Cytokinetics, a San Francisco biotech firm, is hoping that its experimental HCM drug, aficamten, will quickly be a competitor to Bristol Myers Squibb’s first-in-class myosin inhibitor Camzyos (mavacamten). Aficamten is an oral cardiac myosin inhibitor which, like Camzyos, treats HCM by decreasing the the extreme variety of interactions between cardiac myosin proteins.
An earlier Section 2 examine known as Redwood-HCM established the protection of the drug. The optimistic outcomes of Redwood-HCM led to the Section 3 examine entitled Sequoia – HCM.
Topline outcomes of Sequoia-HCM had been offered in late December of 2023, whereas main outcomes and knowledge from the examine had been offered on Could 13 at tthe European Society of Cardiology Coronary heart Congress assembly held in Lisbon, Portugal. The whole paper was revealed within the New England Journal of Drugs on Could 13, 2024.
The Research: The examine enrolled 282 sufferers with obstructive HCM. Half had been assigned to the drug whereas half took a placebo drug as an alternative. The entire interval of remark for the examine was 28 weeks. Sufferers enrolled within the examine took aficamten for twenty-four weeks, adopted by a 4 week interval for washout of the drug. Sufferers in each teams had been allowed to remain on background therapies together with beta blockers, calcium channel blockers, and disopyramide.
Major Endpoint: The first endpoint of the examine, in addition to all 10 secondary endpoints, had been met with statistically significant outcomes. The first endpoint confirmed an enchancment to train capability, quantified by a rise in peak oxygen uptake (pVO2) as measured by cardiopulmonary train testing (CPET) on a treadmill or bike by 1.8 ml/kg/min over a interval of 24 weeks.
The examine outcomes additionally met a number of secondary endpoints together with:
Subjective Enchancment in Signs: Sufferers scores confirmed a 7 level improve on the Kansas Metropolis Cardiomyopathy Questionnaire. It is a questionnaire that has been validated for measuring coronary heart failure signs over time by asking people repeated questions on how they’re feeling.
Enchancment in purposeful capability: 34% of sufferers experiencing ≥1 class enchancment as measured by New York Coronary heart Affiliation (NYHA) class (which is decided by the medical crew after remark and questioning).
Septal Discount Remedy Eligibility: Nearly the entire sufferers who certified for septal discount remedy in the beginning of the examine now not certified for invasive septal discount therapies on the finish (i.e. septal myectomy and septal alcohol ablation).
Security: Aficamten was discovered to be protected and effectively tolerated. There was no must interrupt therapy for coronary heart failure when a affected person’s ejection fraction fell beneath 50%. If a affected person’s ejection fraction (EF) did fall beneath 50%, the EF recovered both spontaneously or when the aficamten dosage was decreased.
No variations in response had been seen in responders based mostly on age, intercourse or utilization of background drug therapies.
When will Aficamten be out there to sufferers?
Cytokinetics expects to file for regulatory approval in each the U.S. and Europe by the top of the 2024. They hope that they’ll be capable of deliver the drug to market by the top of 2025, relying on the timing and outcomes of the regulatory course of. The prescribing info and any restrictions surrounding use (i.e. the need and frequency of repeat echocardiograms and REMS program, each that are mandated for Camzyos) may also be decided by regulators.
For extra about aficamten see these previous blogs on HCMBeat:
Is Aficamten the Blockbuster Drug Cytokinetics is Hoping For?
Cytokinetics Teases Upcoming Section 3 Aficamten Trial in nHCM
Promising Information about Aficamten Offered at Conferences
Aficamten Updates from Cytokinetics
Extra on Aficamten & Mavacamten from ACC 2022
Aficamten Will get “Breakthrough Drug” Standing from FDA
Cytokinetic’s Drug Aficamten & Upcoming HCM Summit – Interview with Dr. Martin Maron