Presentation: Patient requiring mavacamten for the treatment of hypertrophic cardiomyopathy

A 45-year-old woman with known hypertrophic cardiomyopathy (New York Heart Association Class II) has been considered eligible for mavacamten by her specialist cardiology team. Before commencing treatment, the team plan to arrange CYP2C19 genotyping to guide dosing.

All patients should have CYP2C19 genotyping before commencing mavacamten therapy in order to determine the appropriate starting dose. This is because patients with a CYP2C19-poor metaboliser phenotype (which can be predicated by two CYP2C19 loss-of-function alleles) may have increased mavacamten exposure, leading to increased risk of systolic dysfunction (a type A adverse drug reaction).

• CYP2C19 genotyping is not currently available via the National Genomic Test Directory.
• The test is currently available as a ‘non-directory’ test via the North West Genomic Laboratory Hub (NWGLH). This assay tests for the *2 and *3 loss-of-function alleles in CYP2C19.
• • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• The *2 and *3 loss-of-function alleles are known to explain about 99% of reduced enzyme function in Asian ancestry populations (in which they are extremely common) and about 85% of reduced enzyme function in White populations.
• Because testing may be offered for other CYP2C19 loss-of-function alleles in the future, it is good practice to document which alleles were tested for in the local electronic health records.
• The non-directory test is currently funded by Bristol Myers Squibb as part of a package deal between it and the prescribing trust.
• If you have questions about this deal or wish to find out whether your trust has something similar in place, please contact your local Bristol Myers Squibb representative. CYP2C19 genotyping can still be ordered outside of the package deal, but it will not be reimbursed via Bristol Myers Squibb and individual trusts will be invoiced separately.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• European Medicines Agency: Camzyos
• Medicines and Healthcare products Regulatory Agency: Product search

For patients

• North West NHS Genomic Medicine Service Alliance: CYP2C19 testing to guide mavacamten dosing