Imbria Pharmaceuticals announced a strategic partnership with the Hypertrophic Cardiomyopathy Association (HCMA) to accelerate patient recruitment for the FORTITUDE-HCM Phase 2b clinical trial, which is evaluating ninerafaxstat as a potential first treatment for symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM). The collaboration addresses a critical unmet medical need, as nHCM currently has no approved therapeutic options despite affecting an estimated 250,000-400,000 patients in the United States.
Novel Mechanism Targets Cardiac Energy Metabolism
Ninerafaxstat represents an innovative approach to treating cardiac diseases characterized by energy supply and demand imbalances in the heart. As a partial fatty acid oxidation (pFOX) inhibitor, the investigational therapy works by shifting the heart's metabolic preference from fatty acids toward glucose utilization. This metabolic shift leads to more efficient mitochondrial energy generation with the potential for improved cardiac function both at rest and during exercise, without adverse effects on left ventricular ejection fraction, heart rate, or blood pressure.
"Ninerafaxstat is a differentiated, first-in-class cardiovascular therapy," according to Imbria's company description. "A pipeline-in-a-pill, it has broad potential utility by improving cardiac energetics without adverse effects on heart rate, rhythm, ejection fraction, or blood pressure."
FORTITUDE-HCM Trial Design and Endpoints
The FORTITUDE-HCM study (NCT07023614) is a global, multicenter, double-blind, parallel-group, placebo-controlled Phase 2b clinical trial enrolling approximately 165 patients with nHCM. Participants receive either ninerafaxstat 200 mg twice daily or placebo. The primary endpoint measures change from baseline in the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), while secondary endpoints include additional symptom measurements from the KCCQ and functional capacity assessments using standardized cardiopulmonary exercise testing (CPET).
Enrollment is currently underway in the United States, with additional sites in the European Union and the United Kingdom anticipated to begin enrolling by the end of 2025. The trial builds on Phase 2a data that demonstrated "compelling safety and efficacy potential in an approvable endpoint," according to Imbria.
Addressing Significant Unmet Medical Need
Non-obstructive hypertrophic cardiomyopathy affects approximately one-third of all people with HCM, making it a substantial patient population with limited treatment options. In nHCM, abnormal thickening of the heart muscle impairs blood flow out of the heart, forcing the heart muscle to work harder to pump blood throughout the body. Patients experience a high burden of heart failure symptoms and face risks of adverse disease complications, including irregular heart rhythms.
"Every step forward in clinical research brings us closer to improving the lives of those living with nHCM," said Lisa Salberg, Founder and CEO of HCMA. "By supporting patient recruitment for FORTITUDE-HCM and spotlighting this collaboration at our annual meeting, we aim to increase awareness of this potential treatment and connect patients and families with meaningful opportunities to advance research and improve care."
Strategic Partnership to Enhance Patient Access
The partnership leverages HCMA's extensive network and patient advocacy expertise to educate the HCM community about the FORTITUDE-HCM study. HCMA will promote awareness through its outreach programs, conferences, patient communications, and surveys to help connect patients and clinicians with trial information and enrollment resources. The collaboration will be highlighted at the upcoming HCMA Annual Patient Meeting on October 18, 2025, where Imbria serves as a sponsor.
"Initiating the FORTITUDE-HCM trial to evaluate ninerafaxstat for nHCM represents a major milestone for Imbria and further validates our commitment to patients and families affected by this disease," said Alvin Shih, MD, Imbria's Chief Executive Officer. "We are proud supporters of the HCMA and its dedicated work on behalf of this patient community, and we look forward to working with Lisa and her team to accelerate the development of therapies for nHCM."
Broader Pipeline Potential
Beyond the current nHCM indication, Imbria has plans to initiate a Phase 2b clinical trial evaluating ninerafaxstat in heart failure with preserved ejection fraction (HFpEF), described as "a large and growing unmet need." The Boston-area company is backed by a syndicate of investors including RA Capital, SV Health Investors, Deep Track Capital, Catalio Capital Management, AN Ventures, and Cytokinetics.
