Povorcitinib 75 mg Rapidly Reduces Itch and Hives in CSU, With Jonathan Bernstein, MD

Phase 2 data presented as a late breaker at the 2025 American College of Allergy, Asthma, & Immunology (ACAAI) demonstrated that povorcitinib 75 mg rapidly and safely reduced itch and hives in patients with chronic spontaneous urticaria (CSU).

The phase 2 randomized, double-blind study assessed the efficacy and safety of povorcitinib, a selective kinase 1 (JAK1) inhibitor, in 136 adults with moderate to severe CSU who were ≥ 3 months refractory to second-generation H1 antihistamines. The primary endpoint was the change from baseline in weekly Urticaria Activity Score (UAS7) at week 12. Secondary endpoints included patients who achieved UAS7 ≤ 6 (disease control), patients with UAS7 = 0 (complete response), daily UAS, and safety and tolerability.

Participants were randomized 1:1:1 to placebo (n = 34) or daily povorcitinib, either 15 mg (n = 33), 45 mg (n = 34), or 75 mg (n = 35) for the 12-week placebo-controlled period. Participants on povorcitinib 75 mg had a greater least squares mean (LSM) change in UAS7 from baseline than those on placebo (-23.91 vs -17.90; P =.0470). Moreover, more patients on the 75 mg dose achieved disease control at week 12 (44.1%) than those on placebo (29.4%) or on the 45 mg (44.1%) or 15 mg doses (30.3%).

Compared with placebo (23.5%) and the doses 45 mg (29.4%) and 15 mg (24.2%), more participants on povorcitinib 75 mg became symptom-free at week 12 (42.9%). By day 3, povorcitinib 75 mg showed rapid improvement in daily UAS (mean change from baseline, -1.3 vs -0.7). All povorcitinib doses were well tolerated, with no safety signals.

At ACAAI 2025, HCPLive sat down with Jonathan A. Bernstein, MD, from the University of Cincinnati, to discuss the significance of these findings.

HCPLive: Based on the phase 2 results, how would you characterize povorcitinib’s efficacy across different doses in reducing hives, angioedema, and pruritus compared with placebo?

Bernstein: The data was very interesting. It showed that there was a dose-response improvement in the reduction of hives. This was sustained at different time points, both at week 4, at week 8, and at week 12. However, the placebo also tended to increase a little bit. The effect change was approximately 5.8 points, so there was a significant improvement in urticaria.

There were no unexpected safety signals identified in this population. If you looked at the most common side effects, there may have been some worsening acne, some other minor problems [such as] headache [and] nasopharyngitis.

[We didn’t see] any difference between subgroups, but this was a small study.

HCPLive: How do these findings compare with the efficacy profiles of existing standard-of-care CSU treatments, including antihistamines and omalizumab?

Bernstein: We see a similar response in other therapies. The magnitude of response is comparable. It might be a little lower than what you see with some of the other therapies in terms of UAS7, where people had complete control. It probably wasn't as great a magnitude as other therapies [with reduction in hives], but it was considered statistically significant.

HCPLive: What aspects of the povorcitinib data might warrant caution or closer monitoring?

Bernstein: You would expect that you'd see more separation from placebo at the end of the 12 weeks, and the placebo had a 17.9-point reduction, whereas the active drug 75 mg was [a] 23.9-point [reduction]. That was a little disappointing. It was statistically significant, but not of great magnitude, as you'd expect with others that we've seen with other drugs. Especially in a phase 2 study, you'd expect to see a greater magnitude of an effect.

HCPLive: Is there anything else you would like to highlight about these findings?

Bernstein: JAK inhibitors are an interesting target. There are certainly more downstream in the IgG pathway, and there seems to be an effect. The safety was good, which is encouraging, so I think it is feasible that there could be a role for JAK inhibitors in the management of chronic spontaneous urticaria.

This transcript was edited for clarity.

Relevant disclosures for Bernstein include SANOFI-AVENTIS U.S. LLC, Pharming Healthcare, Inc., Novartis Pharmaceuticals Corporation, BioCryst Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc., Regeneron Healthcare Solutions, Inc., CSL Behring, Blueprint Medicines Corporation, Dermavant Sciences, Inc., Incyte Corporation, Eli Lilly and Company, and GENZYME CORPORATION.

References

Metz M, Bernstein J, Pinter A, et al. EFFICACY AND SAFETY OF POVORCITINIB IN ADULTS WITH CHRONIC SPONTANEOUS URTICARIA: PHASE 2 RESULTS. Annals of Allergy, Asthma & Immunology. 2025;135(5):S3. doi:https://doi.org/10.1016/j.anai.2025.10.020