aficamten (CK-274) / Cytokinetics, Bayer, Sanofi - LARVOL DELTA

The CHMP adopted a positive opinion for Myqorzo (aficamten) for the treatment of adults with obstructive hypertrophic cardiomyopathy, a disease in which the muscle in the main pumping chamber of the heart becomes thickened or enlarged, which can block the flow of blood from the heart to the rest of the body. (European Medicines Agency)

CHMP • Obstructive Hypertrophic Cardiomyopathy

Therapeutic Sequencing in Obstructive Hypertrophic Cardiomyopathy: Seeing the Forest Through the Trees. (PubMed, JACC Heart Fail) - No abstract available

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

Aficamten in Obstructive Hypertrophic Cardiomyopathy: A Multidomain, Patient-Level Analysis of the MAPLE-HCM Trial. (PubMed, J Am Coll Cardiol) - P3 | "In patients with symptomatic oHCM, aficamten monotherapy led to superior and rapid treatment benefits across several clinically relevant outcome measures of disease burden compared with metoprolol. These observations support the emerging role of aficamten as monotherapy for oHCM. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM [MAPLE-HCM]; NCT05767346)."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Efficacy and Safety of Aficamten in Children and Adolescents With Obstructive Hypertrophic Cardiomyopathy: Study Design and Rationale of CEDAR-HCM. (PubMed, Circ Heart Fail) - P2/3, P3 | "Results of CEDAR-HCM will provide insight into the safety and efficacy of aficamten in adolescents and in children as young as 6 years of age. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06412666."

Clinical • Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pediatrics

CYP450 activity, drug interactions and genetic polymorphisms: clinical relevance for the new selective cardiac myosin inhibitors. (PubMed, Expert Opin Drug Saf) - "Two new cardiac myosin inhibitors (CMIs), mavacamten and aficamten, reduce the intensity of myosin - actin cross-bridge formation and could treat causes of HCM. However, CYP3A4 can influence the disposition of these CMIs and other drugs, as CYP3A4 is subjected to induction and inhibition, and modulation by inflammatory factors. Therefore, multi-drug interactions due to changes in the metabolic clearances of CMIs are expected in HCM patients with other chronic conditions and polypharmacy."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • CYP2C19 • CYP2C9 • CYP3A4

Catastrophic apical ballooning in an obstructive hypertrophic cardiomyopathy patient treated with mavacamten: case report. (PubMed, Eur Heart J Case Rep) - "Recently, myosin inhibitors (mavacamten, aficamten) have been introduced to specifically counteract LVOTO. To the best of our knowledge, this is the first report describing apical ballooning in oHCM during mavacamten treatment. The causal role of mavacamten in this acute heart failure case is unproven, yet-being a cardiac myosin inhibitor and considering the shock recurrence after initial recovery-plausible."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pulmonary Disease

Danicamtiv, a Novel Direct Enhancer of Cardiac Myosin Motor Function, Improves Cardiac Performance and Output in the setting of Myosin Dysfunction: In vitro and In vivo Evidence. (AHA 2025) - "The responses to DANI were assessed under control conditions and in the setting of myosin dysfunction, resulting from either DCM-pathogenic MYH7 mutations (in recombinant cS1), or via pharmacological cardiac myosin inhibition (MYHi: CK-274 or CK-586) in vitro/in vivo. DANI enhanced the ATPase cycling rate of cS1 in wild-type and five DCM MYH7 variants (AC50, WT: 3.8 µM vs. F764L: 3.2µM). Danicamtiv can directly improve the function of cardiac myosin in the setting of (genetic or induced) dysfunction, increasing the number of myosin heads forming productive cross-bridges, thus increasing/restoring force generation and systolic performance in vivo. These observations, if confirmed in humans, could suggest a potential novel mechanism-based targeted therapy for a subset of patients with DCM"

Late-breaking abstract • Preclinical • Cardiomyopathy • Cardiovascular • CNS Disorders • Depression • Psychiatry • MYH7 • TTN

CEDAR-HCM: A Study to Evaluate the Effect of Aficamten in Pediatric Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM). (clinicaltrials.gov) - P2/3 | N=55 | Recruiting | Sponsor: Cytokinetics | N=40 ➔ 55

