New data from the SUMMIT trial has highlighted encouraging progress for patients living with non-advanced systemic mastocytosis (NonAdvSM). This rare and chronic disorder arises when mast cells accumulate in tissues, leading to unpredictable and sometimes debilitating symptoms that affect the skin, gastrointestinal system, and other organs. For many, the condition can significantly impair daily life, and treatment options have remained limited.

Cogent Biosciences announced that its investigational drug, bezuclastinib, successfully met both primary and secondary endpoints in Part 2 of the SUMMIT study. The findings demonstrate not only symptom relief but also a measurable impact on markers of mast cell activity.

Symptom Improvement and Clinical Outcomes

The primary goal of the trial was reduction of total symptom score after 24 weeks. Patients who received bezuclastinib achieved a mean reduction of 24.3 points, compared with 15.4 points in the placebo arm. This translated into a placebo-adjusted improvement of 8.91 points, which was statistically significant and clinically meaningful.

For patients who experience persistent fatigue, skin lesions, abdominal pain, and an array of allergic-type symptoms, even modest improvements can represent an important shift in quality of life. The magnitude of symptom reduction seen in SUMMIT suggests that bezuclastinib could deliver meaningful relief beyond what is typically expected from supportive therapies alone.

In addition to symptoms, the trial tracked disease-related biomarkers. A striking 87.4% of patients treated with bezuclastinib achieved at least a 50% reduction in serum tryptase levels, compared with none in the placebo group. Since tryptase is directly linked to mast cell burden, this result points to a biological impact of therapy that goes deeper than symptom management.

Safety Profile and Next Steps

Safety data presented alongside efficacy findings were favourable. Bezuclastinib was generally well tolerated, with side effects that were manageable and consistent with expectations. No major unexpected safety issues were identified, supporting the potential for long-term use in a chronic disease setting.

Building on these results, Cogent plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration before the end of 2025. The company is also expanding its development program to evaluate the drug in advanced systemic mastocytosis as well as other mast cell-driven conditions such as gastrointestinal stromal tumours.

For patients and clinicians, the SUMMIT trial findings mark a meaningful advance. While systemic mastocytosis remains a complex condition with varied presentation, the possibility of a therapy that both relieves symptoms and reduces disease activity is a welcome step forward. Bezuclastinib could soon provide a new standard of care for individuals who have had limited options until now.

Cogent is now preparing to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration by the end of 2025 for bezuclastinib in NonAdvSM. In addition, further pivotal trials are underway or planned, including studies in advanced systemic mastocytosis and gastrointestinal stromal tumours.

For patients with NonAdvSM this could be a major development. Many current treatments focus on managing symptoms, but do not sufficiently reduce mast cell burden or alter disease biology. If approved, bezuclastinib may become a valuable option that addresses both the symptomatic and the underlying components of the disease.