Will the FDA approve bezuclastinib for the treatment of patients with nonadvanced systemic mastocytosis?
The FDA has accepted a new drug application (NDA) seeking the approval of bezuclastinib (CTG9486) for the treatment of patients with nonadvanced systemic mastocytosis.1
The regulatory agency has assigned a target action date of December 30, 2026, under the Prescription Drug User Fee Act.
The NDA is supported by
Findings presented at the
Additionally, 95.4% of patients in the bezuclastinib arm achieved at least a 50% reduction in serum tryptase levels compared with 0% in the placebo arm (P < .0001). At least a 50% reduction or clearance of mast cell aggregates occurred in 88.2% of patients in the bezuclastinib group vs 25.5% of patients in the placebo group (P < .0001). KIT p.D816V variant allele frequency (VAF) was reduced by at least 50% in 97.5% of patients administered bezuclastinib vs 0% of patients given placebo (P < .0001).
SUMMIT was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled patients with indolent systemic mastocytosis, smoldering systemic mastocytosis, or bone marrow mastocytosis who had inadequate symptom control despite receiving at least 2 anti-mediator therapies.
In the first part of the study, investigators conducted a 12-week, double-blind treatment period in order to establish the selected dose of bezuclastinib for part 2. In part 2, patients were randomly assigned 2:1 to receive bezuclastinib at 100 mg once per day in combination with best supportive care (BSC), or placebo plus BSC, for 24 weeks. Following the 12-week treatment period in part 1 and the 24-week treatment period in part 2, patients were allowed to proceed to an open-label extension period, which further evaluated the safety and tolerability of bezuclastinib.
The primary end point in part 2 was the mean change in TSS from baseline to week 24 per the mastocytosis symptom severity daily diary (MS2D2). Secondary end points comprised the proportion of patients to achieve at least a 50% reduction in serum tryptase levels, KIT p.D816V VAF, bone marrow mast cell burden, and MS2D2 TSS, as well as those who had at least a 30% reduction in MS2D2 TSS.
Any-grade treatment-emergent adverse effects (TEAEs) occurred in 98.3% of patients in the bezuclastinib arm (n = 118) compared with 88.3% of patients in the placebo arm (n = 60). The rates of serious TEAEs were 4.2% and 5%, respectively. Drug-related TEAEs led to treatment discontinuation in 11% of patients in the experimental group vs 5.9% of patients in the control arm. All treatment-related discontinuations were related to elevated transaminase levels, and these toxicities all resolved following discontinuation.
The most common any-grade TEAEs reported in at least 10% of patients in the bezuclastinib arm included hair color changes (bezuclastinib, 69.5%; placebo, 5.0%), altered tasted (23.7%; 0%), nausea (22.0%; 13.3%), increased alanine aminotransferase or aspartate aminotransferase levels (22.0%; 6.6%), headache (17.8%; 11.7%), alopecia (11.9%; 3.3%), and increased alkaline phosphatase levels (10.2%; 3.3%).
