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).

Testing is available through the National Genomic Test Directory for patients with:

• symptomatic obstructive hypertrophic cardiomyopathy who have a New York Heart Association class of 2 to 3; and
• who are eligible for treatment with mavacamten in line with NICE TA 913 (where mavacamten is an add on to individually optimised standard care that includes beta blockers, non-dihydropyridine calcium channel blockers or disopyramide, unless these are contraindicated).

• Consult the National Genomic Test Directory. From here, you can access the rare and inherited disease eligibility criteria document, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet that contains details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• For this indication, the appropriate panel to choose is:
  • R454 Mavacamten for treating symptomatic obstructive hypertrophic cardiomyopathy: This is a targeted test for the *2 and *3 loss of function and *17 increased function alleles in CYP2C19.
• 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.
• Testing is performed via loop-mediated isothermal amplification (LAMP) testing, and therefore a fresh sample of EDTA blood (typically a purple-topped tube) is required.
• To find out the procedure for completing test order forms and obtaining patient consent for testing, contact your local Genomic Laboratory Hub.
• Information about patient eligibility and test indications were 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

• National Genomic Test Directory
• NICE: Mavacamten for treating symptomatic obstructive hypertrophic cardiomyopathy (TA913)
• 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