The U.S. Food and Drug Administration (FDA) has approved Leqselvi (deuruxolitinib) 8 mg tablets, a novel oral Janus kinase (JAK) inhibitor, for the treatment of adults with severe alopecia areata. This approval marks a significant advancement in the treatment landscape for this autoimmune condition, which affects approximately 700,000 people in the United States, with 300,000 experiencing severe forms.
Mechanism of Action
Leqselvi functions as a selective inhibitor of JAK1 and JAK2, key enzymes involved in immune signaling pathways. In alopecia areata, the immune system attacks hair follicles, leading to hair loss. By inhibiting JAK1 and JAK2, deuruxolitinib interrupts these pathways, reducing the immune response and promoting hair regrowth.
Clinical Trial Data
The FDA's decision was supported by data from two Phase 3 clinical trials, THRIVE-AA1 and THRIVE-AA2, which enrolled 1,220 patients with at least 50% scalp hair loss for over six months. At baseline, patients had an average of only 13% scalp hair coverage. After 24 weeks, more than 30% of patients taking Leqselvi achieved 80% or more scalp hair coverage (SALT ≤20). Up to 25% of patients regained almost all of their scalp hair (≥90% coverage).
Efficacy and Safety Profile
The trials demonstrated a consistent upward trend in the number of patients achieving a SALT score of ≤20 throughout the 24-week period. Discontinuation rates due to adverse reactions were low (3.1%). Common adverse events included headache (12.4% vs. 9.4% with placebo), acne (10% vs. 4.3% with placebo), and nasopharyngitis (8.1% vs. 6.7% with placebo).
Safety Considerations
Leqselvi carries warnings regarding serious infections, malignancies, thrombosis, and gastrointestinal perforations. It is contraindicated in CYP2C9 poor metabolizers and those taking moderate or strong CYP2C9 inhibitors. Monitoring for lipid elevations, anemia, neutropenia, and lymphopenia is recommended. The drug also carries a boxed warning for increased risk of mortality and major cardiovascular events, similar to other JAK inhibitors used in rheumatoid arthritis.
Dosing and Administration
The recommended dosage of Leqselvi is 8 mg orally twice daily, with or without food. Prior to treatment, evaluations should include CYP2C9 genotype, tuberculosis screening, viral hepatitis screening, and a complete blood count.
Impact on Alopecia Areata Community
The approval of Leqselvi represents a significant advancement for individuals with severe alopecia areata, offering a new oral treatment option with proven efficacy. Sun Pharma is committed to supporting the alopecia areata community through an access program to help eligible patients initiate and continue treatment.
