Leqselvi from Sun Pharmaceutical Industries

The FDA has approved deuruxolitinib oral tablets (Leqselvi; Sun Pharmaceutical Industries Ltd) to treat adults with severe alopecia areata, although commercial launch is indefinitely delayed due to a patent dispute.^1,2 The approval carries the limitation that deuruxolitinib should not be used in combination with biologic immunomodulators, cyclosporine, Janus kinase (JAK) inhibitors, or potent immunosuppressants.¹ Alopecia areata is an autoimmune disease that occurs when the immune system targets hair follicles, resulting in hair loss on the body, face, and scalp. Approximately 700,000 individuals in the US are affected by the condition, which can be associated with anxiety and depression.³

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PHARMACOLOGY AND PHARMACOKINETICS

Deuruxolitinib is a JAK inhibitor. JAK inhibitors mediate the signaling of cytokines and growth factors that contribute to hematopoiesis and immune function. Deuruxolitinib reaches peak plasma concentrations within 1.5 hours of oral administration and steady-state plasma concentrations within 1 to 2 days. Its mean elimination half-life is approximately 4 hours.¹

DOSING AND ADMINISTRATION

The recommended dose of deuruxolitinib is 8 mg orally twice per day. Before beginning treatment, patients should be tested for CYP2C9 variants to determine CYP2C9 genotype, and the concomitant use of CYP2C9 inhibitors should be evaluated. Patients should also be screened for tuberculosis and viral hepatitis, have a complete blood count obtained, and complete any necessary immunizations prior to initiating deuruxolitinib.¹

CLINICAL TRIALS

Deuruxolitinib was evaluated in 2 double-blind, multicenter, placebo-controlled, randomized phase 3 clinical trials, THRIVE-AA1 (NCT04518995) and THRIVE-AA2 (NCT04797650). The trial included adults with alopecia areata who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT) for more than 6 months. Participants were randomly assigned to receive deuruxolitinib 8 mg twice daily, deuruxolitinib 12 mg twice daily, or placebo twice daily for 24 weeks.

Both trials met the primary end point, which was the proportion of participants who achieved at least 80% scalp hair coverage (SALT score of ≤20) at week 24. For participants using deuruxolitinib 8 mg twice daily in THRIVE-AA1, 29% achieved a SALT score of 20 or less compared with 1% of patients using placebo, and 20% using deuruxolitinib achieved a SALT score of 10 or less compared with 0% using placebo. For participants receiving deuruxolitinib 8-mg twice daily in THRIVE-AA2, 32% achieved a SALT score of 20 or less compared with 1% using placebo, and 24% using deuruxolitinib achieved a SALT score of 10 or less compared with 0% using placebo.

Secondary outcomes included the percentage of participants who responded “satisfied” or “very satisfied” at week 24 on the Satisfaction of Hair Patient-Reported Outcome. This consisted of 42% of the deuruxolitinib 8 mg participants compared with 5% of the placebo group in THRIVE-AA1, and 46% of the deuruxolitinib 8-mg participants compared with 2% of the placebo group for THRIVE-AA2.^1,3

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Deuruxolitinib carries a boxed warning regarding the risk of infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis during treatment. The use of deuruxolitinib is contraindicated in patients who are CYP2C9 poor metabolizers or in individuals using moderate or strong CYP2C9 inhibitors.

Because gastrointestinal perforations have been reported in clinical trials with deuruxolitinib, patients should be promptly evaluated if new onset abdominal symptoms occur. Patients using deuruxolitinib should be monitored for anemia, lipid elevations, lymphopenia, and neutropenia. The use of live vaccines should be avoided during and immediately prior to treatment with deuruxolitinib.

Deuruxolitinib should not be used concomitantly with strong CYP3A4 and moderate or strong CYP2C9 inducers. Based on animal studies, deuruxolitinib may cause fetal harm if used during pregnancy. It should not be used while breastfeeding or in patients with severe hepatic or renal impairment. The most common adverse reactions to deuruxolitinib are acne, anemia, headache, fatigue, herpes, hyperlipidemia, increased blood creatine phosphokinase, increased weight, lymphopenia, nasopharyngitis, neutropenia, skin and soft tissue infections, and thrombocytosis.¹

REFERENCES

1. Leqselvi. Prescribing information. Sun Pharmaceutical Industries, Inc; July 2024. Accessed November 11, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217900s000lbl.pdf

2. Leqselvi Commercial Launch Indefinitely Delayed Due to Patent Ruling. News release. National Alopecia Areata Foundation. November 8, 2024. Accessed December 16, 2024. https://www.naaf.org/news/leqselvi-commercial-launch-indefinitely-delayed-due-to-patent-ruling/

3. US FDA approves Leqselvi (deuruxolitinib), an oral JAK inhibitor for the treatment of severe alopecia areata. News release. Sun Pharma. July 25, 2024. Accessed November 11, 2024. https://sunpharma.com/wp-content/uploads/2024/07/Sunpharma-LEQSELVI-Approval-Scenario-Press-Release.pdf