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Last update 29 Oct 2025

Aficamten

Last update 29 Oct 2025

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BAY-3723113, CK 274, CK 3773274

+ [2]

Target

Cardiac myosin

Action

inhibitors

Mechanism

Cardiac myosin inhibitors

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Hypertrophic obstructive cardiomyopathyHypertrophic Cardiomyopathy without ObstructionHeart failure with normal ejection fraction

Inactive Indication-

Originator Organization

Cytokinetics, Inc.

Active Organization

Thermo Fisher Scientific, Inc.

Cytokinetics, Inc.

Bayer AG

+ [1]

Inactive Organization-

License Organization

Royalty Pharma Plc

Corxel Pharmaceuticals (Shanghai) Co., Ltd

Sanofi

+ [2]

Drug Highest PhaseNDA/BLA

First Approval Date-

RegulationBreakthrough Therapy (United States), Orphan Drug (United States), Priority Review (China), Breakthrough Therapy (China)

Structure/Sequence

Molecular FormulaC18H19N5O2

InChIKeyIOVAZWDIRCRMTM-OAHLLOKOSA-N

CAS Registry2364554-48-1

Clinical Trials associated with Aficamten

NCT07023341

/ RecruitingPhase 3

A Phase 3, Open Label, Single Arm Study to Evaluate Efficacy, Safety and Tolerability of Aficamten in Adult Japanese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Researchers are looking for a better way to treat Japanese people who have symptomatic obstructive hypertrophic cardiomyopathy (symptomatic oHCM).
Obstructive hypertrophic cardiomyopathy (oHCM) is a type of heart disease where the heart muscles become thicker than normal due to over contraction. This thickening makes it harder than normal due to over contraction. This thickening makes it harder for the heart to pump blood out to the rest of the body. In symptomatic oHCM people with the condition experience symptoms like shortness of breath, chest pain, fainting, high blood pressure and irregular heartbeats.
The study treatment aficamten, also called BAY3723113, is under development to treat symptomatic oHCM. It aims to reduce the activity of cardiac myosin, a protein that helps heart muscles to contract, and thereby preventing over contraction and muscle thickening.
Although treatment options are available for symptomatic oHCM, there is still need for other treatment options that help target the root cause of the condition. In this study, researchers want to understand about the effects and long-term safety of aficamten in Japanese people with symptomatic oHCM.
The main purpose of the study is to learn how well aficamten works in Japanese with symptomatic oCHM.
For this, the researchers will check how participant's heart blood flow changes after 6 months of treatment. They do this by measuring the pressure needed for blood to leave the heart using a test called the left ventricular outflow tract (LVOT) gradient and a special breathing technique called Valsava maneuver.
Researchers will also look for:
* the number of participants who will have at least 1 level improvement on a scale doctors use to assess the effect of heart problems on daily activities after 3 and 6 months of treatment
* the change in the impact of heart problems on participant's daily lives based on their feedback on a questionnaire called Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) after 3 and 6 months of treatment.
This study will have 2 treatment periods: main treatment period and long-term treatment period. During the main treatment period, participants will take aficamten tablets once daily by mouth for up to 6 months. After completing this period, the participants who can join the long-term treatment period will continue taking aficamten until the drug becomes commercially available in Japan or the study ends.
Each participant will be in the study as long as they benefit from the treatment.
Participants will visit the study site:
* once before the treatment starts
* 9 times with a gap of 2 to 4 weeks between the visits during treatment under the main treatment period, and in the long-term treatment period, participants will visit almost every 3 months until the treatment ends.
* then 2 more times with a gap of 1 month between the visits after the treatment ends.
During the study, the study doctors and their team will:
* check participant's health by performing tests such as blood and urine tests, and checking heart health using an electrocardiogram (ECG) and echocardiogram (ECHO)
* ask the participants questions about how they are feeling and what adverse events are they having
An adverse event is any medical problem that a participant has during a study. Study doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatment. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study.
If the participant benefits from the treatment, treatment with aficamten after the end of the study might be possible.

Start Date30 Jun 2025

Sponsor / Collaborator

Bayer AG

NCT06412666

/ RecruitingPhase 2/3

A Phase 2/3 Multicenter, Randomized, Double-Blind, Placebo-Controlled and Open-Label Extension Trial to Evaluate the Efficacy and Safety of Aficamten in a Pediatric Population With Symptomatic Obstructive Hypertrophic Cardiomyopathy

The purpose of this study is to evaluate the efficacy, safety and PK of aficamten in a pediatric population with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).

Start Date29 May 2024

Sponsor / Collaborator

Cytokinetics, Inc.

NCT06116968

/ RecruitingPhase 3

An Open-Label Study of Aficamten for Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy

This is an open-label extension study of China cohort in the phase 3 study (CY 6031) of aficamten for the treatment of obstructive HCM (oHCM) to collect long-term safety and tolerability data, including assessments of cardiac function and steady-state Pharmacokinetics (PK) during chronic dosing with aficamten.

