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

Ahmad Masri, MD, MS

Navigating Treatment in ATTR-CM's New Era, with Ahmad Masri, MD, MS

The approvals of acoramidis (Attruby) and vutrisiran (Amvuttra) represent a step forward into a new era of management for 

transthyretin-mediated amyloidosis cardiomyopathy (ATTR-CM)

. Awarded in November 2024 and March 2025, respectively, the agents represent the latest in a new wave of therapeutic advancement, which now gives cardiologists multiple options boasting unique mechanisms of action.

“Everybody used to be offered tafamidis as a first-line therapy for patients with transact income. Now this has changed since the approval of acoramidis and the recent approval of vutrisiran. This has changed—now, you're going to sit with the patient, you're going to think about the options,” said Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University, in an interview with HCPLive at 

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

Acoramidis is an orally-administered near-complete stabilizer of transthyretin (TTR). Upon approval in November, the agent became the first approved product with a label specifying near-complete stabilization of TTR. The agent was approved based on data from the ATTRibute-CM study, which concluded use of acoramidis was associated with a statistically significant reduction in the primary endpoint of all-cause mortality and cumulative frequency of cardiovascular-related hospitalizations at 30 months.

Vutrisiran is a subcutaneous siRNA therapeutic that inhibits the production of TTR protein and was initially approved by the FDA for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis. The label expansion to include or the treatment of the cardiomyopathy of wild-type or hereditary ATTR-CM in adults to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits was based on the HELIOS-B trial, which concluded use was associated with a statistically significant benefit on all 10 prespecified primary and secondary endpoints.

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

 (acoramidis), a Near Complete TTR Stabilizer (≥90%), approved by FDA to Reduce Cardiovascular Death and Cardiovascular-related Hospitalization in ATTR-CM Patients - BridgeBio. BridgeBio. Published November 23, 2024. Accessed April 1, 2025. 

https://bridgebio.com/news/attruby-acoramidis-a-near-complete-ttr-stabilizer-%E2%89%A590-approved-by-fda-to-reduce-cardiovascular-death-and-cardiovascular-related-hospitalization-in-attr-cm-patients/

Alnylam Pharmaceuticals. Alnylam Announces FDA Approval of AMVUTTRA® (vutrisiran), the First RNAi Therapeutic to Reduce Cardiovascular. Investor Relations | Alnylam Pharmaceuticals, Inc. Published March 20, 2025. Accessed April 1, 2025. 

https://investors.alnylam.com/press-release?id=28831

Videos

Ahmad Masri, MD, MS, discusses how new options change the historic approach to the treatment of newly diagnosed ATTR-CM.  

 suggests prolonged treatment with aficamten was associated with favorable cardiac remodeling in 

obstructive hypertrophic cardiomyopathy (HCM)

, including reductions in left ventricular (LV) mass, left atrial (LA) volume, and mitral regurgitation (MR), while maintaining myocardial integrity.

“These are important results. The reason is not the fact that we only change the structure itself, the reason is that every single one of these structural changes, or every single one of these structural abnormalities at baseline has been associated or is associated with adverse outcomes on long-term follow-up,” explained lead investigator Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University, in an interview with HCPLive. “As such, the ability for a medication like aficamten to reverse remodel the ventricle in a favorable way, as well as the atrium, gives us clues that, longer term, we should expect to see improvement in patient outcomes, as well as improvement on how patients do in long term that the studies themselves might not be designed to measure.”

Under FDA review for an indication in obstructive HCM, with a decision expected in September 2025, aficamten is a next-generation cardiac myosin inhibitor developed by Cytokinetics. The ACC.25 presentation by Masri examined data from FOREST-HCM, an open-label extension study of patients from the phase 2 REDWOOD-HCM trial and phase 3 SEQUOIA-HCM trial, the latter of which was used in support for the aforementioned application to the FDA.

As part of FOREST-HCM, a 5-year cardiac magnetic resonance (CMR) imaging sub-study was conducted to assess structural and functional changes in patients receiving aficamten.

Between May 2021 and August 2024, 292 patients with obstructive HCM were enrolled in FOREST-HCM, with 89 (30%) participating in the CMR sub-study. Of these, 31 patients (mean age 62 ±13 years, 58% female) completed both baseline and follow-up CMR. Investigators pointed out 9 patients had their baseline CMR from the SEQUOIA-HCM trial and 72 weeks of follow-up, while 22 had baseline imaging at the start of FOREST-HCM and 48 weeks of follow-up.

After 48 to 72 weeks, use of aficamten was associated with significant reductions were observed in LV mass index (-10 [SD, 18] g/m²), maximal LV wall thickness (-2 [SD, 2] mm), LA volume (-19 [SD, 24] mL), MR volume (-17 [SD, 21] mL), and MR fraction (-11% [SD, 17]),(

<.0001). Investigators pointed out myocardial fibrosis remained stable, as evidenced by unchanged LV late gadolinium enhancement mass (-0.4 [SD, 4] g, 

= .48) and global extracellular volume (-0.7% [SD, 2.5]; 

= .08). Investigators also called attention to small but statistically significant decrease in LVEF (-4% [SD, 6], 

= .0002) was observed from a baseline of 68% (SD, 5%).

For more on these results, check out our interview with Masri from ACC.25.

Ahmad Masri, MD, MS, on FOREST-HCM CMR Substudy

Masri A, Cardoso R, Nassif M, et al. EFFECT OF AFICAMTEN TREATMENT FOR UP TO 72 WEEKS ON CARDIAC STRUCTURE AND FUNCTION IN PATIENTS WITH OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY: THE SEQUOIA-HCM AND FOREST-HCM CMR SUB-STUDIES. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

Cytokinetics. Cytokinetics Announces FDA Acceptance of New Drug Application for Aficamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy | Cytokinetics, Inc. Cytokinetics, Inc. Published December 2, 2024. Accessed April 1, 2025. 

https://ir.cytokinetics.com/news-releases/news-release-details/cytokinetics-announces-fda-acceptance-new-drug-application-0

Ahmad Masri, MD, MS, discusses data detailing the effects of aficamten in oHCM from the FOREST-HCM OLE study at ACC.25.

Aficamten and Cardiac Remodeling in FOREST-HCM, with 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

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.

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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