Twice-Daily Deuruxolitinib Outperformes Once-Daily in Severe AA

Twice-daily dosing of the oral Janus kinase (JAK) inhibitor deuruxolitinib (Leqselvi; Sun Pharmaceuticals) produced roughly 2.5 times the scalp hair regrowth seen with once-daily dosing of the same total drug exposure in adults with severe alopecia areata (AA), according to a phase 2 dose-optimization trial newly published in the Journal of the American Academy of Dermatology.¹ The results, though based on a small patient sample, turned out to matter well beyond the trial itself: they determined the dosing regimen that Sun Pharmaceutical Industries ultimately carried into pivotal phase 3 testing and, in 2024, into FDA approval.²

AA is a chronic autoimmune disease that causes patchy or complete hair loss and, until recently, offered patients few effective treatment options. Deuruxolitinib, an oral selective inhibitor of JAK1 and JAK2, works by blocking downstream signaling of the proinflammatory cytokines thought to drive AA.

An earlier phase 2 dose-ranging study had shown that an 8-mg twice-daily (BID) regimen (16 mg daily total) improved scalp hair regrowth after 24 weeks, but it remained unclear whether that same total dose would work as well if consolidated into a single daily pill, an approach which has the potential to improve medication adherence.

How Twice-Daily Dosing Outperformed Once-Daily

In this randomized, parallel-group, multicenter trial (NCT03811912), investigators assigned adults with severe AA in a 1:1 ratio to deuruxolitinib 8 mg BID (n = 29) or 16 mg once daily (QD; n = 28) for 24 weeks.¹ Patients had a mean baseline Severity of Alopecia Tool (SALT) score of 88.7 out of 100 and the mean duration of the current AA episode was 44.0 months.

At week 24, the mean relative change in SALT score from baseline was 46.4% with 8 mg BID compared with 18.0% with 16 mg QD. More patients on 8 mg BID achieved a SALT score of 20 or less (34.5% vs 10.7%) or 10 or less (20.7% vs 3.6%), thresholds representing 80% and 90% scalp coverage, respectively. Response rates favored BID dosing across every threshold measured, with nearly half of BID patients (48.3%) achieving at least a 50% relative reduction in SALT score, compared with 17.9% of QD patients.

Safety was comparable between arms with treatment-emergent adverse events (TEAEs) occurred in 79.3% of BID patients and 82.1% of QD patients. Most TEAEs were graded mild or moderate. The most common events were upper respiratory tract infection, nasopharyngitis, acne, and headache and matched the known safety profile of oral JAK inhibitors. No serious adverse events, treatment discontinuations due to adverse events, or deaths occurred in either group.

How This Phase 2 Trial Shaped an Approved Therapy

Based on these findings, the study authors selected 8 mg BID for the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, which went on to confirm the regimen's efficacy against placebo and support its FDA approval in July 2024, the third JAK inhibitor cleared for severe AA alongside baricitinib (Olumiant; Eli Lilly) and ritlecitinib (Litfulo; Pfizer).² In THRIVE-AA2, 33.0% of patients receiving 8 mg BID achieved a SALT score of 20 or less at week 24, compared with 0.8% on placebo—outcomes broadly consistent with what this earlier, smaller phase 2 trial had predicted.³

The study's small size and its narrow focus on comparing 2 dosing intervals limit how much can be concluded about deuruxolitinib's broader efficacy and safety profile. Two open-label extension studies are continuing to track the drug's long-term performance; one has completed and the second is ongoing.

“These results may reveal the need for all-day exposure of deuruxolitinib, but, most importantly, the results have important implications for clinical practice and will help guide clinicians and their patients in making treatment decisions for managing AA,” the authors concluded.

References

1. King B, Kempers S, Mesinkovska NA, et al. Dose optimization of deuruxolitinib in adults with alopecia areata: a phase 2 randomized trial. J Am Acad Dermatol. Published online September 2026. doi:10.1016/j.jaad.2026.09.013
2. Santoro C. FDA approves deuruxolitinib for alopecia areata. AJMC®. July 26, 2024. Accessed September 23, 2026. https://www.ajmc.com/view/fda-approves-deuruxolitinib-for-alopecia-areata
3. Jeremias S. Phase 3 data highlight hair regrowth with deuruxolitinib in AA. AJMC. May 28, 2026. Accessed September 23, 2026. https://www.ajmc.com/view/phase-3-data-highlight-hair-regrowth-with-deuruxolitinib-in-aa