Start Date14 Nov 2023

Sponsor / Collaborator-

100 Clinical Results associated with Aficamten

100 Translational Medicine associated with Aficamten

100 Patents (Medical) associated with Aficamten

Literatures (Medical) associated with Aficamten

01 Dec 2025·Journal of cardiovascular imaging

Cardiac myosin inhibitors in hypertrophic cardiomyopathy

Review

Author: Lim, Jaehyun ; Kim, Hyung-Kwan

Abstract:

Mavacamten, the first selective and reversible cardiac myosin inhibitor (CMI), has been introduced to the clinical arena for the treatment of obstructive hypertrophic cardiomyopathy (HCM). By reducing excessive actin-myosin cross-bridging, this agent decreases myocardial contractility and alleviates the dynamic left ventricular outflow tract (LVOT) obstruction in obstructive HCM. In the EXPLORER-HCM trial, mavacamten significantly improved exercise capacity, symptoms, and LVOT pressure gradients, while the VALOR-HCM trial proved it can obviate the need for septal reduction therapy in patients who were deemed to be candidates for septal reduction therapy. Notably, long-term data (MAVA-LTE study) has demonstrated sustained benefits up to 180 weeks, with < 10% experiencing transient reductions in left ventricular ejection fraction < 50% and only 1.3% of permanent discontinuation rate. Aficamten, a next-generation CMI with a shorter half-life, has also demonstrated comparable efficacy. Reverse remodeling following treatment was noted in both agents. In nonobstructive HCM, preliminary studies (MAVERICK-HCM trial and cohort 4 of REDWOOD-HCM trial) have reported improvements in cardiac serum biomarkers and symptoms. However, the preliminary results from phase 3 trials (ODYSSEY-HCM trial) revealed that primary endpoints were not met in nonobstructive HCM. Regarding safety, both were generally well tolerated. Although an LVEF reduction occurred in some patients, it was reversible with a dose reduction or a short-term drug cessation. These results emphasize careful dosing strategy with regular echocardiographic monitoring. Real-world data have also demonstrated consistent efficacy and safety across varying ethnic groups without new safety signals. CMI is a major advance in HCM management. However, future studies must provide data on hard clinical outcomes, such as heart failure hospitalization or death. Ongoing trials comparing CMI to traditional first-line therapies, such as β-blockers, will clarify their potential role as an initial therapeutic option.

07 Oct 2025·CIRCULATION

Characterization and Application of Novel Exercise Recovery Patterns That Reflect Cardiac Performance: A Substudy of the SEQUOIA-HCM Trial

Article

Author: Kulac, Ian J. ; Owens, Anjali T. ; Malik, Fady I. ; Wohltman, Amy ; Claggett, Brian L. ; Campain, Joseph ; Griskowitz, Catharine ; Prasad, Cheshta ; Kupfer, Stuart ; Moreno, Fabely ; Coats, Caroline J. ; Heitner, Stephen B. ; Newlands, Chloe ; Lee, Matthew M.Y. ; Landsteiner, Isabela ; Malhotra, Rajeev ; Minasian, Alexandra ; Giverts, Ilya ; Maron, Martin S. ; McGinnis, Shaina ; Jacoby, Daniel L. ; Lewis, Gregory D. ; Iskenderian, Nick ; Rupert, Lillian

BACKGROUND::

Post-exercise oxygen uptake recovery (VO 2 Rec) is slow in advanced heart failure. We sought to establish easily derived VO 2 Rec measures and evaluate their cardiospecificity and prognostic relevance in patients with dyspnea on exertion. We further sought to determine VO 2 Rec modifiability proportional to changes in cardiac function with disease-specific treatment of obstructive hypertrophic cardiomyopathy.

METHODS::

VO 2 Rec patterns were evaluated in relation to cardiac performance and the primary outcome of heart failure hospitalization or death in a referral cohort with dyspnea on exertion undergoing cardiopulmonary exercise testing with hemodynamic monitoring (MGH-ExS [Massachusetts General Hospital Exercise Study]). We then investigated longitudinal measures of VO 2 Rec in the pivotal phase 3 randomized controlled trial SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in Hypertrophic Cardiomyopathy) of aficamten versus placebo for 24 weeks in participants with symptomatic obstructive hypertrophic cardiomyopathy. For both cohorts, VO 2 Rec was uniformly measured as time for VO 2 to decline by >0%, 12.5% (VO 2 T 12.5% ), 25%, and 50% of peak VO 2 .

RESULTS::

Among 814 MGH-ExS patients (58±16 years of age, 58% women), those with a longer VO 2 T 12.5% (≥35 versus <35 seconds) demonstrated elevated exercise pulmonary capillary wedge pressure to cardiac output slope ( P <0.0001) with no difference in peripheral oxygen extraction ( P =0.11). For each 15-second increase in VO 2 T 12.5% , the hazard ratio for heart failure hospitalization and all-cause death was 1.54 (95% CI, 1.35–1.76; P <0.001). In SEQUOIA-HCM participants with cardiopulmonary exercise testing at baseline and week 24 (n=263, 59.1±2.9 years of age, 41% women), baseline VO 2 T 12.5% was 45±20 seconds and improved 8 seconds (95% CI, −12 to −5 seconds; P <0.001) with aficamten treatment compared with placebo at 24 weeks. Participants treated with aficamten versus placebo were more likely to improve VO 2 T 12.5% by ≥15 seconds (odds ratio [OR], 3.7 [95% CI, 1.9–6.9]; number needed to treat=4.8). Shortening of VO 2 T 12.5% correlated with reduced NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin I, and left ventricular outflow tract gradient (all P <0.005).

