What Is Aficamten?
Aficamten is an investigational drug currently being studied for various forms of hypertrophic cardiomyopathy (HCM). HCM is a condition where the heart muscle becomes abnormally thick, making it harder for the heart to pump blood effectively. Aficamten is administered as an oral tablet and is being investigated for its potential to improve heart function and symptoms in patients with this condition.
Development of Aficamten is primarily sponsored by Cytokinetics, with one trial also sponsored by Corxel Pharmaceuticals. While the specific mechanism of action is not detailed in the provided trial descriptions, clinical trials involving Aficamten began on 2021-04-19, with the latest trial starting on 2024-05-14. A total of seven trials have been conducted or are ongoing, including two recruiting trials and four completed trials. These studies have collectively enrolled approximately 1,996 participants to date.
Uses and Conditions Under Study
Aficamten is primarily being investigated for its potential to treat hypertrophic cardiomyopathy (HCM), a condition characterized by thickening of the heart muscle. This thickening can make it difficult for the heart to pump blood efficiently, leading to symptoms like shortness of breath, chest pain, and fatigue.
The majority of studies focus on obstructive hypertrophic cardiomyopathy (oHCM), where the thickened heart muscle blocks blood flow from the heart. Aficamten is being studied to see if it can reduce this obstruction and improve symptoms. A total of four trials specifically investigate Aficamten for obstructive hypertrophic cardiomyopathy, including one trial for symptomatic obstructive hypertrophic cardiomyopathy.
Beyond obstructive forms, Aficamten is also being studied for broader symptomatic hypertrophic cardiomyopathy (HCM), which includes both obstructive and non-obstructive types. One trial specifically addresses symptomatic non-obstructive hypertrophic cardiomyopathy, and another focuses on symptomatic HCM generally. These trials aim to determine if Aficamten can alleviate symptoms and improve quality of life across the spectrum of HCM.
In addition to therapeutic studies, Aficamten has also been investigated in healthy participants. These studies, typically involving one trial, are crucial for understanding how the drug is absorbed, distributed, metabolized, and excreted in the body, as well as for assessing its safety profile before widespread use in patients.
Furthermore, one trial is exploring Aficamten in the pediatric population. This indicates an effort to understand the drug's effects and appropriate dosing in children, who may respond differently to medications than adults.
Dosing
Aficamten is administered as an oral tablet, typically taken once daily. The specific strengths and dosing regimens have varied across the clinical trials as researchers work to identify the most effective and safest dose for patients.
Investigational doses of Aficamten have ranged from 5 mg to 20 mg in some studies. Other trials have explored higher doses in specific dose-finding cohorts, including Aficamten 50 mg, Aficamten 75 mg, and Aficamten 100 mg. These higher doses were likely part of initial studies to determine the maximum tolerated dose and dose-response relationship.
Some studies have also included comparator arms, such as metoprolol succinate up to 200 mg, or moxifloxacin 400 mg, to evaluate Aficamten's effects against existing treatments or for specific safety assessments like cardiac rhythm (TQT study). While a trial in the pediatric population is underway, specific pediatric dosing information is not detailed in the provided trial descriptions.
Side Effects
In a clinical trial involving 142 patients, the most common side effects experienced by individuals taking Aficamten were headache and hypertension. Headache occurred in 7.7% of patients taking Aficamten, compared to 7.1% on placebo. Hypertension was reported by 7.7% of patients on Aficamten, while 2.1% of patients on placebo experienced it.
Other side effects reported in the trial included:
- Palpitations: 7.0% of patients taking Aficamten experienced palpitations, compared to 2.9% on placebo.
- Upper respiratory tract infection: 6.3% of patients on Aficamten, compared to 8.6% on placebo.
- Dyspnoea (shortness of breath): 5.6% of patients on Aficamten, compared to 5.7% on placebo.
- Fatigue: 2.1% of patients on Aficamten, compared to 5.0% on placebo.
- Angina pectoris (chest pain): 2.1% of patients on Aficamten, compared to 5.0% on placebo.
Clinical Trial Results
Clinical trials have evaluated the effectiveness of Aficamten in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
In a Phase 3 trial (NCT05186818), Aficamten demonstrated improvements in patient symptoms, functional capacity, and heart obstruction compared to placebo over 24 weeks. The trial included 142 participants in the Aficamten arm.
