Bezuclastinib

In the Danish register study, all nonadvanced SM was classified as ISM; prevalence on January 1, 2022 was 9.36 per 100,000. In a U.S. survey of people with SM, 54% reduced work hours and 64% avoided leaving home because of symptoms. These survey estimates are not specific to nonadvanced disease. A separate matched-control study reported mean post-index medical costs of $24,588 for nonadvanced SM versus $14,419 for controls.

SUMMIT Part 2 randomized 179 participants, 119 to bezuclastinib and 60 to placebo. Reported mean TSS reductions at week 24 were 24.3 and 15.4 points, respectively (p=0.0002). At least 50% TSS reduction occurred in 34.3% versus 18.1%. In the intention-to-treat biomarker analysis, at least 50% serum tryptase reduction occurred in 104/119 participants (87.4%) versus 0/60. Hair color change occurred in 69.5% versus 5.0%; ALT/AST elevations occurred in 22.0% versus 6.6%. Treatment-related discontinuations occurred in 5.9% of bezuclastinib recipients, all due to transaminase elevations that subsequently resolved.

Bezuclastinib remains investigational in the regulatory evidence reproduced here. The FDA review announcement gives a December 30, 2026 target action date. SUMMIT provides placebo-controlled evidence of symptom and biomarker improvement, with transaminase elevations contributing to treatment discontinuation. The effect of KIT inhibition on disease progression remains uncertain. Comparator avapritinib evidence does not establish a direct comparison with bezuclastinib.