CYTOKINETICS INC

Current report

Although ACACIA-HCM met both of its dual primary endpoints, the FDA and other regulatory agencies may not find the results of ACACIA-HCM sufficient to support approval of aficamten for the treatment of nHCM, and any such approval may be delayed, limited or denied.

Current report

In August 2026, we announced the primary results from ACACIA-HCM, our pivotal Phase 3 clinical trial of aficamten in patients with symptomatic nHCM. ACACIA-HCM met both of its dual primary endpoints, demonstrating statistically significant improvements from baseline to Week 36 compared to placebo in both KCCQ Clinical Summary Score and maximal exercise performance (pVO2), and statistically significant improvements compared to placebo were also observed in its key secondary endpoints. Based on these results, we plan to submit a supplemental NDA to the FDA for aficamten for the treatment of adult patients with symptomatic nHCM in the fourth quarter of 2026. However, there can be no assurance that the FDA or any other regulatory agency will find the results of ACACIA-HCM sufficient to support approval of aficamten for the treatment of nHCM.

Current report

Achieving statistical significance on the primary and secondary endpoints of a clinical trial does not by itself establish that a drug is effective for regulatory purposes. The FDA and other regulatory agencies will evaluate the totality of the clinical data from ACACIA-HCM, including the magnitude, durability and clinical relevance of the observed treatment effects, the consistency of those effects across endpoints and patient subgroups, and the adverse events and overall safety profile of aficamten in the nHCM population, in determining whether aficamten is efficacious for the treatment of nHCM and whether its benefits outweigh its risks in this patient population. Regulatory agencies’ interpretations of what constitutes a minimally important clinical difference in functional endpoints such as KCCQ Clinical Summary Score and pVO2 can be subjective because there is no universally established standard, and because there is no approved therapy for nHCM, there is no established benchmark against which the magnitude of the benefit observed in ACACIA-HCM can be measured. Accordingly, the FDA may conclude that the improvements observed in ACACIA-HCM, although statistically significant, are not clinically meaningful or are not of a sufficient magnitude to demonstrate that aficamten is efficacious for the treatment of nHCM, or may otherwise disagree with our interpretation of the data.

Current report

In addition, the nHCM patient population presents distinct physiological differences from the oHCM population, and drug candidates with mechanisms of action similar to aficamten have failed in nHCM. For example, Camzyos (mavacamten), a cardiac myosin inhibitor commercialized by Bristol-Myers Squibb Company, failed to meet its dual primary endpoints in ODYSSEY-HCM, a Phase 3 clinical trial assessing its efficacy for the treatment of nHCM. Regulatory agencies may consider the results of ACACIA-HCM in light of these prior results and the broader body of evidence regarding cardiac myosin inhibitors in nHCM. Furthermore, in ACACIA-HCM, left ventricular ejection fraction below 50% occurred more frequently in participants taking aficamten than in participants taking placebo, and certain participants taking aficamten experienced serious adverse events of heart failure. Regulatory agencies may weigh these safety findings against the observed efficacy in assessing the benefit-risk profile of aficamten in nHCM and, even if they approve aficamten for the treatment of nHCM, may require additional data or analyses, impose labeling restrictions, dose titration or monitoring requirements or modifications to the existing REMS program, or approve a narrower indication than the one we seek.

Current report

If the FDA or other regulatory agencies do not accept our supplemental NDA for filing, do not find the results of ACACIA-HCM sufficient to support approval, require additional clinical trials or data, or delay or limit any approval, we would be unable to commercialize aficamten for the treatment of nHCM on the timeline we anticipate, or at all. Any such outcome could materially and adversely affect our business, financial condition, results of operations and prospects, the market price of our common stock and our ability to achieve the objectives of our corporate strategy, which contemplates regulatory approvals of aficamten in nHCM in multiple geographies.