Avapritinib (Ayvakyt)

Key Messages

• Canada’s Drug Agency (CDA-AMC) recommends that Ayvakyt be reimbursed by public drug plans for adult patients with indolent systemic mastocytosis (ISM) with moderate to severe symptoms inadequately controlled on symptomatic treatment, if certain conditions are met.
• The pan-Canadian Oncology Drug Review Expert Review Committee (pERC) determined that it is uncertain whether Ayvakyt demonstrates acceptable clinical value versus symptomatic treatments in adult patients with ISM who have moderate to severe symptoms inadequately controlled on symptomatic treatment. Therefore, the committee also considered whether Ayvakyt addresses a significant unmet clinical need.
• Evidence from 1 clinical trial showed that Ayvakyt in combination with symptomatic treatment may result in added clinical benefit, compared with placebo in combination with symptomatic treatment, as per the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) total symptom score (TSS). However, the evidence for Ayvakyt is uncertain because there were differences between groups in terms of prognostic factors as well as in the occurrence of edema, which might have allowed patients to infer treatment allocation. The effect of Ayvakyt to reduce anaphylaxis was also uncertain due to the small number of events.
• ISM is a rare disease that can cause life-threatening anaphylaxis. Current treatment options available to patients with ISM in Canada only palliate the symptoms. pERC determined that Ayvakyt may meet some of the unmet clinical need in terms of improving disease symptoms with an acceptable safety profile.
• Based on all of the preceding considerations, pERC recommended that Ayvakyt be reimbursed.
• Ayvakyt should only be covered when used in conjunction with symptomatic treatments in adult patients with a confirmed diagnosis of ISM with a KIT D816V mutation, and who have moderate to severe disease based on the clinician’s assessment, with no clinical improvement in at least 1 type of symptom after receiving at least 2 prior symptomatic treatments, as determined by the clinician.
• Ayvakyt should only be reimbursed if the treatment is initiated by a hematologist, allergist, or immunologist with expertise in the diagnosis, treatment, and response evaluation of patients with ISM, and if the cost of Ayvakyt is reduced. Reimbursement of Ayvakyt may be continued for patients with disease response to treatment, as assessed by the treating clinician every 24 weeks. Reimbursement of Ayvakyt should be discontinued in cases of unacceptable toxicity, failure to meet follow-up requirements, or lack of clinical benefit as determined by the treating clinician.