Fady I. Malik works in Heart Failure / Cardiomyopathy affiliated with Cytokinetics (United States).
Fady I. Malik, M.D., Ph.D., is Executive Vice President of Research and Development at Cytokinetics and a Clinical Professor of Medicine in the Cardiology Division at the University of California, San Francisco. He joined Cytokinetics at its founding in 1998 and previously practiced as an attending interventional cardiologist at the San Francisco VA Medical Center and UCSF Medical Centers until 2019. His research has focused on cardiac myosin modulators, including omecamtiv mecarbil for systolic heart failure and aficamten for hypertrophic cardiomyopathy.
221 pubs · 6,764 cites · h-index 40
MD
University of California, San Francisco
1994
PhD
University of California, San Francisco
BS, Bioengineering
University of California, Berkeley
Executive Vice President, Research and Development
Cytokinetics · 2015 - Present
Clinical Professor of Medicine, Cardiology Division
University of California, San Francisco · 2000 - Present
Director
Rocket Pharmaceuticals · 2022 - Present
Attending Interventional Cardiologist
San Francisco VA Medical Center · 2001 - 2019
Senior Vice President, Research and Development
Cytokinetics · 2014 - 2015
JACC Heart FailureRuppert et al.RCT
In patients with HFrEF, omecamtiv mecarbil appears less effective in those with prolonged QRS duration who do not have a CRT device, but remains beneficial in CRT-treated patients regardless of QRS duration.
Journal of Cardiac FailureMassera et al.Original Research
Supports LVEF monitoring with long-term aficamten in obstructive HCM; leaves open reversibility and clinical impact of systolic dysfunction.
ACS Medicinal Chemistry LettersAshcraft et al.preclinical
Supports Phase II evaluation in HFpEF; leaves open differentiation from other myosin inhibitors via distinct binding site.
Heart Failure / Cardiomyopathy · Brigham and Women's Hospital
Based on this trial, this is the first-ever successful therapy for nonobstructive hypertrophic cardiomyopathy. These results are highly encouraging for patients with this condition and for cardiologists who struggle to help them.
CirculationHegde et al.RCT
An exploratory analysis of ACACIA-HCM evaluated echocardiograms from 517 patients with symptomatic nonobstructive hypertrophic cardiomyopathy receiving aficamten or a placebo. From a mean baseline of 68%, the drug decreased left ventricular ejection fraction by 4.6% compared with placebo at 36 weeks. However, it improved multiple measures of diastolic function. The authors conclude the drug's benefits extend beyond reducing outflow tract gradients.
Heart Failure / Cardiomyopathy · Lahey Medical Center
More than half of aficamten-treated patients achieved improvement across three or more of the five clinical, functional and biological measures evaluated, compared with 13% of placebo-treated patients.
New England Journal of MedicineMasri et al.
Heart Failure / Cardiomyopathy · Brigham and Women's Hospital
What happens if you put all of these together and define a clinical response as a positive result on three or more of these outcomes? That happened in 53% of those randomized to aficamten vs 13% of those on placebo, which was highly significant [P =.001]
CirculationMaron et al.RCT
The ACACIA-HCM trial tested daily aficamten against a placebo in patients with symptomatic nonobstructive hypertrophic cardiomyopathy. At 36 weeks, 53% of patients on aficamten achieved a partial or complete response, meaning they improved on at least three of five measures of symptoms, exercise, left atrial volume, diastolic function, or NT-proBNP, versus 14% on the placebo. The gain in exercise capacity alone was not significant. Aficamten shows potential benefit for a condition with no approved treatments.
Journal of Cardiac FailureMasri et al.meta-analysis
Pooled data from SEQUOIA-HCM and MAPLE-HCM analyzed over 440 patients with symptomatic obstructive hypertrophic cardiomyopathy taking aficamten, metoprolol, or a placebo. The study found that a 0.35 mL/kg/min increase in peak oxygen uptake represents a perceptible clinical improvement. At 24 weeks, 60% of patients on aficamten reached this threshold, versus 31% on placebo or metoprolol. Clinicians can use this benchmark to interpret exercise testing.
Heart Failure / Cardiomyopathy · Brigham and Women's Hospital
Currently, there are no evidence-based therapies that are available to help us treat these patients. While we use beta blockers and calcium channel blockers in certain patients, there are no proven therapies that can help these patients feel better or improve the function of the heart.
Journal of the American College of CardiologyMasri et al.
JACCO’Connor et al.review
A multi-stakeholder consensus identified key challenges in heart failure clinical trials and recommended strategies to improve efficiency, including the creation of a Heart Failure Collaboratory.
Heart Failure / Cardiomyopathy · Brigham and Women's Hospital
These additional analyses from MAPLE-HCM expand on the primary finding that aficamten is superior to metoprolol on exercise capacity, with new insights into the overall treatment effect of aficamten as well as its effect on symptoms and biomarkers in comparison to metoprolol. What's notable is patients treated with aficamten achieved a significantly greater number of clinical response categories compared with metoprolol, and that nearly 40% achieved significant improvements in patient reported symptoms.
Journal of the American College of CardiologyNassif et al.
Cardiomyopathy and Myosin Studies · Lahey Hospital and Medical Center
Treatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures. These results underscore the wide-ranging potential of aficamten for treatment of patients with symptomatic oHCM.
Journal of the American College of CardiologyWang et al.
JACCLakdawala et al.Original Research
Cardiomyopathy and Myosin Studies · University of Michigan
What we are seeing is actually a rapid, pretty robust and sustained reduction in outflow obstruction with maintenance of LV systolic function over that time period, along with significant improvements in how patients report to us that they feel in terms of assessments by KCCQ.
European Heart JournalTower‐Rader et al.
European Journal of Heart FailureFoà et al.RCT
May reduce arrhythmic events in LVEF ≤28% HFrEF; extends OM evidence to sudden death prevention.
Muscle & NerveRudnicki et al.RCT
Trial evaluates the impact of durable medical equipment use on clinical outcomes in ALS patients, indicating its importance in trials.
European Journal of Heart FailureChimura et al.RCT
Moderate mitral regurgitation is present in approximately 15% of HFrEF patients and independently predicts a higher risk of heart failure events or cardiovascular death, without modifying the treatment effect of omecamtiv mecarbil.
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam)Ono et al.cohort
Elevated baseline LDH levels are independently associated with a higher risk of cardiovascular death or heart failure events in patients with HFrEF, providing incremental prognostic value.
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam)Ono et al.cohort
Higher dipstick proteinuria levels are independently associated with an increased risk of adverse clinical outcomes in patients with HFrEF, particularly those with preserved eGFR.
Circulation Heart FailureKantor et al.Blinded Clinical Trial
The CEDAR-HCM trial is designed to evaluate the efficacy and safety of the cardiac myosin inhibitor aficamten in children and adolescents with symptomatic obstructive hypertrophic cardiomyopathy.
