Cytokinetics Begins Phase 1 Study of Aficamten in Healthy Japanese Volunteers

June 17, 2024 – Cytokinetics, Inc. has begun dosing participants in a Phase 1 clinical study to evaluate the pharmacokinetics, safety, and tolerability of aficamten in healthy Japanese and Caucasian individuals. Fady I. Malik, M.D., Ph.D., Executive Vice President of Research & Development, emphasized the importance of this study for potentially gaining approval for aficamten in Japan, alongside ongoing global clinical developments and regulatory preparations in the U.S. and Europe.

The Phase 1 trial is designed as a double-blind, randomized, placebo-controlled study. It aims to assess the pharmacokinetics of aficamten through both single ascending doses and multiple doses among 70 healthy participants from Japanese and Caucasian backgrounds. The secondary aim is to evaluate the drug's safety and tolerability. Participants are divided into four cohorts: three cohorts will receive single ascending doses, and one cohort will receive multiple doses. Each cohort will consist of 10 Japanese and 10 Caucasian participants, randomized in an 8:2 ratio to receive aficamten or a placebo. The doses for the single ascending cohorts are set at 5 mg, 10 mg, and 20 mg, moving forward sequentially based on safety evaluations. The final cohort will see participants receiving 5 mg daily for 14 days.

Aficamten is a selective cardiac myosin inhibitor developed to manage hypertrophic cardiomyopathy (HCM) by reducing myocardial hypercontractility. This small molecule was discovered through an extensive chemical optimization program and works by decreasing the number of active actin-myosin cross bridges during cardiac cycles. This action reduces myocardial contractility by binding selectively to a unique allosteric site on cardiac myosin, thus preventing myosin from entering a force-producing state.

The development program for aficamten aims to improve exercise capacity and alleviate symptoms in HCM patients, while also examining its long-term effects on cardiac structure and function. Aficamten has shown promise in the SEQUOIA-HCM pivotal Phase 3 trial, targeting symptomatic obstructive HCM patients. It has also received Breakthrough Therapy Designation from both the U.S. FDA and China's NMPA for treating symptomatic obstructive HCM. Cytokinetics plans to submit a New Drug Application (NDA) to the FDA in Q3 2024 and a Marketing Authorization Application (MAA) to the EMA in Q4 2024.

Further evaluation of aficamten is ongoing in several other trials: MAPLE-HCM compares aficamten as monotherapy to metoprolol in patients with obstructive HCM; ACACIA-HCM investigates its effects in non-obstructive HCM patients; CEDAR-HCM studies its use in a pediatric population with obstructive HCM; and FOREST-HCM is an open-label extension study in HCM patients.

Cytokinetics is a biopharmaceutical company focusing on innovative treatments for cardiovascular diseases where muscle performance is impaired. The company continues to advance its pipeline of muscle activators and inhibitors, including omecamtiv mecarbil for heart failure and CK-586 for HFpEF, and is also developing CK-136 for the potential treatment of various heart failure types. Cytokinetics remains at the forefront of muscle biology research, aiming to address diseases characterized by muscle dysfunction and weakness.

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