Enrollment change • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pediatrics

Effect of Aficamten in Women Compared with Men with Obstructive Hypertrophic Cardiomyopathy in SEQUOIA-HCM. (PubMed, Circ Heart Fail) - " Women enrolled in SEQUOIA-HCM were older with worse baseline health status, higher NT-proBNP, and higher LVOT gradients compared to men. Despite these differences, both men and women derived significant benefits in the primary and secondary end points following treatment with aficamten."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Effect of Aficamten versus Metoprolol Monotherapy on Biomarkers in Obstructive Hypertrophic Cardiomyopathy: The MAPLE-HCM Trial (AHA 2025) - P3 | "MAPLE-HCM (NCT05767346) compared aficamten vs metoprolol succinate as monotherapy/first-line treatment on peak oxygen uptake (pVO2), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), and echocardiographic measures in symptomatic oHCM.Methods/Approach: Differences in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) were studied in MAPLE-HCM. As monotherapy for oHCM, aficamten significantly reduced NT-proBNP and hs-cTnI compared with metoprolol as monotherapy. Reduction in NT-proBNP concentrations correlated significantly with improved exercise capacity, LVOT-G, and health status. These results provide insights regarding the mechanism of clinical benefit of aficamten compared to metoprolol in MAPLE-HCM."

Biomarker • Monotherapy • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • TNNI3

Clinical Responses to Aficamten Monotherapy Compared with Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy Outcomes and Disease Burden: MAPLE-HCM Responder Analysis (AHA 2025) - P3 | "Patients treated with aficamten were more frequently complete or partial responders (78% vs 3%; p<0.001), whereas those treated with metoprolol were more frequently non- or limited responders (97% vs 20%; p<0.001) (Figure 1).ConclusionsIn symptomatic oHCM patients, treatment with aficamten was associated with superior treatment effect across several clinically relevant outcome measures compared with metoprolol. These observations support the emerging role for aficamten as monotherapy for oHCM."

Clinical • Monotherapy • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Effect of Aficamten vs Metoprolol on Patient-Reported Health Status in Obstructive Hypertrophic Cardiomyopathy (AHA 2025) - P3 | "Aficamten improves the health status of patients with symptomatic oHCM significantly more than metoprolol, supporting its potential use as first-line treatment in oHCM."

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Sanofi has brought to the China International Import Expo two new cardiovascular therapies through partnerships with Chinese partners, highlighting the French pharmaceutical giant's local strategy focused on partnership-driven innovation. (Yicai Global) - "The global debuts of aficamten for hypertrophic cardiomyopathy and plozasiran for familial chylomicronemia syndrome and severe hypertriglyceridemia address critical gaps in China's cardiovascular disease treatment landscape."

Commercial • Cardiomyopathy • Familial Chylomicronemia Syndrome

Continued enrolling patients in CEDAR-HCM (Clinical Evaluation of Dosing with Aficamten to Reduce Obstruction in a Pediatric Population in HCM), a clinical trial of aficamten in a pediatric population with symptomatic obstructive HCM. (The Manila Times) - "We expect to continue patient enrollment of the adolescent cohort into 2026."

Enrollment status • Obstructive Hypertrophic Cardiomyopathy

Advanced the ongoing clinical trials program for aficamten: (The Manila Times) - "Advanced European commercial readiness activities, including preparing Health Technology Assessment (HTA) dossiers for key EU markets and ensuring launch readiness for potential approval in Germany in 1H 2026."

Launch Europe • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Continued conduct of ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), a pivotal Phase 3 clinical trial of aficamten in patients with non-obstructive HCM. (The Manila Times) - "Completed enrollment in the Japan cohort of ACACIA-HCM. We expect to share topline results of the primary cohort (excluding Japan) in Q2 2026."

