At two recent meetings, South San Francisco biotech company Cytokinetics presented encouraging data on its experimental drug for hypertrophic cardiomyopathy, aficamten (formerly known as CYK-274).
Results from the REDWOOD-HCM open label extension study were presented as a Late Breaking Presentation at the European Society of Cardiology Heart Failure Congress. These results showed that after 6 months of treatment with aficamten, patients improved by one or more New York Heart Association class, with a corresponding improvement in symptoms. Additionally, there were significant reductions seen in left ventricular outflow tract gradients. According to the presentation, the drug is safe and well tolerated, and only a small decreases in left ventricular ejection fraction was seen in a small number of trial participants. Improvements were also seen in cardiac biomarkers NTpro-BNP and troponin, which are measured via blood test.
Also, data was presented at the American Society of Echocardiography 33rd Annual Scientific Sessions which showed that after 10 weeks of treatment with aficamten, a significant reduction in left atrial volume index was noted, as well as a what appeared to be a lessening of left ventricular hypertrophy. Improvements in ventricular relaxation and filling, as well as in mitral valve dynamics were also observed.
If you would like to learn more about aficamten, here are some past entries on HCMBeat:
2 Companies Testing Drugs for HCM
HCM Clinical Trials – the Latest News
The Future of HCM Care
Positive Signs from REDWOOD-HCM
Cytokinetic’s Drug Aficamten & Upcoming HCM Summit – Interview with Dr. Martin Maron
Aficamten Gets “Breakthrough Drug” Status from FDA
More on Aficamten & Mavacamten from ACC 2022
Cytokinetics Announces its Phase 2 Clinical Trial – “Redwood-HCM”
Cytokinetics Moves Forward with HCM Drug Trial
Cytokinetics Announces Positive Results from REDWOOD-HCM Phase 2 Clinical Trial
Dr. Iacopo Olivotto and a team of Italian researchers conducted a recent multi-center trial of the late sodium channel blocker ranolazine. The results of the trial showed that the drug failed to improve functional capacity, diastolic function, quality of life or brain natriuretic peptide (BNP) levels in 80 non-obstructive HCM patients.
Nevertheless, the researchers found that ranolazine is a very safe drug which may still be useful in the treatment of HCM by reducing arrhythmias and improving angina.
A companion editorial by Dr. Perry Elliot from the U.K. shed light on the difficulties inherent in designing clinical trials for HCM. Dr. Elliot noted that Restyle HCM was the third unsuccessful attempt at finding a new drug for HCM in the past year since a study on eleclazine, a drug with similar properties, and another for the drug perhexilene were both halted last year due to lack of efficacy.
Regardless, Dr. Elliot stated that increasing worldwide collaboration between HCM centers and expanding knowledge of certain sub-types of HCM treatable with specifically targeted therapies substantially improve the outlook for upcoming HCM drug trials.
MyoKardia’s experimental drug MYK-461, currently in Stage 2 trials for humans, has now been shown to eliminate left ventricular obstruction in five cats with HCM. It has already been shown to inhibit traits of HCM in mice.
Addressing these findings, Associate Professor Joshua Stern, chief of the Cardiology Service at the University of California, Davis, veterinary hospital, stated:
“There has been little to no progress in advancing the treatment of HCM in humans or animals for many years,” Stern said. “This study brings new hope for cats and people.”
Based on these positive results, U.C.Davis is hoping to conduct a clinical trial of MYK-461 to determine whether it could become the standard of care for cats with HCM.
The full text of the article published in Plos One can be found here.
Eleclazine: The Liberty HCM Trial
It appears to be the end of the road for the Gilead drug eleclazine, a late sodium channel inhibitor previously known as GS-6615. Eleclazine, with properties similar to the anti-angina drug ranolazine (which was approved by the FDA in 2006), was the subject of a recently terminated HCM clinical trial known as Liberty-HCM. The HCM eleclazine study focused on whether the drug would improve symptoms and exercise capacity in patients with HCM by increasing their peak oxygen uptake, resulting in improved VO2 max readings on exercise testing. The HCM study began enrolling patients in February 2015. Data collection had been scheduled to continue through June 2017. Continue reading “End of the Road for Eleclazine and Liberty HCM Study”
Heart Metabolics announced today that its drug, Perhexiline, has moved into Phase 2b trials. The drug is intended for those patients with HCM and moderate to severe heart failure with preserved left ventricular function. Results of the Phase 2a study found the drug improved exercise capacity and quality of life in patients taking the drug.
To learn more about the staging of clinical drug trials and how they work, click here.