM is the most common genetic heart disease worldwide, affecting an estimated 1 in 500 people. This causes the heart muscle to become stiff and thick, making it difficult for the heart to pump blood properly and increasing the risk of sudden cardiac death. Several treatment options are available for about two-thirds of patients with the obstructive form of the disease, in which the thickened muscle makes it difficult for blood to drain from the heart. However, for the remaining patients there are only limited treatment options. Third of patients who have the non-obstructive form.

Most people with non-obstructive HCM have no symptoms, but about 40% experience symptoms such as chest pain, shortness of breath, irregular heartbeat, dizziness, fainting, and swelling, which often worsen over time.

"There is no doubt that the greatest unmet treatment need for HCM is in non-obstructive patients who experience disabling symptoms. They are very frustrated by the impact of symptoms on their quality of life in the absence of approved medical therapies," said Maron.

For the phase 2 study, researchers recruited 67 patients treated for nonobstructive HCM at 14 centers. Participants were randomly assigned to receive either Ninerafaxstat or a placebo for 12 weeks.

At the end of this period, researchers found no significant difference in the rate of adverse events between the two study groups, suggesting that the drug was not associated with an increased risk of adverse events. There were also no adverse events related to low ejection fraction (a measure of how well the heart pumps blood) and no negative effects on blood pressure or heart rate.

In addition, patients taking the drug showed improvements in secondary endpoints including ventilatory efficiency - a measure of cardiac performance during exercise - and reduced left atrial size, evidence that the drug worked as designed. There was no overall difference between the two study groups on the Kansas City Cardiomyopathy Questionnaires (KCCQ), a well-established method for assessing the quality of life of people with heart problems, but there was a nine-point improvement in the subgroup of participants who took ninerafaxstat reported having significant symptoms at the start of the study compared to symptomatic patients taking a placebo.

"If you restrict the study's analysis to patients who were particularly symptomatic at baseline, there was a significant improvement in KCCQ scores in these patients compared to placebo, suggesting that these patients felt much better with the drug," Maron said.

Because it was a phase 2 study, the study had a relatively small sample size and was primarily designed to assess the tolerability and safety of the drug. Maron said a larger Phase 3 trial would help shed light on the extent of the drug's potential benefits. In addition, separate clinical trials are ongoing to evaluate the drug's potential benefit for people with angina (chest pain) and heart failure with preserved ejection fraction.

The study was funded by Imbria Pharmaceuticals, the developer of Ninerafaxstat.

This study was simultaneously published online inJournal of the American College of Cardiologyat the time of presentation.

For more information about hypertrophic cardiomyopathy, visit CardioSmart.org/HCM.

Maron will be available to the media in a press conference on Monday, April 8, 2024 at 10:00 a.m. ET / 2:00 p.m. UTC in Room B203.

Maron will present the study, “Efficacy and Safety of Ninerafaxstat, a Novel Cardiac Mitotrope, in Patients with Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results of IMPROVE-HCM,” on Monday, April 8, 2024, at 8:30 a.m. ET/12:30 UTC in the Main Tent in Hall B-1.

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