PRO-GENE Mava
Research type
Research Study
Full title
Precision Pharmacogenetics and Genotype Class Based Prediction of Mavacamten Response in Obstructive Hypertrophic Cardiomyopathy
IRAS ID
368062
Contact name
William Newman
Contact email
Sponsor organisation
University of Manchester
Clinicaltrials.gov Identifier
NCT07408427, Clinicaltrials.gov
Duration of Study in the UK
3 years, 0 months, 29 days
Research summary
This research aims to study personalised response to treatment for Hypertrophic Cardiomyopathy (HCM), a common inherited heart condition where the heart muscle thickens and contracts too vigorously. A new medication called mavacamten works by targeting the faulty muscle machinery called sarcomeres.
Early laboratory and scientific studies suggest that this drug might work differently depending on which specific faulty gene is causing the patient's disease. Specifically, the drug appears to be highly effective for patients with faults in "thick filament" proteins (myosin-driven disease) but may provide incomplete benefit for those with faults in "thin filament" proteins (calcium-driven disease).
Furthermore, mavacamten is processed by the liver enzyme called CYP2C19. While common genetic variations in this enzyme are known to affect drug levels, rare variants are not routinely tested, potentially leading to unpredictable drug responses or side effects.
We propose an observational study of adult patients who have symptomatic obstructive HCM and are starting mavacamten therapy as part of their routine care. We will use genetic testing (including sequencing for rare CYP2C19 alleles) to classify patients based on their unique genetic profile. We will then track their progress longitudinally using routine clinical data which are already performed as part of the participant's standard of care, such as heart scans, symptom scores (NYHA class), and blood tests (nT-proBNP) to see if their genetic profile predicts how well they respond to the drug.
The goal is to gather crucial evidence to help doctors better match patients to the right treatment based on their unique disease mechanism, moving closer to precision medicine.
REC name
Wales REC 6
REC reference
26/WA/0107
Date of REC Opinion
20 Apr 2026
REC opinion
Favourable Opinion