Selective JAK Inhibition With Deuruxolitinib Restores Hair Growth in Alopecia Areata

“Deuruxolitinib is an oral JAK inhibitor that treats alopecia areata by blocking the JAK-STAT signaling pathway through selective inhibition of JAK1 and JAK2. Deuruxolitinib reduces the autoimmune attack on the hair follicles, thereby allowing for hair regrowth,” said Vimal Prajapati, MD, FRCPC, DABD, in an interview with Dermatology Times.

Prajapati, a clinical associate professor at the University of Calgary and co-founder and co-director of the Skin Health & Wellness Centre, Dermphi Centre, Dermphi Shop, and Dermatology Research Institute, provided insights into the mechanism of action, clinical trial outcomes, monitoring considerations, and safety profile of deuruxolitinib (Leqselvi; Sun Pharma), an oral JAK1/2 inhibitor approved for severe alopecia areata in adults and recently available in the US.¹

Mechanism of Action

Prajapati first discussed how AA is driven by autoimmune-mediated attack on hair follicles via heightened JAK-STAT signaling. Deuruxolitinib selectively inhibits JAK1 and JAK2, thereby suppressing this inflammatory cascade and enabling hair regrowth.

THRIVE-AA Clinical Trial Outcomes

The pivotal phase 3 THRIVE-AA (NCT04518995; NCT04797650) trials demonstrated meaningful hair regrowth with deuruxolitinib.^2,3 Efficacy was consistent across subgroups regardless of age or disease duration, though patients with shorter disease duration (less than 6 months) exhibited slightly better responses—highlighting the value of early intervention. Comorbidities were controlled for in the trial design, limiting subgroup data in this area.

Monitoring Recommendations

Similar to other oral JAK inhibitors, deuruxolitinib requires baseline and routine laboratory surveillance. According to Prajapati, testing should include CBC with differential, liver enzymes, fasting lipid panel, hepatitis B/C and HIV serologies, and TB testing. Follow-up monitoring is recommended every 3 months, with pregnancy testing in women of childbearing potential. Unique to deuruxolitinib, baseline CYP2C9 genotyping is advised in the US label to exclude poor metabolizers or those on CYP2C9 inhibitors.

Safety and Adverse Events

With the 8 mg twice a day dose, the most frequent adverse events were headache (12%), acne (10%), nasopharyngitis (8%), elevated serum CPK (5%), and weight gain (3%). Thromboembolic events were dose-related: none occurred with 8 mg BID during the initial 52 weeks, though one DVT was later reported in the extension phase. With the 12 mg twice a day dose, 5 thrombotic events occurred within the first 52 weeks, with additional VTEs noted through week 98. Serious infection rates were low at 0.6%, with minimal incidences of HSV (1.8%) and herpes zoster (1.2%). No TB reactivation or major adverse cardiovascular events were observed. Laboratory abnormalities were infrequent, with dyslipidemia (5.8%), anemia (2%), neutropenia (1.3%), and elevated liver enzymes (less than 1%) among the most noted.

References

1. Sun Pharma announces launch of Leqselvi (deuruxolitinib) in the United States for the treatment of severe alopecia areata. News release. Sun Pharmaceuticals Industries. July 14, 2025. Accessed September 2, 2025. https://sunpharma.com/wp-content/uploads/2025/07/AFD_LEQSELVI-Product-Launch-Press-Release_7.14.25.pdf
2. Completed study to evaluate the efficacy and safety of CTP-543 in adults with moderate to severe alopecia areata (THRIVE-AA1). ClinicalTrials.gov. Updated May 3, 2023. Accessed September 2, 2025. https://clinicaltrials.gov/study/NCT04518995
3. Completed study to evaluate the efficacy and safety of CTP-543 in adults with moderate to severe alopecia areata (THRIVE-AA2). ClinicalTrials.gov. Updated July 3, 2023. Accessed September 2, 2025. https://clinicaltrials.gov/study/NCT04797650