P3 data: top line • Trial status • Non-obstructive Hypertrophic Cardiomyopathy

aficamten (cardiac myosin inhibitor) (The Manila Times) - "Continued to support the review of the New Drug Application (NDA) for aficamten for the treatment of patients with obstructive hypertrophic cardiomyopathy (HCM) by the U.S. Food and Drug Administration (FDA) ahead of the Prescription Drug User Fee Act (PDUFA) action date of December 26, 2025; Submitted responses to the Day 120 List of Questions from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) with respect to the ongoing review of the Marketing Authorization Application...We expect a potential EMA decision regarding the MAA in 1H 2026; Continued to support the review of the NDA for aficamten for obstructive HCM by the Center for Drug Evaluation (CDE) in China."

China filing • EMA approval • PDUFA • Obstructive Hypertrophic Cardiomyopathy

Myosin modulator Aficamten inhibits force in cardiac muscle by altering myosin's biochemical activity without changing thick filament structure (AHA 2025) - "We used a combination of biochemical and biomechanical assays to show that Aficamten inhibits myosin ATPase without appreciably altering myosin structure. This is different from Mavacamten that strongly affects both."

Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

Effect of Aficamten in Women Compared with Men with Obstructive Hypertrophic Cardiomyopathy (AHA 2025) - "Women had similar geometric mean proportional reduction in NT-proBNP (women: 0.16 [0.13 to 0.21]; men: 0.22 [0.18 to 0.27], P-interaction = 0.10).ConclusionsWomen enrolled in SEQUOIA-HCM were older with worse baseline health status, higher NT-proBNP, higher LV filling pressure, and higher LVOT gradients compared to men. Despite these differences, both men and women derived similar benefits in the primary and most secondary endpoints following treatment with aficamten, with a greater improvement in health status in women."

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Chronic Aficamten Treatment Results in Sustained Favorable Cardiac Remodeling in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: Insights From the FOREST-HCM Trial (AHA 2025) - P2/3, P3 | "Treatment with aficamten for 48 weeks in patients with oHCM resulted in significant improvement in important measures of cardiac structure and function, with continued benefit after 24 weeks and no meaningful adverse effects on LV systolic function, indicating sustained and favorable long-term cardiac remodeling."

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Aficamten is safe and effective in oHCM with comorbidities obesity, hypertension, and diabetes: a SEQUOIA-HCM sub-study (AHA 2025) - P3 | "The incidence of serious adverse events and left ventricular ejection fraction <50% were similar across subgroups, including when grouped by treatment arm.Conclusion(s): Comorbidities, particularly obesity and hypertension, are common in patients with oHCM. Aficamten treatment showed consistent clinical efficacy regardless of comorbidity status, supporting its use across a broad patient population."

Atrial Fibrillation • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity • Obstructive Hypertrophic Cardiomyopathy • Type 1 Diabetes Mellitus

Improvement in Echocardiographic Measures of Diastolic Function Reflects Improved Exercise Performance in Obstructive Hypertrophic Cardiomyopathy: Insights From the SEQUOIA-HCM Trial (AHA 2025) - P3 | "Aficamten treatment resulted in the improvement of measures of diastolic function, including E/e', along with evidence of LA remodeling, both of which were associated with enhanced exercise capacity. These findings highlight diastolic dysfunction as a key pathophysiologic feature in oHCM and identify modifiable metrics that may aid in monitoring therapeutic response."

Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Long-term Impact of Aficamten on Patient-Reported Outcome Measures in Obstructive Hypertrophic Cardiomyopathy: Results From FOREST-HCM (AHA 2025) - P2/3 | "Aficamten led to significant and sustained improvements in PROs in patients with oHCM. The improvement was seen across all symptom domains, particularly QoL, and correlated with important clinical measures of disease severity."

Clinical • Patient reported outcomes • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

ACACIA-HCM: Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM (clinicaltrials.gov) - P3 | N=500 | Active, not recruiting | Sponsor: Cytokinetics | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy

Efficacy of aficamten in patients with obstructive hypertrophic cardiomyopathy and mild symptoms: results from the SEQUOIA-HCM trial. (PubMed, Eur Heart J) - P3 | "Patients with oHCM and mild symptoms treated with aficamten achieved significant improvement across a range of clinically relevant outcomes and generally similar to patients with more advanced symptoms. Less severely symptomatic patients could be considered for aficamten treatment."

Clinical • Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy