Pharm'Up 
AbbVie has released encouraging topline results from Study 2 of the Phase 3 UP-AA clinical program, assessing the efficacy and safety of upadacitinib (RINVOQ®) at 15 mg and 30 mg doses, administered once daily, for adults and adolescents with severe alopecia areata (AA). Patients had an average baseline SALT score of 83.8, reflecting approximately 16% scalp hair coverage.
In the study, both doses of upadacitinib met the primary endpoint, with 44.6% of patients on 15 mg and 54.3% on 30 mg achieving 80% or more scalp hair coverage (SALT score ≤ 20) by week 24, compared to just 3.4% of those on placebo (p<0.001).
Kori Wallace, M.D., Ph.D., vice president and global head of immunology clinical development at AbbVie, noted, “Often misjudged as a cosmetic concern, AA is a systemic immune-mediated condition that can lead to complete hair loss on the scalp, eyebrows, and eyelashes. The UP-AA program marks the first pivotal effort to achieve the stringent SALT=0 standard, signifying full scalp hair regrowth. These findings highlight AbbVie’s dedication to developing innovative treatments that can enhance the lives of those with immune-mediated conditions.”
Additionally, 36.0% of patients on 15 mg and 47.1% on 30 mg achieved 90% or more scalp hair coverage (SALT ≤ 10) by week 24, compared to 1.4% on placebo (p<0.001). Other key secondary endpoints were also met, including improvements in eyebrow and eyelash growth, as well as complete scalp coverage (SALT=0) with both doses at week 24.
Arash Mostaghimi, M.D., M.P.A., M.P.H., associate professor of dermatology and vice chair of clinical trials and innovation at Brigham & Women’s Hospital, Harvard Medical School, commented, “The sudden and unpredictable hair loss experienced by those with AA can deeply affect their self-esteem and mental health. There is a critical need for treatments that promote regrowth of both scalp and non-scalp hair. These results suggest upadacitinib could become a valuable new option.”
During the 24-week placebo-controlled period (Period A), the safety profile of both upadacitinib doses was consistent with that seen in approved uses. Serious adverse events occurred in 1.4% of the 15 mg group and 2.8% of the 30 mg group, with no such events in the placebo group. Discontinuations due to adverse events were 0.7% (15 mg) and 1.4% (30 mg), with none in the placebo group. The most frequent treatment-emergent adverse events included acne, nasopharyngitis, and upper respiratory tract infections. Serious infections were rare, at 0.7% (15 mg) and 1.0% (30 mg), with none in the placebo group. No adjudicated major adverse cardiovascular events (MACE), malignancies, or deaths were reported, though one adjudicated venous thromboembolism occurred in the 15 mg group in a patient with multiple risk factors.
About the UP-AA Clinical Trial
The UP-AA M23-716 trial comprises two independent pivotal studies (Study 1 and Study 2) under a single protocol, featuring randomization, separate investigative sites, data collection, analysis, and reporting. These Phase 3, randomized, placebo-controlled, double-blind studies assess upadacitinib’s efficacy and safety in individuals with severe AA. In Period A of both studies, participants are assigned to receive either upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 24 weeks. In Period B, those originally on upadacitinib continue their dose for 28 weeks, while placebo participants either remain on placebo or are reassigned based on their week 24 SALT score. The combined Periods A and B span 52 weeks, with an option for participants to join Study 3 for up to 108 weeks on one of two upadacitinib doses.
About RINVOQ
Developed by AbbVie scientists, RINVOQ is a JAK inhibitor under investigation for various immune-mediated inflammatory diseases. In cellular assays, it more potently inhibits JAK1 and JAK1/JAK3-mediated STAT phosphorylation than JAK2/JAK2-mediated phosphorylation. The specific impact of inhibiting these JAK enzymes on therapeutic effectiveness and safety remains unclear.
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