Ahmad Masri, MD, MS, is the director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University. 

Ahmad Masri, MD, MS

New data from the FOREST-HCM trial suggests use of aficamten could help patients with obstructive hypertrophic cardiomyopathy (oHCM) avoid needing to undergoing septal reduction therapy (SRT).

American Heart Association (AHA) Annual Scientific Sessions 2024

data from a subgroup analysis of the trial suggested 97% of SRT-eligible patients included in the trial were no longer eligible after 24 weeks of treatment with aficamten.

“This is an open level study, so you can't always take everything from it and say, ‘I have the highest level of evidence [and] that this is being achieved’. However, what I would argue is day in, day out, in the clinic, this is what we use to treat patients,” explained Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University, in an interview with HCPLive. “We use their symptoms, their LVOT gradient, how they feel, my impression or the physician's impression of what's going on, and we recommend to them surgery or no surgery.”

An ongoing trial, FOREST-HCM is an open-label extension study of patients from the phase 2 REDWOOD-HCM or SEQUOIA-HCM trials. In the AHA 2024 analysis, investigators presented data on the effects among a subgroup of patients considered eligible for SRT from the study. Among the 180 patients with oHCM with at least 24 weeks of follow-up, 31.6% (n=57) were considered eligible for SRT at baseline.

Upon analysis, investigators found just 3.5% (n=2) of this subgroup remained eligible for SRT after 24 weeks of treatment. Investigators highlighted 35.1% (n=20) had a left ventricular outflow obstruction (LVOT) gradient of 50 mmHg or greater but were NYHA Class I/II and 3.5% (n=2) had NYHA III/IV but LVOT gradient less than 50 mmHg.

Further analysis suggested 92.9% (n=52) of SRT-eligible patients, as well as 67.8% of the remaining cohort, improved at least 1 NYHA class during by week 24. Additionally, investigators called attention to results indicated greater improvements were observed among SRT-eligible patients relative to those in remaining cohort (21.7 [SD, 19.3] vs 13.5 [SD, 13.9]; 

For more on this study and how it informs clinicians on the effects of aficamten among patients with oHCM, check out our interview with Masri from the floor at AHA 2024.

HCPLive Masri Aficamten SRT AHA 2024

Relevant disclosures for Masri include Cytokinetics, Bristol Myers Squibb, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, BioMarin, and AstraZeneca.

Efficacy and Safety of Aficamten in Patients Guideline-Eligible for Septal Reduction Therapy in the FOREST-HCM Trial.

 Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.

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The FOREST-HCM trial data suggests that aficamten may help patients with obstructive hypertrophic cardiomyopathy (oHCM) avoid septal reduction therapy (SRT). Presented at the AHA 2024, the trial's subgroup analysis showed that nearly 70% of SRT-eligible patients were no longer eligible after 24 weeks of aficamten treatment. The trial, an open-label extension of the REDWOOD-HCM and SEQUOIA-HCM trials, demonstrated significant improvements in NYHA class and left ventricular outflow tract (LVOT) gradient among patients, indicating potential benefits of aficamten in managing oHCM.

Ahmad Masri, MD, MS, discusses data from the FOREST-HCM trial examining effects of aficamten in patients with oHCM eligible for septal reduction therapy at baseline. 

Open-Label Study Finds Aficamten Could Help Most oHCM Patients Avoid Surgery

New research is shedding light on the evolving risk profile and baseline characteristics among patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the US.

, results of the study provide evidence of a changing risk profile and outcomes, which investigators suggest is indicative of the effects disease-modifying treatments, such as tafamidis, acoramidis, and vutrisiran, and diagnostic advances have had on earlier diagnosis of patients with ATTR-CM.

To better understand temporal trends in baseline risks of patients enrolled in trials for ATTR-CM, investigators designed their systematic review to leverage data from a search of the Embase, MEDLINE, and CENTRAL databases as well as conference websites on November 23, 2023, for peer-reviewed articles and abstracts. For the purpose of analysis investigator included randomized and single-arm clinical trials examining treatments for ATTR-CM. The primary interest of investigators was comparing baseline characteristics and outcomes in patients treated with placebo across the studies.

The review returned evidence suggesting several baseline characteristics were comparable across studies, including sex, age, race/ethnicity, genotype, and troponin I levels. However, notable differences were observed for characteristics such as improved NYHA class, with fewer patients classified as NYHA Class III, as well as improvements in NT-proBNP and eGFR levels in more recent studies.

Additionally, assessments of outcomes in the placebo groups suggested all-cause mortality (ACM) rates at 12 months decreased from 9% in ATTR-ACT (2013–2015 enrollment) to 6.9% in ATTRibute-CM (2019–2020 enrollment) and 5.6% in APOLLO-B (2019–2021 enrollment). At 30 months, ACM rates fell from 42.9% in ATTR-ACT to 25.7% in ATTRibute-CM.

For more on this study and how it might influence trials in the future, check out our interview with principal investigator Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University, from the floor at AHA 2024.

Recent Advances Have Improved Prognosis in ATTR-CM Patients, with Ahmad Masri, MD, MS

Evolving Baseline Risk in Patients With Transthyretin Amyloid Cardiomyopathy: A Systematic Literature Review of Clinical Trials

. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.

Campbell P. FDA accepts NDA submission for Acoramidis in attr-cm. HCP Live. February 6, 2024. Accessed November 21, 2024. https://www.hcplive.com/view/fda-accepts-nda-submission-for-acoramidis-in-attr-cm.

Iapoce C. Alnylam submits sNDA for vutrisiran for treatment of attr-cm. HCP Live. October 11, 2024. Accessed November 21, 2024. https://www.hcplive.com/view/alnylam-submits-snda-for-vutrisiran-for-treatment-of-attr-cm.

Ahmad Masri, MD, MS, discusses a study from AHA 2024 detailing changing risk profiles and outcomes in trials among patients with ATTR-CM.

Ahmad Masri, MD, MS

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