Aficamten

Trial Demonstrates Superiority of Aficamten to Standard of Care Beta Blocker in Improving Peak Exercise Capacity in Patients with Obstructive Hypertrophic Cardiomyopathy May 13, 2025 -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced positive topline results from MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), a Phase 3 clinical trial comparing aficamten as monotherapy to the standard of care beta blocker metoprolol as monotherapy in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). 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. The safety and tolerability profile of aficamten was favorable in comparison to metoprolol in MAPLE-HCM. The full results from MAPLE-HCM will be presented at an upcoming medical conference. “These results represent the first evidence that aficamten may be used as monotherapy to deliver clinically meaningful improvements in people living with obstructive hypertrophic cardiomyopathy,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “Importantly, the results from MAPLE-HCM provide important context to the benefit of this potential new medicine compared to the current standard of care. We are grateful to the investigators, site personnel and patients who participated in MAPLE-HCM, and look forward to presenting the full results at an upcoming medical meeting.” MAPLE-HCM was a Phase 3, multi-center, randomized, double-blind active-comparator clinical trial of aficamten compared to metoprolol in patients with symptomatic obstructive HCM. The primary endpoint was the change in peak oxygen uptake (pVO2) from baseline to Week 24 measured by cardiopulmonary exercise testing (CPET). Secondary endpoints include the change from baseline to Week 24 in Kansas City Cardiomyopathy Questionnaire (KCCQ) score, the proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class, and changes in left ventricular mass index (LVMI), left atrial volume index (LAVI), post-Valsalva left ventricular outflow tract gradient (LVOT-G) and NT-proBNP. MAPLE-HCM enrolled 175 patients, randomized on a 1:1 basis to receive aficamten or metoprolol as monotherapy in a double-blind, double dummy fashion. Randomization was stratified by CPET exercise modality (treadmill or bicycle) and recently diagnosed versus chronic obstructive HCM. At screening, patients enrolled in MAPLE-HCM had a resting LVOT-G ≥30 mmHg and/or post-Valsalva LVOT-G ≥50 mmHg in addition to left ventricular ejection fraction (LVEF) ≥ 60%, respiratory exchange ratio (RER) ≥ 1.05 and pVO2 aficamten or metoprolol based on echocardiographic guidance as well as a matching placebo for the alternate therapy. 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 and as may translate into next-in-class potential in clinical development. 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 compared to placebo in SEQUOIA-HCM, a positive pivotal Phase 3 clinical trial demonstrating improvements in functional capacity, LVOT gradients, and heart failure symptoms in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) and from the National Medical Products Administration (NMPA) in China. Aficamten is currently under regulatory review in the U.S by the FDA 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. 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 obstructive HCM; and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. Cytokinetics is a specialty cardiovascular biopharmaceutical company, building on its over 25 years of pioneering scientific innovations in muscle biology to advance 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. Cytokinetics is also developing omecamtiv mecarbil, a cardiac myosin activator, in patients with heart failure with severely reduced ejection fraction (HFrEF), CK-586, 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. References: Xu, D., Lutz, J., & Divanji, P., et al. (2024, March). Drug–Drug Interaction Study to Evaluate the Effect of Strong CYP3A Inhibition and P450 Induction on the Pharmacokinetics of Aficamten and the Effect of Aficamten on P-Glycoprotein in Healthy Participants. Poster session presented at the American Society for Clinical Pharmacology & Therapeutics Meeting, Colorado Springs, CO. CVrg: Heart Failure 2020-2029, p 44; Maron et al. 2013 DOI: 10.1016/S0140-6736(12)60397-3; Maron et al 2018 10.1056/NEJMra1710575 Symphony 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 The content above comes from the network. if any infringement, please contact us to modify.

Today, a brief rundown of news involving Bluebird bio and Affimed, as well as updates from Cytokinetics, BridgeBio Pharma and Acelyrin that you may have missed.Carlyle and SK Capital Partners, two investment firms attempting to buy Bluebird bio, have amended their offer to give Bluebird shareholders a choice of payouts. Holders of Bluebird stock can either receive $3 per share plus rights to $6.84 more if a certain sales milestone is achieved Carlyle and SK Capitals original bid or $5 per share. Shareholders previously had a deadline of May 12 to tender their stock to the original deal, but now have until May 29 to do so. Bluebirds board is in favor of accepting Carlyle and SK Capitals offer, warning investors in a statement Wednesday that, absent a deal, the company is at significant risk of default. Ned PagliaruloCancer drug developer Affimed has filed for insolvency, warning investors Tuesday that there is substantial doubt the company can sustain itself. As a result of the filing, Affimed shares will be suspended from trading on the Nasdaq stock exchange beginning May 20. The company has been talking with potential investors and partners about deals or other ways in which it might raise capital, but has so far been unsuccessful. Affimed, which has three drugs in clinical testing, last reported cash holdings of 24 million euros as of Sept. 30, 2024. Ned PagliaruloCytokinetics on Tuesday said its experimental drug aficamten outperformed beta blockers in a Phase 3 study of people with obstructive hypertrophic cardiomyopathy. U.S. regulators are already reviewing aficamtens use in the inherited heart condition, with an approval decision now expected by late December after a recent delay. The latest results, though generally expected by investors, could help boost its case with physicians and insurers, wrote RBC Capital Markets analyst Brian Abrahams. If approved, aficamten would compete for market share with Bristol Myers Squibbs Camzyos, which booked $602 million in sales last year. Ben FidlerBridgeBio Pharma has begun dosing patients in a first-of-its-kind Phase 3 trial testing whether its drug, Attruby, can prevent or delay the onset of transthyretin amyloidosis in people more likely to inherit it. The trial, ACT-EARLY, will evaluate Attruby as a prophylactic treatment in carriers of a disease-causing variant of the TTR gene thats implicated in the hereditary form of the condition. Attruby is one of three marketed drugs that can slow progression of a type of transthyretin amyloidosis that affects the heart. No medicines have been proven to prevent the disease, however. Ben FidlerShareholders in Acelyrin and Alumis voted Tuesday to combine the two biotechnology companies, ending a twisting merger saga that featured an unsolicited bid from an entity controlled by Tang Capital and a push from Trium Capital to force Acelyrin to liquidate its assets and return cash to its stockholders. Since announcing the planned combination, Alumis has tweaked the terms of the deal, saying its shareholders would own 52% of the new company, while Acelyrins would hold 48%. The merger is now set to close in the second quarter of 2025. Gwendolyn Wu '