The application is based on phase 3 UP-AA trial data showing significant hair regrowth in patients with severe alopecia areata.
AbbVie
"In the UP-AA clinical program, upadacitinib showed early and substantial scalp hair growth, including complete scalp hair coverage, which is a significant outcome for those living with this often-overlooked disease," said Kori Wallace, MD, PhD, vice president and global head of immunology clinical development at AbbVie, in the news release.¹
The submission, if approved, would make upadacitinib the fourth JAK inhibitor indicated for AA in the US. Baricitinib (Olumiant; Eli Lilly) received FDA approval for severe AA in adults in
The UP-AA program consisted of 2 replicate studies conducted under a single protocol, each with independent randomization, sites, and analysis. Period A was a 24-week double-blind, placebo-controlled phase, followed by Period B, a blinded extension through week 52. Patients were randomized to upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily.¹
The enrolled population had substantial disease burden, with a mean baseline SALT score of 84; approximately 51% of participants had a SALT score of 95 or higher, indicating near-total or total scalp hair loss.¹
At week 24, the primary end point of SALT score 20 or lower (representing ≥80% scalp hair coverage) was achieved by 45.2% and 44.6% of patients receiving upadacitinib 15 mg in studies 1 and 2, respectively, compared with 1.5% and 3.4% in placebo groups. The 30-mg dose yielded responses of 55.0% and 54.3%. These responses continued to improve through week 52, with SALT 20 or lower rates reaching approximately 55% to 64% across both doses.¹
Complete scalp hair regrowth (SALT = 0) at week 24 was achieved by 14.1% and 13.1% of patients on the 15-mg dose and 20.3% and 22.5% on the 30-mg dose, compared with 0% and 0.7% on placebo. By week 52, complete regrowth rates rose to approximately 27% to 37% across doses.¹
“The UP-AA phase 3 findings highlight upadacitinib’s potential as a best-in-class, once-daily, JAK1 selective inhibitor for alopecia areata, delivering the highest levels of scalp hair regrowth reported to date in a pivotal trial, with many patients reaching near-complete or full coverage within 24 weeks,” Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine in New Haven, Connecticut, and editor in chief of Dermatology Times, said in a
The safety profile through week 52 was reported to be consistent with observations at week 24 and with upadacitinib's known safety profile across its approved indications.¹ Upadacitinib carries boxed warnings for infections, malignancy, major adverse cardiovascular events, thrombosis, and mortality, consistent with boxed warnings in most JAK inhibitors, however, not a major cause for concern in dermatology patients.5
Alopecia areata affects approximately 2% of the global population, with severe forms causing profound psychosocial impact.6 Prior to baricitinib's 2022 approval, no systemic therapies were specifically indicated for AA, leaving a significant treatment gap, particularly for patients with extensive hair loss. While baricitinib demonstrated efficacy in the BRAVE-AA1 (
Possible limitations include that the week 52 data from Period B are descriptive rather than controlled, as placebo comparisons ended at week 24. Long-term durability of response and comparative efficacy vs other approved JAKs are data points that could be explored in future readouts. The application is also under review by the European Medicines Agency. An ongoing extension study (Study 3) will provide data through approximately 108 weeks.¹
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