Symptom Improvement and Quality of Life:
- Patients taking Aficamten experienced a significant improvement in their symptoms and physical limitations, as measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). At Week 12, patients on Aficamten showed an 11.1-point improvement from baseline, compared to a 4.0-point improvement for those on placebo. By Week 24, this improvement was 11.6 points for Aficamten patients, versus 4.3 points for placebo.
- The proportion of patients who experienced at least a one-class improvement in their New York Heart Association (NYHA) Functional Class, which assesses the severity of heart failure symptoms, was higher with Aficamten. At Week 24, 58.5% of patients (83 out of 142) on Aficamten showed improvement, compared to 23.9% of patients (34 out of 142) on placebo.
Reduction in Heart Obstruction:
- Aficamten significantly reduced the Valsalva Left Ventricular Outflow Tract Gradient (LVOT-G), a measure of obstruction in the heart. At Week 24, patients on Aficamten had an average reduction of 48 mmHg from baseline, while patients on placebo showed an average increase of 2 mmHg.
- A greater proportion of patients achieved a Valsalva LVOT-G of less than 30 mmHg, indicating reduced obstruction. At Week 24, 49.3% of patients (70 out of 142) on Aficamten reached this goal, compared to 3.5% of patients (5 out of 142) on placebo.
Improved Exercise Capacity:
- Patients treated with Aficamten showed an improvement in their peak oxygen consumption (pVO2), a measure of exercise capacity. At Week 24, patients on Aficamten had an average increase of 1.76 mL/kg/min from baseline, compared to an average increase of 0.02 mL/kg/min for those on placebo.
- The total workload during exercise increased by 13.4 watts for patients on Aficamten, compared to 1.2 watts for those on placebo, at Week 24.
Currently Recruiting Trials
Clinical trials are essential for developing new treatments and understanding how they work. If you or a loved one are living with hypertrophic cardiomyopathy (HCM), you may be interested in learning about ongoing studies for Aficamten. These trials aim to gather more information about the potential benefits and safety of this investigational medication.
One active study, identified as NCT06412666, is evaluating Aficamten in pediatric patients. This Phase 2/3 study, sponsored by Cytokinetics, focuses on children with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Researchers are assessing the efficacy, safety, and how the body processes Aficamten in this younger population. The trial aims to enroll approximately 55 pediatric patients to understand its potential impact.
Another important study, NCT04848506, is an open-label extension study designed to collect long-term safety and tolerability data for Aficamten in adults with HCM. This Phase 2/3 trial, also sponsored by Cytokinetics, allows participants to continue receiving Aficamten at dosages up to 20 mg. With an enrollment target of 900 adults, this study is crucial for understanding the medication's effects over an extended period.
Where to Participate
Aficamten clinical trials have a broad reach across the United States, offering opportunities for participation in many communities. Currently, there are 75 study sites located in 51 cities across 33 states. This wide network helps ensure that more patients can access these important research opportunities.
The eligibility criteria for participating in these trials generally include individuals aged 12 to 85 years, with all genders welcome. It is important to note that these studies are not seeking healthy volunteers; participants must have symptomatic hypertrophic cardiomyopathy. Children are eligible for specific trials, such as the pediatric study mentioned previously.
Top locations with multiple study sites include:
- New York, New York
- Los Angeles, California
- Ann Arbor, Michigan
- Nashville, Tennessee
- Portland, Oregon
- San Francisco, California
- Dallas, Texas
- Houston, Texas
- Boston, Massachusetts
- Phoenix, Arizona
Development Timeline
The journey of Aficamten began with its first clinical trial initiated on April 19, 2021. Initially, the development pipeline explored conditions such as IBS-C and hyperphosphatemia, with Corxel Pharmaceuticals sponsoring one early study. However, the focus soon shifted and expanded.
The primary sponsor, Cytokinetics, has driven the majority of the research, sponsoring six of the seven total trials. The development program quickly broadened to include healthy participants before concentrating on various forms of hypertrophic cardiomyopathy (HCM). This expansion included studies for symptomatic hypertrophic cardiomyopathy, symptomatic non-obstructive hypertrophic cardiomyopathy, symptomatic obstructive hypertrophic cardiomyopathy, and more recently, pediatric populations.
Aficamten's development has progressed through different phases, including one Phase 1 study, two Phase 2/3 studies, and four Phase 3 studies, reflecting a robust and advancing research program. To date, a total of seven trials have been conducted or are ongoing, with a combined enrollment of 1,996 participants. The latest trial was initiated on May 14, 2024, demonstrating ongoing commitment to understanding and developing Aficamten.