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 II to III; and
• who are eligible for treatment with mavacamten in line with NICE technology appraisal guidance (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 for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• For information about the genes that 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.
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion) form.
• Testing is performed via loop-mediated isothermal amplification (LAMP) testing, and a fresh sample of EDTA blood (typically in a purple-topped tube) is required.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• 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

• European Medicines Agency: Camzyos
• Medicines and Healthcare products Regulatory Agency: Mavacamten
• NHS England: National Genomic Test Directory
• NICE: Mavacamten for treating symptomatic obstructive hypertrophic cardiomyopathy (TA913)

For patients

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