Shares of Cytokinetics (NASDAQ:CYTK) jumped 28% on Tuesday after the company disclosed topline results from ACACIA-HCM, the pivotal Phase 3 study evaluating aficamten in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (HCM).
The trial met both of its dual primary endpoints, showing statistically significant gains from baseline to Week 36 versus placebo in two core measures: the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and maximal exercise performance measured by peak oxygen consumption (pVO2). The reported difference in KCCQ-CSS between aficamten and placebo was 3.0 points with a p-value of 0.021. For pVO2, the difference was 0.67 mL/kg/min with a p-value of 0.003.
ACACIA-HCM randomized and treated 516 participants in a 1:1 allocation to receive either aficamten or placebo. Beyond the primary endpoints, the study produced statistically significant improvements across key secondary endpoints. One highlighted secondary result was the greater proportion of participants who experienced at least one class improvement in New York Heart Association (NYHA) functional class.
"Patients with non-obstructive HCM have no therapies approved to treat the underlying hypercontractility associated with the disease," said Fady I. Malik, Cytokinetics’ Executive Vice President of Research & Development. "We hope that will change with ACACIA-HCM which is the first clinical trial to demonstrate statistically significant improvements in exercise capacity and symptom burden in patients with non-obstructive HCM."
On safety, the company reported no new safety signals from the study. The proportion of participants completing the planned dosing regimen was similar across treatment arms - 88.4% for those receiving aficamten compared with 90.3% for placebo.
Aficamten is already approved for symptomatic obstructive HCM in the U.S., China and the European Union under the brand name MYQORZO. Cytokinetics stated it plans to present more detailed data at an upcoming medical meeting and to discuss the full dataset with the U.S. Food and Drug Administration and other regulatory authorities.
The topline announcement fueled immediate investor interest, reflecting the market's focus on the study's positive primary and secondary outcomes as well as the absence of new safety concerns. The company will next move to share full results with clinicians and regulators, steps that the company indicated are part of its plan following these topline findings.
Key points
- Cytokinetics reported that ACACIA-HCM met both primary endpoints: KCCQ-CSS (difference 3.0 points, p=0.021) and pVO2 (difference 0.67 mL/kg/min, p=0.003).
- The trial enrolled and treated 516 participants randomized 1:1 to aficamten or placebo and showed significant improvements on key secondary endpoints, including NYHA class improvements.
- No new safety signals were observed and dosing completion rates were comparable between arms - 88.4% for aficamten versus 90.3% for placebo.
Risks and uncertainties
- Regulatory review and discussions with the FDA and other authorities remain to occur - the company plans to present detailed results and engage with regulators, and outcomes of those interactions are not yet known.
- While no new safety signals emerged in the topline results, continued review of the full dataset will be necessary to confirm the safety profile.
- The company noted that there are currently no approved therapies for underlying hypercontractility in non-obstructive HCM - the path from positive trial results to approved treatment involves additional regulatory and presentation steps.