Section 3 of 6
Product information and disease description
64 evidence topics · 44 sources
Product description
Phase of product development
Orphan designation and approval status
Regulatory submission: NDA submitted December 2025
Breakthrough Therapy Designation: designated populations
Launch: Anticipated in the second half of 2026
Product information
Generic, brand name and therapeutic class of product
Brand name
No evidence found.
Dosage forms and strengths
Marketed dosage strengths
Not applicable.
Cogent clinical drug-product safety data sheet
No evidence found.
Average sales price and wholesale acquisition cost
Not applicable.
American hospital formulary service (AHFS), or other drug classification
Mechanism-based drug classification
Indication
Population under investigation
Pharmacology
Mechanism of action
Pharmacodynamics
Nonclinical central nervous system exposure
Pharmacokinetics
Pharmacokinetics: healthy-adult, single-dose formulation study
Elimination half-life: healthy-adult, single-dose formulation study
Contraindications/Warnings/Precautions/Adverse effects
Warnings and precautions
Not applicable.
Special populations
No evidence found.
Drug/Drug, drug/disease interactions
Effects of other drugs on Bezuclastinib
SUMMIT protocol exclusion: recent strong CYP3A4 inhibition or induction
Effects of Bezuclastinib on other drugs
No evidence found.
Dosing and administration
Dosage
Bezuclastinib dose in SUMMIT Part 2
Administration
SUMMIT protocol: oral administration and treatment cycles
Access and distribution
Co-prescribed/Concomitant therapies
SUMMIT background therapy
SUMMIT protocol: maximum concomitant prednisone dose
Effect of Bezuclastinib on quality measures
Bezuclastinib-specific quality-measure findings
No evidence found.
Product comparison
Comparator assessment of avapritinib by IQWiG: assessed population
Comparator assessment of avapritinib by IQWiG: assessment result
Place of product in therapy
Disease description
Definition and etiology
Nonadvanced systemic mastocytosis subtypes
Epidemiology
Incidence of Nonadvanced systemic mastocytosis
Denmark: mean annual ISM incidence, 1997–2021
| Population and unit | Incidence and 95% confidence interval |
|---|---|
| ISM, per 100,000 person-years | “0.43 (0.32–0.55)” |
Prevalence of Nonadvanced systemic mastocytosis
Epidemiology in Denmark: study classification
Epidemiology in Denmark: ISM prevalence as of January 1, 2022
Natural history, survival, and mortality
Denmark: 10-year survival probability in the ISM group
Pathophysiology
Diagnosis
Updated diagnostic criteria and classification of mast cell disorders
Consensus diagnostic rule: major and minor criteria
Clinical presentation - signs and symptoms
Dermatological symptoms: MS2D2 domains
Gastrointestinal and pain symptoms: MS2D2 domains
Neurocognitive symptoms: MS2D2 domains
Fatigue symptoms: MS2D2 domains
Long-term morbidity
Skeletal morbidity and fracture potential
Burden of Nonadvanced systemic mastocytosis
Humanistic burden and health-related quality of life
Humanistic and productivity burden: U.S. systemic mastocytosis survey
Economic burden and healthcare resource utilization
U.S. healthcare costs: nonadvanced SM versus matched non-SM controls
Healthcare resource utilization and medication burden
SUMMIT: changes in best supportive care medication use
Economic impact of Nonadvanced systemic mastocytosis on families
Patient and caregiver employment burden
Economic impact of diagnostic testing
No evidence found.
Approaches to treatment
Current treatment options and standard of care
Trigger avoidance and patient education
Avoidance of individual mast-cell activation triggers
H1 and h2 antihistamines
Histamine-receptor blockade
Second-generation H1 antihistamines
Proton pump inhibitors
Additional acid suppression
Leukotriene receptor antagonists
Leukotriene-pathway inhibition
Mast cell stabilizers
Mast-cell stabilization
Epinephrine
Emergency preparedness: prior severe anaphylaxis or insect venom allergy
Corticosteroids
Severe refractory symptoms: short-term glucocorticoids
Anti-IgE monoclonal antibodies
Recurrent uncontrolled anaphylaxis: anti-IgE therapy
KIT tyrosine kinase inhibitors
Existing FDA-approved targeted treatment: avapritinib
Cytoreductive therapies
Bone-directed therapies
Bisphosphonates for skeletal disease
Venom immunotherapy
Severe anaphylaxis following Hymenoptera stings
Vascular laser therapy
Telangiectatic or pigmentary skin lesions
Clinical trials
French guidelines for nonadvanced mastocytosis in adults
Limitations of current therapies
Summary
Current care includes trigger avoidance, symptom-directed medicines, anaphylaxis preparedness, and treatment of skeletal complications. Avapritinib is FDA approved for adults with ISM. SUMMIT nevertheless enrolled participants with inadequate symptom control despite at least two anti-mediator therapies. The available evidence therefore describes a population with persistent symptoms on existing care; it does not establish that all treated people with nonadvanced SM require a KIT inhibitor. The effect of KIT inhibition on disease progression is not established.
Review focused on indolent systemic mastocytosis
Place in treatment, anticipated use, and care setting
Summary
The documented use of bezuclastinib is investigational. SUMMIT Part 2 evaluated 100 mg daily with best supportive care in nonadvanced SM with inadequate symptom control despite at least two anti-mediator therapies. Expanded-access protocols are described for eligible people with SM, subject to protocol-specific criteria. These trial and expanded-access arrangements do not constitute an approved routine-care indication.
Heterogeneity of treatment effect
Treatment-by-subgroup interaction testing
No evidence found.
Care management intervention strategies
Standardized screening and diagnostic testing
Other product development or post-marketing obligations required by the FDA
Not applicable.
Ongoing post-approval monitoring
Not applicable.