Upadacitinib (Rinvoq, AbbVie) achieved the primary endpoint in the second of two pivotal studies in patients with severe alopecia areata (AA), according to new topline results from the Phase 3 UP-AA clinical program.
The study evaluated the safety and efficacy of upadacitinib 15mg and 30mg, taken once daily, in adult and adolescent patients with severe AA with a mean baseline Severity of Alopecia Tool (SALT) score of 84.0 (approximately 16% scalp hair coverage).
Achieved Endpoints
In Study 1, both doses of upadacitinib achieved the primary endpoint, with 45.2% and 55.0% of patients treated with upadacitinib 15mg and 30mg, respectively, reaching 80% or more scalp hair coverage (SALT score ≤ 20) at Week 24, compared to 1.5% of patients receiving placebo. (These results are consistent with the topline results previously announced from the first parallel replicate study (Study 2) of the Phase 3 UP-AA clinical program.)
Fully 35.2% and 45.8% of patients treated with upadacitinib 15mg and 30mg, respectively, reached 90% or more scalp hair coverage (SALT ≤ 10), compared to 0.7% of patients receiving placebo at Week 24. Additional key secondary endpoints that were met included percentage of subjects with improvements in eyebrows and eyelashes, as well as the percentage of subjects with complete scalp hair coverage (SALT=0) with both doses of upadacitinib at week 24.
Encouraging Results
“People living with AA often face considerable uncertainty related to both the severity and duration of hair loss, despite current treatment options,” says Arash Mostaghimi, MD, MPA, MPH, Associate Professor of Dermatology and Vice Chair of Clinical Trials and Innovation at Brigham & Women’s Hospital and Harvard Medical School in Boston, MA. “These encouraging results are consistent with and reinforce the outcomes observed in the first pivotal trial. Together, these findings underscore the potential of upadacitinib to provide meaningful hair regrowth, offering hope for those enduring the psychosocial burden associated with this disease.”
The safety profile of both doses of upadacitinib in the 24-week, placebo-controlled period (Period A) was generally consistent with that observed in approved indications. Treatment-emergent serious adverse events occurred in 1.9% and 1.8% of patients in the upadacitinib 15mg and 30mg groups, respectively, and 0.7% in the placebo group. Discontinuations due to treatment-emergent adverse events (TEAEs) occurred in 1.1% and 1.5% of patients in the upadacitinib 15 mg and 30 mg groups, respectively, and none in the placebo group.
The most common TEAEs observed were upper respiratory tract infection, acne, increased blood creatine phosphokinase, and nasopharyngitis. Serious infections were reported infrequently, with one in the placebo group, one in the upadacitinib 30mg group, and none in the upadacitinib 15mg group. No adjudicated MACE, adjudicated venous thromboembolic events or deaths were reported. One malignancy (breast cancer) was reported in the upadacitinib 15mg group.
More About UP-AA Clinical Trial
UP-AA M23-716 was conducted as a single protocol that includes two replicate pivotal studies (Study 1 and Study 2) with randomization, investigative sites, data collection, analysis and independent reporting for each study. The Phase 3 randomized, placebo-controlled, double-blind studies evaluate efficacy and safety of upadacitinib in adult and adolescent subjects with severe alopecia areata.
In Study 1 and Study 2 Period A, participants were randomized to one of three groups to receive upadacitinib 15mg, upadacitinib 30mg, or placebo for 24 weeks. In Study 1 and Study 2 Period B, participants originally randomized to upadacitinib dose groups in Period A continued their same treatment in Period B for 28 weeks. Participants originally randomized to placebo in Period A either remained on placebo in Period B, or were randomized in one of two groups, based off of their SALT score at week 24.
In total, Study 1 and Study 2 Periods A and B spanned 52 weeks. Participants who completed Study 1 or Study 2 joined Study 3 and were re-randomized to receive one of two doses of upadacitinib for up to 108 weeks. The two trials randomized 1,399 participants with severe AA aged 12 to 64 across 248 sites worldwide.
