We are inching closer to a treatment for nonobstructive hypertrophic cardiomyopathy after Cytokinetics presented the full results from the ACACIA-HCM trial, showing that its cardiac myosin inhibitor, MYQORZO (aficamten), meaningfully improves how nHCM patients feel and function.
- Unlike obstructive HCM, nHCM has no approved treatment.
- This means about half the HCM population has no targeted therapeutic options.
- Bristol Myers Squibb’s cardiac myosin inhibitor, mavacamten, showed no clinical benefit in the ODYSSEY-HCM trial.
ACACIA-HCM’s design focused on two parallel primary endpoints that measured both symptom burden and exercise capacity at 36 weeks in 517 randomized adults (KCCQ score and peak VO2) each with a miniscule p-value of 0.025 or less.
As we already know from the topline results in May of 2026, both primary endpoints were met.
- Patients’ KCCQ scores improved 11.4 points with aficamten versus 8.4 with placebo.
- Peak VO2 rose 0.64 ml/kg/min with aficamten while staying unchanged on placebo.
But the full picture reveals only some of the secondary endpoints reinforced aficamten’s benefits.
- Aficamten significantly improved NYHA functional class (41.9% vs. 27.8%), composite CPET z-scores, and NT-proBNP.
- However, it missed statistical significance for improving left atrial volume index and showed no benefit for time-to-first-cardiovascular-event.
We also can’t talk about cardiac myosin inhibitors without talking about safety, and aficamten’s full profile seemed pretty safe, with some common side effects apparent.
- Reversible LVEF reductions (sub 50%) occurred more with aficamten (10.5% vs. 0.8%).
- Serious adverse events were more common with aficamten (20.2% vs 14.7%).
- HF events occurred mostly during aficamten dose titration or before week 12.
Because the individual endpoint differences are modest, investigators also published a global efficacy analysis in Circulation looking at exercise capacity, cardiac structure, biomarkers, diastolic function, and symptoms.
- In that analysis, 53% of aficamten patients showed a clinical response across three or more outcome measures, compared to just 13% on placebo.
These results couldn’t have come at a better time, as Cytokinetics now plans to use the data to submit a supplemental New Drug Application to the FDA in Q4 2026.
- That submission plan comes alongside a Cytokinetics’ lawsuit against BMS over a patent it obtained containing the active ingredient in aficamten.
The Takeaway
The full picture of ACACIA-HCM confirms that aficamten has more than a puncher’s chance of becoming the first approved drug for nHCM. Bearing that in mind, the secondary endpoints suggest it’ll be a symptom management approach rather than a cure.
