AYVAKYT (avapritinib) - Indolent systemic mastocytosis (ISM)

The Committee deems that the clinical benefit of AYVAKYT 25 mg (avapritinib) film-coated tablets is moderate in the MA indication.

Considering:

• demonstration of the superiority of AYVAKYT (avapritinib) compared to placebo, administered in combination with the best supportive care on:
  • the mean change from baseline to week 24 in ISM-SAF TSS, the primary endpoint (the
    absolute difference = -6.43 points, CI95%= [-10.90, -1.96], p =0.003),
  • the five ranked secondary endpoints, in particular the percentage of patients achieving a ≥ 50% reduction in ISM-SAF TSS (24.8% in the avapritinib 25 mg group versus 9.9% in the placebo group, OR = 3.10, CI95%= [1.24; 8,64]), p=0.005),

and despite:

• the limited clinical relevance of the difference observed between the avapritinib group and the placebo group, in terms of mean change from baseline to week 24 in ISM-SAF TSS, the primary endpoint (-6 points in ISM-SAF TSS measured on a 110-point scale),
• the lack of any established correlation between the secondary endpoints concerning biomarkers and the clinical response (serum tryptase level, reduction in KIT D816V mutant allele fraction and reduction in bone marrow mast cell infiltrate),
• the absence of comparison during the additional follow-up period of almost one year (part 3 of the study),
• the exploratory nature of the quality of life data,
• the safety profile, mainly marked by the occurrence of anaphylactic reactions, which are also frequent manifestations of indolent systemic mastocytosis.
• the limited safety data in terms of the follow-up duration, with a median follow-up of less than 2 years.

the Committee deems that AYVAKYT (avapritinib) 25 mg film-coated tablets provides a minor clinical added value (CAV IV) in the current care pathway, which includes the relevant comparators.