CONCLUSIONS::

This study established VO 2 T 12.5% as a new measure that reflects cardiac performance during exercise and predicted heart failure event-free survival. Furthermore, VO 2 T 12.5% improved proportional to improvements in left ventricular outflow tract gradient and cardiac biomarkers in response to aficamten treatment, a cardiospecific therapy for obstructive hypertrophic cardiomyopathy. The simplicity and physiological relevance of VO 2 T 12.5% support its regular inclusion in cardiopulmonary exercise testing protocols evaluating cardiac function during exercise.

REGISTRATION::

URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05186818.

01 Oct 2025·PROTEIN SCIENCE

Understanding hypertrophic cardiomyopathy and its regulation by myosin drugs

Article

Author: Warshel, Arieh ; Halder, Ritaban

Abstract:

Hypertrophic cardiomyopathy (HCM) is an inherited form of heart disease, caused by specific mutations, many of which are encoded by the β‐cardiac myosin (MYH7) protein. This work provides molecular insight into the effect of an HCM‐causing mutation, R190T of β‐cardiac myosin. The Arginine190 (R190) resides near the active site of the cardiac myosin and its alteration by a threonine (T190) residue leads to cardiac abnormalities related to the fatal HCM. Since the mutations lead to change in the function of the myosin, we focused on our previous finding that the motion and its directionality are determined by the rate‐determining barrier, which in the current case is the phosphate release step. Our study of the change of the phosphate release barrier used several approaches, including all‐atom umbrella sampling simulations, renormalization simulations, binding energy and stability analysis as well as structural and multiple sequence analysis. Our free energy calculations of the barrier for the rate‐determining phosphate release step reproduced the observed effect. Furthermore, we show that three key myosin drugs, aficamten, mavacamten, and omecamtiv, modulate the phosphate release barrier of the faulty myosin, and by this means it could repair the defects of the HCM mutant associated with fast phosphate release. In exploring the reasons for the effects of the mutations and the drugs, we conclude that the R190T mutation leads to the destabilization of the prepowerstroke (PPS) state of cardiac myosin. Such destabilization triggers rapid phosphate release from cardiac myosin. Since phosphate release is the rate‐determining step of β‐cardiac myosin, such alteration of the phosphate release barrier of the R190T mutant is a crucial functional factor. Our study demonstrates the importance of using multiscale approaches for the revelation of key mechanisms of HCM disease. Furthermore, we provide further evidence of the crucial role of the rate‐determining barrier in establishing the overall function of the myosin cycle.

242

News (Medical) associated with Aficamten

29 Sep 2025

·www.globenewswire.com

Cytokinetics Presents New Data Related to Aficamten at the HFSA Annual Scientific Meeting 2025

