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Interim results from the REDWOOD-HCM OLE trial are providing clinicians with insight into the impact of aficamten on symptom improvement and quality of life in patients with obstructive hypertrophic cardiomyopathy.
Presented at the Heart Failure Society of America (HFSA) 2022 annual scientific meeting, data from the analysis suggest use of aficamten was associated with significant and sustained reduction in left ventricular outflow gradient (LVOT-G) as well as improvements in heart failure symptoms and reductions in NT-proBNP and hs-cTnL.
Discovered from the optimization of indoline compound 1, excitement for surrounding the next-generation cardiac myosin inhibitor, aficamten, has reached a fever pitch with the approval of mavacamten for obstructive hypertrophic cardiomyopathy in April 2022. At HFSA, aficamten drew attention with the current study an additional poster outlining the design of the phase 3 SEQUOIA-HCM trial, which launched in February 2022.
A phase 2 dose-finding trial, the interim analysis of REDWOOD-HCM OLE, which was presented by Ahmad Masri, MD, director of the Oregon Health and Science University Hypertrophic Cardiomyopathy Center, provides the latest insights into the effects of aficamten. The outcomes of interest for the interim analysis were changes in LVOT-G, NYHA function class, and cardiac biomarkers among the 38 individuals receiving aficamten in the trial. During his presentation, Masri pointed out more than 50% of patients who had reached 24 weeks of treatment with aficamten were using aficamten 15 mg by week 24 of the trial, with more than 75% using a dosage of 10 mg or greater.
Upon analysis, results indicated 61% of patients receiving aficamten had a 1 class improvement in NYHA class at 24 weeks, with 17% experiencing an improvement of 2 classes. Of note, 22% of patients experienced no change in NYHA class from baseline to week 24, but no patient experienced a worsening of NYHA class from baseline to week 24. Masri also pointed out there were no events of a left ventricular ejection fraction (LVEF) dropping below 50% were observed during the open-label extension trial. When assessing cardiac biomarkers, results indicated mean levels of NT-proBNP were reduced by 70% (P <.0001) occurred from baseline to week 12 and a reduction of 20% (P=.002) was observed for mean hs-cTnL during the same time period.
In a late-breaking oral presentation at HFSA 2022, a new analysis of REDWOOD-HCM OLE evaluates patients’ self-reported health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and comparing baseline values to those collected at Week 12 and Week 24. In qaa release from Cytokinetics, the company noted that, at weeks 12 and 24 of the trial, the mean change in KCCQ-OSS from baseline was 16.5 (SD, 16.7; P <.0001) and 17.6 (SD, 24.7; P=.0015). Further, the release pointed out an improvement of 5 points or more on the KCCQ-OSS was observed among 72.7% at week 12 and 72.0% at week 24. When assessing improvements of 20 points or more, results indicated this level of improvement was observed among 36.4% at week 12 and 40.0% at week 24, according to the release.
“These new data suggest that improvements in cardiac function associated with treatment with aficamten translate to patients reporting an overall improvement in their symptoms – particularly in their quality of life – which is of critical importance to patients with HCM who face a substantial symptom burden that impacts their daily lives.” said Fady I. Malik, MD, PhD, executive vice president of Research & Development at Cytokinetic, in a statement from Cytokinetics. “As REDWOOD-HCM OLE continues, aficamten is also under study in SEQUOIA-HCM, the phase 3 registrational clinical trial in patients with obstructive HCM.”
This study, “Efficacy And Safety Of 'Aficamten' In Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From The Randomized Evaluation Of Dosing With Ck-3773274 In Hypertrophic Cardiomyopathy Open Label Extension Study,” was presented at HFSA 2022.