.SunPharma's oral small-molecule drug Leqselvi (deuruxolitinib) is now available in the US for the treatment of adults with severe alopecia areata.
Alopecia areata is an autoimmune disease in which the immune system attacks hair follicles, causing partial or complete hair loss on the scalp and body. The scalp is the most common site of involvement, but any hairy area can be affected, alone or in conjunction with the scalp. The disease can be lifelong and can affect both men and women. Alopecia areata can be associated with serious psychological consequences, including anxiety and depression. Currently, there are limited approved treatments for alopecia areata.
Leqselvi is a twice-daily oral selective Janus kinase (JAK) inhibitor, specifically targeting JAK1 and JAK2, designed to block JAK1 and JAK2. These two enzymes are believed to play a key role in the pathogenesis of severe alopecia areata. By disrupting these pathways, Leqselvi aims to halt the progression of hair loss and promote hair regrowth.
The approval of this drug for the treatment of severe alopecia areata (at least 50% hair loss on the scalp) in adults is based on positive results from two phase 3 clinical trials: THRIVE-AA1 (ClinicalTrials.gov identifier: NCT04518995) and THRIVE-AA2 (ClinicalTrials.gov identifier: NCT04797650). The results showed that a higher proportion of patients treated with Leqselvi achieved scalp hair coverage of 80% or more compared to patients receiving placebo.
Leqselvi is available in tablet form containing 8 mg of deuruxolitinib. The recommended dose is 8 mg twice daily. Treatment may need to be interrupted if a serious infection or hematological abnormality occurs.
Some evaluations and immunizations are recommended before starting Leqselvi treatment. These assessments and immunizations include: CYP2C9 genotyping (contraindicated in patients with poor CYP2C9 metabolizers); evaluation of combination therapy with CYP2C9 inhibitors (contraindicated with intermediate- to high-potency CYP2C9 inhibitors); assessment of active and latent tuberculosis (TB) (not recommended for patients with active TB); screening for viral hepatitis (not recommended for patients with active hepatitis B or C); screening for hepatitis B infection; complete blood count (not recommended if absolute lymphocyte count <500/mm³, absolute neutrophil count <1000/mm³, or hemoglobin <8 g/dL); and completion of necessary immunizations (including herpes zoster).
The most common adverse reactions to Leqselvi include headache, acne, nasopharyngitis, elevated serum creatine phosphokinase, hyperlipidemia, fatigue, weight gain, lymphopenia, thrombocytosis, anemia, skin and soft tissue infections, neutropenia, and herpes.
Like other JAK inhibitors, Leqselvi's prescribing information includes a boxed warning about the risks of serious infections, all-cause mortality, malignancy, major adverse cardiovascular events, and thrombosis. Other warnings and precautions include an increased risk of gastrointestinal perforation and elevated blood lipids.