Additional Data from MAPLE-HCM Show Aficamten Significantly Improves Measures of Maximaland Submaximal Exercise Capacity and Recovery Compared to Metoprolol 96-Week Analyses from FOREST-HCM SupportLong-Term Efficacy and Tolerability of Aficamten in Patients with Non-Obstructive HCM SOUTH SAN FRANCISCO, Calif., Sept. 29, 2025 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that additional data related to aficamten were presented in a Late Breaking Clinical Research session at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025 in Minneapolis, MN. The first presentation was a pre-specified analysis of the effect of aficamten compared to metoprolol on exercise performance in obstructive HCM (oHCM) in MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), and the second was an analysis from FOREST-HCM (Follow-up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM) on the efficacy and tolerability of long-term treatment of aficamten in patients with non-obstructive hypertrophic cardiomyopathy (nHCM), simultaneously published in the Journal of Cardiac Failure.1 “The additional data from MAPLE-HCM expands our understanding of aficamten across several measures of exercise performance, with effects observed not only in peak exercise capacity, but also in submaximal exercise and recovery from exercise,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “Additionally, the long-term data from FOREST-HCM in patients with nHCM show sustained improvements in both patient symptom burden and cardiac biomarkers associated with aficamten. Most patients achieved the highest doses available without any early treatment discontinuations, giving us confidence in the dosing strategy and the potential of aficamten to benefit patients with nHCM, as is being assessed in the ongoing Phase 3 clinical trial, ACACIA-HCM.” Pre-Specified Analysis of Supplemental Endpoints from MAPLE-HCM Shows Aficamten Improves Measures of Submaximal and Maximal Exercise Performance and Post-Exercise Recovery Compared to Metoprolol Gregory Lewis, M.D., Jeffrey and Mary Ellen Jay Chair and Section Head, Heart Failure Medical Director, Cardiopulmonary Exercise Testing (CPET) Laboratory, Professor of Medicine, Harvard Medical School presented pre-specified supplemental analyses of the impact of treatment with aficamten relative to metoprolol on CPET measures of exercise performance from onset through post-exercise recovery in MAPLE-HCM. The primary result of MAPLE-HCM demonstrated the superiority of aficamten to metoprolol on peak oxygen uptake (pVO2) (change from baseline to Week 24, least squares mean (LSM) treatment difference (SE), +2.3 (0.39) mL/kg/min, p<0.001). In these new analyses, aficamten compared to metoprolol was also shown to nominally significantly improve measures of submaximal exercise performance, including anaerobic threshold, aerobic efficiency (VO2/work), ventilatory efficiency (pre-anaerobic threshold and VE/VCO2 slope), and other key measures of maximal exercise performance, including peak workload, peak heart rate, exercise duration and heart rate reserve (Table 1). Additionally, the speed of VO2 recovery, a sensitive measure of cardiometabolic resilience, increased with aficamten and slowed with metoprolol. A responder analysis showed that any improvement in pVO2 was observed more commonly with aficamten compared to metoprolol, while any worsening was more frequent in the metoprolol group. Table 1Submaximal Exercise Response Variables CPET variableLSM (95% CI)*P-value**Anaerobic threshold, mL+76 (41, 111)<0.001Aerobic efficiency(VO2/work), mL/min/watt+0.8 (0.2, 1.3)0.004Ventilatory efficiency(pre-anaerobic threshold)−1.3 (−2.3, −0.3)0.013Ventilatory efficiency(VE/VCO2 slope)−2.8 (−4.0, −1.5)<0.001Maximal Exercise Response Variables Peak workload, watt+8 (3, 13)0.003Peak heart rate, bpm+28 (24, 32)<0.001Exercise duration, min+0.6 (0.2, 1.0)0.002Heart rate reserve, bpm+12 (8, 16)<0.001* LSM (95% CI) = change from baseline to Week 24 least squares mean treatment difference between aficamten and metoprolol, 95% confidence interval** All p-values are nominal and not controlled for multiple comparisons New Data from FOREST-HCM Support the Efficacy and Tolerability of Long-Term Treatment with Aficamten in Patients with Non-Obstructive HCM Ahmad Masri, M.D., MS, Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University, presented new data related to the safety and long-term use of aficamten in patients with nHCM in FOREST-HCM. These analyses included 34 patients with nHCM who enrolled in FOREST-HCM, the open-label extension study, after completion of Cohort 4 of the Phase 2 clinical trial REDWOOD-HCM. Patients were followed for at least 96 weeks of treatment. At the end of titration (Week 6), 82.4% of patients were on the highest available doses of 15 mg and 20 mg. Through 96 weeks of treatment, there were no early treatment discontinuations and aficamten demonstrated sustained reductions in symptom burden. At Week 96, 27 of the 34 patients (79%) improved by at least one NYHA Functional Class, including 20 (74%) who became asymptomatic (NYHA Functional Class 1). Patients also experienced a mean increase in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) of 11.2 points (±14.3 points). Aficamten also improved cardiac biomarkers, with both NT-proBNP and high-sensitivity cardiac troponin I rapidly declining by Week 12 and remaining low through Week 96. There was a modest reduction in left ventricular ejection fraction (LVEF) from hyperdynamic at baseline to within normal range at Week 12 (-6.2%; p<0.0001). Over the treatment period, four patients had LVEF <50% (5.4 per 100 patient-years) which were reversible after down titration or a short treatment interruption. Only one instance of LVEF <50% was corroborated by the core lab. The efficacy and safety of aficamten in non-obstructive HCM is being investigated in an ongoing Phase 3 clinical trial. About Aficamten Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties.1 Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with HCM. In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state. The development program for aficamten is assessing its potential as a treatment that improves exercise capacity as measured by peak oxygen uptake (pVO2) and relieves symptoms in patients with HCM. Aficamten was evaluated in SEQUOIA-HCM, a positive pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic HCM from the U.S. Food & Drug Administration (FDA) and for the treatment of symptomatic obstructive HCM from the National Medical Products Administration (NMPA) in China. Aficamten is also currently being evaluated in ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM; CEDAR-HCM, a clinical trial of aficamten in a pediatric population with oHCM; and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. Disclaimer This communication contains a summary of new data related to the clinical development of aficamten presented at the HFSA Annual Scientific Meeting 2025. Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. Aficamten is currently under regulatory review in the U.S, where the FDA is reviewing a New Drug Application (NDA) for aficamten with a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2025. Additionally, the European Medicines Agency (EMA) is reviewing a Marketing Authorization Application (MAA) for aficamten, and The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) is reviewing an NDA for aficamten with Priority Review. About Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed, however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed in the U.S.2,3,4 Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn’t impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.5 People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes.6 A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation. About Cytokinetics Cytokinetics is a specialty cardiovascular biopharmaceutical company, building on its over 25 years of pioneering scientific innovations in muscle biology, and advancing a pipeline of potential new medicines for patients suffering from diseases of cardiac muscle dysfunction. Cytokinetics is readying for potential regulatory approvals and commercialization of aficamten, a cardiac myosin inhibitor, following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy (HCM). Aficamten is also being evaluated in additional clinical trials enrolling patients with obstructive and non-obstructive HCM. In addition, Cytokinetics is developing omecamtiv mecarbil, a cardiac myosin activator, in patients with heart failure with severely reduced ejection fraction (HFrEF), ulacamten, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten, for the potential treatment of heart failure with preserved ejection fraction (HFpEF) and CK-089, a fast skeletal muscle troponin activator with potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired skeletal muscle function. For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements relating to any of our clinical trials, statements relating to the potential benefits of aficamten or any of our other drug candidates, or our ability to obtain regulatory approval for aficamten in any jurisdiction by any particular date, if ever. Cytokinetics’ research and development activities; the design, timing, results, significance and utility of preclinical and clinical results; and the properties and potential benefits of Cytokinetics’ other drug candidates. Such statements are based on management’s current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to, potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics’ drug candidates that could slow or prevent clinical development or product approval; Cytokinetics’ drug candidates may have adverse side effects or inadequate therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics’ ability to conduct clinical trials; Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; standards of care may change, rendering Cytokinetics’ drug candidates obsolete; and competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics’ drug candidates and potential drug candidates may target. For further information regarding these and other risks related to Cytokinetics’ business, investors should consult Cytokinetics’ filings with the Securities and Exchange Commission. CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries. Contact:CytokineticsDiane WeiserSenior Vice President, Corporate Affairs(415) 290-7757 References: Masri A, et al. Safety and Efficacy of Aficamten in Patients with Nonobstructive Hypertrophic Cardiomyopathy: A 96-Week Analysis from FOREST-HCM. J Card Fail. 2025Chuang C, Collibee S, Ashcraft L, et al. Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. J Med Chem. 2021;64(19):14142–14152. https://doi.org/10.1021/acs.jmedchem.1c01290CVrg: Heart Failure 2020-2029, p 44; Maron et al. 2013 DOI: 10.1016/S0140-6736(12)60397-3; Maron et al 2018 10.1056/NEJMra1710575Symphony Health 2016-2021 Patient Claims Data DoF;Maron MS, Hellawell JL, Lucove JC, Farzaneh-Far R, Olivotto I. Occurrence of Clinically Diagnosed Hypertrophic Cardiomyopathy in the United States. Am J Cardiol. 2016; 15;117(10):1651-1654.Gersh, B.J., Maron, B.J., Bonow, R.O., Dearani, J.A., Fifer, M.A., Link, M.S., et al. 2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Journal of the American College of Cardiology and Circulation, 58, e212-260.Hong Y, Su WW, Li X. Risk factors of sudden cardiac death in hypertrophic cardiomyopathy. Current Opinion in Cardiology. 2022 Jan 1;37(1):15-21

