The U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for bezuclastinib in the treatment of advanced systemic mastocytosis (SM), Cogent Biosciences announced Sept. 15. It is now the third indication for which the company is seeking approval of this investigational oral drug.
The acceptance moves bezuclastinib a step closer to potential approval for advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm.. The FDA is expected to decide on the advanced SM application by June 29, 2027.
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The FDA application is based on data from the APEX trial, a pivotal study of bezuclastinib in people with advanced SM.
In the trial, 65% of patients with advanced SM taking bezuclastinib had a measurable response to treatment, and 57% achieved a complete or partial response, based on international criteria used to evaluate mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. therapies. After 12 months of treatment, 79% of patients were alive without disease progression, and 87% were alive overall, though the trial has not yet run long enough to determine median survival times.
Learn more: “New data shows bezuclastinib reduces disease activity in advanced SM”
Bezuclastinib is already under FDA review for nonadvanced SMNonadvanced SM In these subtypes of SM, mast cells accumulate in the body but do not usually cause severe organ damage. Nonadvanced SM includes the subtypes indolent SM and smoldering SM. and gastrointestinal stromal tumors (GIST), with decisions expected near the end of this year.
The central mechanism behind these diseases is a mutation in the KIT gene, which codes for a protein that normally helps regulate cell growth. In SM, a mutation called KIT D816V alters this protein so that it stays switched on, driving mast cells to multiply uncontrollably. Bezuclastinib is a tyrosine kinase inhibitor that specifically targets the mutated KIT protein; it is designed to shut down that faulty growth signal at its source.
“Together with the NDAs currently under review for NonAdvSM and GIST patients, this milestone further reinforces the potential of bezuclastinib across multiple patient populations with KIT-driven diseases,” said Andrew Robbins, president and chief executive officer of Cogent.
