Robert Blum and Fady Malik, M.D., Ph.D, have been with Cytokinetics since its inception nearly three decades ago. Monday afternoon, as they sat in a conference room and discussed the overwhelmingly successful trial results for Myqorzo (aficamten), it was with equal parts excitement and humility.
By nailing both primary endpoints in the phase 3 ACACIA-HCM study, Cytokinetics is on its way to becoming the first company to gain approval for a drug to treat non-obstructive hypertrophic cardiomyopathy (nHCM).
Myqorzo was endorsed by the FDA in December of last year to treat the obstructive form of the condition, bringing with it blockbuster potential. The opportunity that presents itself with nHCM would double the potential patient population for the cardiac myosin inhibitor, according to claims data collected by Cytokinetics.
With the trial results, Cytokinetics' share price increased by 21% on Monday morning.
While scoring its first approval in Myqorzo was a significant milestone five months ago, CEO Blum and R&D chief Malik sounded particularly moved that Cytokinetics has become the first company to provide positive trial results in the indication and are on the verge of delivering medicine for the first time for those with nHCM.
“There’s a very robust, consistent effect here that is—for those of us in this business—one of those things that you aspire towards, but you rarely achieve and that’s incredibly gratifying,” Blum said of the study results in an interview with Fierce.
In the trial, Myqorzo provided statistically significant improvements from baseline to Week 36 compared to placebo. The primary endpoints were measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ), which is filled out by patients, and the maximal exercise performance standard.
The improvement on the KCCQ was “robust and consistent” throughout the treatment period for those on Myqorzo, the company said. As for the exercise test, participants were assessed by measuring peak oxygen uptake. Malik compared the uptake improvement that was observed in the study as equal to “weeks of hard training,” provided by Myqorzo.
Cytokinetics did not report secondary endpoints, but said statistically significant improvements were observed consistently across all measures.
Blum said that the company will discuss the results with the FDA as soon as possible.
At a steering committee meeting on Monday, in which the results were discussed, members tossed out terms like “transformational, terrific, home run,” Blum said.
“There’s never been a study that has shown positive results in this population,” Blum said. “In some ways, we were going for it in the design and conduct of this study, without a lot of benchmarks and reference standards, but we believed in the drug candidate and how we could best approach designing a proper study—and it worked.”
In its obstructive hypertrophic cardiomyopathy indication, Cytokinetics is competing with Bristol Myers Squibb’s cardiac myosin inhibitor Camzyos, which was approved in 2022 and generated $1.07 billion in sales last year.
BMS came up short last year in the Odyssey trial of Camzyos in nHCM, but the company is giving it another shot in the indication with plans to initiate a new study which it announced last week during its first quarter presentation.
"We have learned a lot from Odyssey," chief medical officer Cristian Massacesi said during the quarterly call. "We know better who the patients are and which diseases they are affected by that can benefit most from a myosin inhibitor like Camzyos."
BMS's failure in the indication makes Cytokinetics’ success with a drug with the same mechanism of action that much more noteworthy.
“Not every biopharma company is as rooted in novelty biology and science as we are. We’re forging a path,” Blum said. “It’s taken us over 25 years to be able to enable this kind of innovation.”