Clinical ResultPhase 3NDABreakthrough TherapyPhase 2

29 Sep 2025

·www.biospace.com

6 FDA Decisions to Watch For in Q4

iStock, Grandbrothers From more than 30 target action dates in the last three months of the year, BioSpace has narrowed the list to six regulatory decisions that could have far-reaching implications for biopharma and patients. As 2025 enters its home stretch, the FDA is also nearing the end of its calendar. But that doesn’t mean that the industry is in for a quiet year-end—quite the opposite, in fact. In the last three months of 2025, the FDA is set to decide on at least 30 regulatory applications, many of which could help shift the treatment landscape for hard-to-treat diseases or push the boundaries for novel modalities. One upcoming verdict, for instance, could mark another industry first for CAR T therapies, while another could mean the comeback of a previously-pulled cancer drug. Here, BioSpace rounds up six of these most highly anticipated decisions in Q4, looking at the data backing their bids and what their approvals could mean for the industry. After Delay, Regeneron Awaits Two Eylea HD Verdicts Regeneron is looking to boost the pro high-dose Eylea with a move into macular edema after retinal vein occlusion (RVO) and a monthly dosing regimen across all its approved indications. The FDA is currently reviewing these applications and is expected to release its verdict in the fourth quarter. No specific decision date has yet been indicated. The regulator had an initial target action date of Aug. 19, but extended the review period due to issues at a third-party manufacturing site, Regeneron announced earlier that month. The production plant in contention was previously owned by the CDMO giant Catalent, which was acquired by Novo Nordisk’s parent company for $16.5 billion in February 2024 . An FDA report made public in August revealed uncontrolled and unaddressed contaminations at this site, including with bacteria and cat hair. Regeneron has nevertheless reassured investors that aside from these third-party problems, the FDA has not flagged any problems with the submission. “Based on our discussions, we believe that there’s nothing significant left to be done,” CEO Leonard Schleifer said during the company’s Q2 earnings call . “We are expecting, once the resolution of the filling issues has occurred, to receive favorable action, we hope, from the FDA.” To support its application for high-dose Eylea, Regeneron filed data from the Phase III QUASAR study, which demonstrated that the high-dose formulation was non-inferior to the currently approved standard-dose version of Eylea when used to treat patients with macular edema after RVO, according to a readout in December 2024. Adverse events were comparable between the two formulations. High-dose Eylea is currently approved for wet age-related macular degeneration, diabetic macular edema and diabetic retinopathy. GSK’s Blenrep Comeback Bid Nears Moment of Truth By Oct. 23, the FDA is expected to release its decision on GSK’s proposal to bring Blenrep back to the market, this time as a second-line treatment for relapsed/refractory multiple myeloma. Blenrep, an antibody-drug conjugate targeting the CD38 protein, was originally approved in August 2020 under the FDA’s accelerated pathway. But soon after failing its confirmatory Phase III study in November 2022, GSK withdrew the product from the market. Then, last year, GSK started setting the stage for Blenrep’s comeback with data from the Phase III DREAMM-7 trial. A readout in February 2024 demonstrated a significant 59% drop in the risk of death or disease progression in patients treated with Blenrep plus bortezomib and dexamethasone, as compared with a similar regimen using Johnson & Johnson’s Darzalex. Then, in June that same year, the pharma reported findings from another late-stage study, DREAMM-8, touting significantly better progression-free survival for Blenrep versus Takeda’s Velcade. GSK is using these two studies to support its regulatory application for Blenrep, but in July this year, the FDA’s internal reviewers flagged “high rates of ocular toxicity and dose modifications” in both trials. The DREAMM studies also had “limited dose exploration” which in turn highlight the unaddressed need for a “careful evaluation” of Blenrep’s risks in its proposed indications, according to the reviewers. An external advisory committee in July agreed with this assessment and voted 7–1 against Blenrep , finding an unfavorable benefit-risk pro the drug in its proposed indication. “The efficacy data were strong but the toxicity data were also very strong,” panelist Neil Vasan said at the time. Shortly after the vote, the FDA extended Blenrep’s review by three months. BMS’ Breyanzi Could Become First CAR T Therapy for Marginal Zone Lymphoma Bristol Myers Squibb is proposing its CAR T therapy Breyanzi for the treatment of marginal zone lymphoma (MZL), potentially blazing the trail for the therapeutic class in this indication. The FDA has a target decision date of Dec. 5. To support its application, BMS filed findings from the Phase II TRANSCEND FL study, a single-arm, open-label trial that enrolled more than 270 patients with relapsed or refractory follicular lymphoma or MZL. Data presented at the 2025 International Conference on Malignant Lymphoma in June demonstrated a 95.5% overall response rate in patients with MZL, including 62.1% who saw a complete response. The safety pro TRANSCEND FL was consistent with what had previously been established for Breyanzi. Rates of cytokine release syndrome and neurologic complications were “low,” according to BMS, with no grade 4 or 5 cases detected. If it wins the FDA’s blessing, Breyanzi would be the first