Cytokinetics Teases Q2 Phase 3 ACACIA-HCM Readout as Myqorzo Launch Gains Traction at Citi Conference

Cytokinetics (NASDAQ:CYTK) used its presentation at Citi’s Life Sciences Conference to highlight the recent U.S. approval of its first drug, Myqorzo, and to preview an upcoming Phase 3 readout in non-obstructive hypertrophic cardiomyopathy (NHCM) that management described as a major near-term catalyst.

ACACIA-HCM Phase 3 readout expected in Q2

CEO Robert Blum said the company expects clinical trial results in the second quarter from ACACIA-HCM, a pivotal Phase 3 study evaluating Myqorzo in NHCM. Myqorzo is already approved in obstructive HCM (OHCM), and Blum framed the NHCM opportunity as roughly comparable in size to the obstructive market. Citing claims data analyses, he said NHCM represents about 50% of the total diagnosed and symptomatic hypertrophic cardiomyopathy population in the U.S.

Blum also said Cytokinetics believes there are at least 100,000 OHCM patients in the U.S. who could be eligible for treatment with Myqorzo, and suggested there is a “similar number” of NHCM patients potentially available to treat. If ACACIA is positive and leads to FDA approval in NHCM, he said the company could potentially be alone in that segment, while still competing in the existing OHCM market.

As context, Blum noted that Bristol Myers Squibb’s Camzyos, a cardiac myosin inhibitor, generated over $1 billion in U.S. and European sales last year. He added that Cytokinetics is entering an OHCM category that is already established, and said the company believes more than 80% of the OHCM population eligible for treatment remains untreated with a cardiac myosin inhibitor.

Why Cytokinetics thinks cardiac myosin inhibition can work in NHCM

Chief Medical Officer Fady Malik described both the similarities and differences between obstructive and non-obstructive disease. He said both forms share common underlying pathology, including thickening of the heart, diastolic dysfunction, excessive cross-bridge formation, and hypercontractility. Malik also pointed to changes in biomarkers and echocardiographic measures that have been observed with treatment.

Malik highlighted NT-proBNP, a marker associated with cardiac wall stress and filling pressures, noting that levels fall in both conditions. In OHCM, he said decreases in NT-proBNP at two weeks in Cytokinetics’ Phase 3 trial were the most predictive biomarker of improved exercise function at 24 weeks. He added that improvements in relaxation measured on echocardiography are also seen in NHCM.

However, Malik cautioned that NHCM lacks the left ventricular outflow tract gradient that is reduced in obstructive disease, which could “mute” treatment effects on exercise performance. He said patient-reported outcomes may capture broader aspects of patient wellbeing beyond maximum exercise performance.

Trial design lessons from ODYSSEY-HCM

Management contrasted its approach with Bristol Myers Squibb’s ODYSSEY-HCM trial of Camzyos in NHCM, which Blum characterized as a “near miss” and Malik said did not achieve statistical significance despite signs that peak VO₂ and the Kansas City Cardiomyopathy Questionnaire (KCCQ) trended positively.

Malik said ODYSSEY-HCM had an unusually large placebo effect on KCCQ. He also described dosing-related challenges in that program, including an inability to pilot dosing effectively in Phase 2, and said about 20% of patients in ODYSSEY-HCM interrupted treatment due to low ejection fraction—interruptions he described as leading to reduced consistency of exposure.

Blum emphasized that beyond trial design, trial execution can determine outcomes. He said Cytokinetics’ team has conducted HCM trials since 2019 and highlighted continuity of personnel, training of trial sites on endpoint assessments, monitoring for outliers, screening oversight, and the use of a core lab. He referenced multiple Cytokinetics studies—REDWOOD-HCM, SEQUOIA-HCM, MAPLE-HCM, FOREST-HCM, CEDAR-HCM, and ACACIA—as evidence of experience conducting trials as designed.

ACACIA dosing and endpoint timing

Malik described ACACIA’s titration protocol as straightforward. Patients start at 5 milligrams, with dosing decisions every two weeks based on echocardiographic ejection fraction:

• If ejection fraction is above 60%, dose is increased.
• If ejection fraction is between 50% and 60%, dose is maintained.
• If ejection fraction is below 50%, dose is reduced.

He said patients can reach target dose within six weeks, and the primary endpoint is measured at 36 weeks—implying roughly 30 weeks of exposure at target dose. Malik contrasted this with ODYSSEY-HCM, where he said mavacamten dose changes were considered after three months and required a higher ejection fraction threshold (65%) for increases.

Malik also described Cytokinetics’ Phase 2 work in NHCM, in which about 40 patients were studied at 5, 10, and 15 milligram doses using a titration algorithm that only increased dose when ejection fraction was at least 60%. He said the strategy produced no treatment interruptions, no “big drops” in ejection fraction, and only a small number of down-titrations, supporting the approach used in Phase 3.

Early Myqorzo launch signs and positioning

Turning to commercialization, Blum said Myqorzo was launched in January, with product in channel in the third week of the month. He and Malik discussed attributes they said were engineered into aficamten, including a shallow exposure-response relationship, reduced susceptibility to drug interactions, and an onset/offset profile that allows dose down-titration without needing to interrupt therapy.

Blum said Myqorzo’s FDA label and associated REMS program provide flexibility around echocardiography timing during up-titration and do not require drug-drug interaction monitoring, which he said could reduce burden for physicians, patients, and pharmacists.

On early launch metrics, Blum said more than 700 cardiologists registered and trained in the REMS program within a couple of weeks, and that “many” began writing prescriptions immediately. He said prescriptions were processed and, through the patient hub, some patients were dispensed and reimbursed within days, particularly among commercially insured patients. He added that the company has a free drug program and expects some lag between prescription and reimbursement, but said early velocity measures were encouraging. Cytokinetics plans to begin reporting patient numbers and prescribing breadth and depth starting with its first-quarter earnings call in the second quarter.

Blum also said the company is engaging both high-volume and broader prescriber segments, noting it has engaged with more than 90% of an estimated group of roughly 700 cardiologists who account for the majority of current Camzyos prescriptions. He added that early prescribing is also emerging in areas without prior Camzyos use, which he said could indicate potential for broader community uptake over time.

In closing remarks, Malik briefly discussed Cytokinetics’ second cardiac myosin inhibitor, ulacamten, in Phase 2 for heart failure with preserved ejection fraction (HFpEF). He described HFpEF patients as having thickened hearts, heart failure symptoms, and elevated NT-proBNP, with some features similar to NHCM, and said success in ACACIA could help inform application of the mechanism in adjacent populations. He also said ulacamten binds at a different location on myosin than aficamten, which he suggested may translate into different pharmacology.

About Cytokinetics (NASDAQ:CYTK)

Cytokinetics, Inc is a late‐stage biopharmaceutical company focused on the discovery and development of novel small‐molecule therapeutics that modulate muscle function. Founded in 1998 and headquartered in South San Francisco, California, the company applies its proprietary insights in muscle biology to address diseases characterized by impaired muscle performance. Its research spans both cardiac and skeletal muscle targets, aiming to deliver innovative medicines for conditions with significant unmet medical need.

The company’s most advanced program, omecamtiv mecarbil, is being evaluated for the treatment of heart failure by enhancing cardiac muscle contractility.