CAR T therapy indicated for MZL, according to an August 2025 news release from the company. It would also mark the second time that Breyanzi notched a regulatory record: In March 2024, it became the first CAR T to win approval for chronic lymphocytic leukemia and small lymphocytic leukemia in relapsed/refractory patients. Breyanzi works by binding to the CD19 protein, in turn triggering the activation and action of CAR-T cells, as well as the release of pro-inflammatory signals to destroy the target tumor. It is also approved for large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. The drug’s label carries a boxed warning for cytokine release syndrome, neurological toxicities and secondary hematological malignancies. Arrowhead Makes Case for RNAi Therapy in Rare Cholesterol Disease After delivering four firsts for the rare disease space in August, the FDA by Nov. 18 could grant another—this one for Arrowhead Pharmaceuticals’ plozasiran , an RNA interference therapeutic for familial chylomicronemia syndrome (FCS). Afflicting 1 to 2 people per million , FCS is an ultra-rare, heritable disease that manifests as excessively high levels of triglyceride levels, typically reaching over 880 mg/dL, according to Arrowhead . In turn, patients with FCS suffer from cardiometabolic and other complications such as diabetes, hepatic steatosis, abdominal pain and even cognitive problems. There are currently no treatments that can adequately control FCS in the U.S., according to Arrowhead. Arrowhead’s answer to FCS is plozasiran , an investigational therapy that reduces the production of the ApoC3 protein, which is naturally produced in liver cells and serves as a component of triglyceride-rich lipoproteins. ApoC3 prevents the breakdown and clearance of these fatty molecules. By reducing ApoC3 production, plozasiran helps normalize lipid levels in FCS patients. Arrowhead is supporting its application with data from the Phase III PALISADE trial. A readout in November 2024 demonstrated that 25 mg of plozasiran—the proposed commercial dose—led to a roughly 80% reduction in triglyceride levels. In at least half of the treated patients, triglyceride levels stayed below 500 mg/dl, a threshold linked with worse acute pancreatitis risk. Plozasiran treatment also resulted in lower cholesterol levels. Arrowhead is also developing plozasiran for severe hypertriglyceridemia and dyslipidemia. Ascendis Eyes Approval in Rare Bone Growth Disorder Also awaiting a rare disease decision is Ascendis Pharma, which is advancing TransCon CNP, also known as navepegritide, for the treatment of children with achondroplasia. The FDA is set to release its verdict by Nov. 30. Achondroplasia is a rare, genetic disease characterized by dwarfism due to faulty bone development. Ascendis is targeting a specific disease type caused by mutations in the FGFR3 gene, resulting in manifestations in different tissues across the body. Aside from bone problems, patients with this specific type of achondroplasia also suffer from muscular, neurological and cardiorespiratory problems. Around 250,000 people worldwide are affected by this disease, according to Ascendis. TransCon CNP works by providing sustained exposure to the C-type natriuretic peptide, a molecule that helps stimulate bone growth and counter the inhibiting effects of FGFR3 mutations. Through this mechanism, Ascendis contends that its drug candidate could help ease the burden of symptoms and complications in achondroplasia. Ascendis tested the TransCon CNP in ACcomplisH, a randomized, double-blinded and placebo-controlled Phase II study that enrolled 42 patients who received 6 μg, 20 μg or 50 μg of the drug. Results, published in The Lancet in November 2023, showed that patients on TransCon CNP saw significant improvements in annualized growth velocity, alongside other key benefits, such as a stabilized quality of life and better physical functioning. In a June 2025 statement , Ascendis Chief Medical Officer Aimee Shu said the biotech’s clinical development program for TransCon CNP is the “first ever to demonstrate improvements beyond linear growth at 52 weeks compared to placebo.” Cytokinetics Could Challenge BMS in Cardiomyopathy Market Closing out this list is Cytokinetics and its cardio candidate aficamten, which is currently under FDA review for obstructive hypertrophic cardiomyopathy (oHCM). The FDA’s target decision date is Dec. 26. Aficamten blocks the cardiac myosin protein, which plays a role in heart contraction, allowing the oral drug candidate to address a key symptom of oHCM. Data from the Phase III MAPLE-HCM study, presented in August at the 2025 European Society of Cardiology Congress, demonstrated a significant improvement in exercise capacity over metoprolol, a beta-blocker used as standard-of-care in the disease. At the time, analysts at Truist Securities said aficamten’s results position it to be “potentially best-in-class” in oHCM. They called the MAPLE-HCM data “robust,” noting that outperforming metoprolol could help aficamten distinguish itself in the oHCM market. Cytokinetics filed for aficamten’s approval in late 2024, at which time the FDA provided an initial target action date of Sept. 26, 2025 . In May, however, the regulator extended its review by three months to review an additional risk mitigation strategy submission. If approved, aficamten will compete with BMS’s Camzyos, also a cardiac myosin inhibitor that won approval for oHCM in 2022 . The pharma is testing the drug in a non-obstructive form of the heart disease, but a readout in April this year was disappointing : Camzyos was unable to significantly outperform placebo in terms of exercise capacity outcomes, nor did it lead to better physical function.

Clinical ResultPhase 3Drug ApprovalPhase 2Immunotherapy

05 Sep 2025

·www.fiercebiotech.com

Led by ex-HI-Bio CEO, Braveheart pays $65M to challenge BMS for heart disease market

Braveheart Bio has flown below the radar since setting up shop last year. \n Braveheart Bio has waded into the fight for a heart disease market, paying (PDF) $65 million upfront for a rival to Bristol Myers Squibb’s Camzyos and Cytokinetics’ aficamten.Jiangsu Hengrui Pharmaceuticals has facilitated Braveheart’s attempt to insert itself into the emerging rivalry between BMS and Cytokinetics. In return for $32.5 million in cash and the same amount in stock, Braveheart has landed ex-China rights to Hengrui Pharma’s selective myosin inhibitor HRS-1893. The deal includes a $10 million near-term milestone and more than $1 billion in more distant potential paydays.The outlay has secured Braveheart rights to a drug candidate that is in phase 3 development in China. Like Camzyos and aficamten, HRS-1893 is designed to treat obstructive hypertrophic cardiomyopathy by inhibiting myosin. Camzyos and aficamten have improved patients’ oxygen capacity in phase 3 trials. Braveheart has flown below the radar since setting up shop last year. Travis Murdoch, M.D., founded the biotech and serves as its CEO. Murdoch led HI-Bio to a $1.15 billion takeover by Biogen last year. After a stint leading Biogen’s West Coast hub, Murdoch returned to startup life with Braveheart and raised cash from Forbion and OrbiMed to support his plans. Full details of those plans are yet to emerge, but the Hengrui Pharma deal sheds some light on where the startup will direct its energy. Braveheart has ceded a big head start to BMS, which launched Camzyos in 2022, and Cytokinetics, which could receive approval for aficamten this year. While HRS-1893 is in phase 3 in China, development in the West is at an early stage. A phase 1 trial started in Australia in June.Offloading the ex-China rights to HRS-1893 extends a string of deals involving Hengrui Pharma. GSK paid $500 million upfront to enter into a broad deal with the Chinese company in July. The GSK deal arrived months after Merck & Co. paid $200 million upfront for a midphase lipoprotein(a) inhibitor.

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100 Deals associated with Aficamten

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertrophic obstructive cardiomyopathy	NDA/BLA	China	Cytokinetics, Inc.	15 Oct 2024
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	United States	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	China	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Japan	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Argentina	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Australia	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Brazil	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Canada	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Denmark	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	France	Cytokinetics, Inc.	30 Aug 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04848506 (FOREST-HCM, Company_Website) Manual	Phase 2/3	Hypertrophic Cardiomyopathy without Obstruction	34	Aficamten (post-REDWOOD-HCM Cohort 4)	cotjlesxwm(hkzlrxicnt) = ljbydffgmz tlqtspmyjz (edzfyygiki ) View more	Positive	29 Sep 2025
NCT05767346 (MAPLE-HCM, Company_Website) Manual	Phase 3	Hypertrophic obstructive cardiomyopathy	-	Aficamten	jfexgduriq(ybiqxmrwgt) = esbkkkfpgm gjhfpmtist (tkqholeysf ) View more	Superior	29 Sep 2025
				Metoprolol	-
NCT05767346 (MAPLE-HCM, Pubmed \| N Engl J Med) Manual	Phase 3	Hypertrophic obstructive cardiomyopathy	175	Aficamten	clezpandgb(srmpdbehbm) = zqxdgibflr jxtuwofqfo (vzwbuyneop, 0.5 - 1.7)	Superior	11 Sep 2025
				Metoprolol	clezpandgb(srmpdbehbm) = ykdueczpnb jxtuwofqfo (vzwbuyneop, -1.7 to -0.8)
NCT04848506 (FOREST-HCM, Pubmed \| JACC Heart Fail)	Phase 2/3	Hypertrophic obstructive cardiomyopathy	213	Aficamten 5 mg	swvjcqfmcz(vpsiifztjs) = 2 (4.3%) asymptomatic and transient instances of left ventricular ejection fraction <50% (range: 47%-49%), neither resulting in drug discontinuation qfyplorfiq (gbfhrenfkl ) View more	Positive	01 Aug 2025
				Aficamten ≤20 mg
NCT05767346 (MAPLE-HCM, Pubmed \| J Am Coll Cardiol)	Phase 3	Hypertrophic obstructive cardiomyopathy	175	Aficamten 5 to 20 mg	qtugzdxnje(kdhqfzecdm) = ngwheeqjjh jbcbfegbeh (rkswixbaaj ) View more	Positive	01 Aug 2025
				Metoprolol 50 to 200 mg	-
NCT05767346 (MAPLE-HCM, GlobeNewswire \| NEWS) Manual	Phase 3	Hypertrophic obstructive cardiomyopathy	-	Aficamten	pwxfrsynxf(fxozpwkukt) = MAPLE-HCM met its primary endpoint, demonstrating a statistically significant improvement in peak oxygen uptake (pVO2) from baseline to Week 24 for aficamten compared to metoprolol. lvwymvpxpp (vpwbveeayr ) Met	Positive	13 May 2025
				Metoprolol
NCT05186818 (SEQUOIA-HCM, GlobeNewswire) Manual	Phase 3	Cardiomyopathy, Hypertrophic	-	Aficamten	uuyamaturs(lwotsfwier) = yyawvzrmww bojzzusene (xfmskescks, 3.1) View more	Positive	16 Nov 2024
				Placebo	uuyamaturs(lwotsfwier) = butianuhav bojzzusene (xfmskescks, 2.7) View more
NCT05186818 (SEQUOIA-HCM, Pubmed \| J Am Coll Cardiol)	Phase 3	Hypertrophic obstructive cardiomyopathy	282	Aficamten	jjqjzdtuki(ubrknwbhwr) = wifsazpvtb dovtemipdd (btuqumsias, -25 to -6) View more	Positive	01 Nov 2024
NCT05186818 (SEQUOIA-HCM, Pubmed \| J Am Coll Cardiol)	Phase 3	Hypertrophic obstructive cardiomyopathy N-terminal pro-B-type natriuretic peptide (NT-proBNP)	282	Aficamten	jktfytzosk(mvuhtkujuc) = sudzuoloqo wwoegaangq (uukhohiesl ) View more	Positive	01 Nov 2024
NCT05186818 (SEQUOIA-HCM, Pubmed \| J Am Coll Cardiol)	Phase 3	Hypertrophic obstructive cardiomyopathy N-terminal pro-B-type natriuretic peptide	-	Aficamten	xhdrvmskpo(tlhvcfqyfv) = vhcuogcpkf hbfynhapvn (bwjikrcili ) View more	Positive	01 Nov 2024
				Placebo	xhdrvmskpo(tlhvcfqyfv) = vqbhmasspc hbfynhapvn (bwjikrcili ) View more

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