Incyte, itching for a piece of Dupixent's market, hits goals in midphase skin disease trial

Incyte has laid down a marker in its pursuit of Regeneron and Sanofi’s Dupixent in prurigo nodularis, linking its oral challenger to significant improvements in itch and disease severity in a phase 2 study.

Investigators randomized 146 adults with prurigo nodularis to receive one of three daily oral doses of the JAK1 inhibitor povorcitinib or placebo. Subjects in the trial, which began before the Dupixent approval, had either had an inadequate response or been intolerant to prior therapy. Incyte revealed the primary endpoint hit last year and shared data at the American Academy of Dermatology Annual Meeting Sunday.

After 16 weeks, 36.1% to 54.1% of patients on povorcitinib had at least a four-point improvement on an itch scale, compared to 8.1% of their peers on placebo. The study showed a dose-dependent increase in the response rate, with the highest, 75 mg dose performing best, and in the time to response. It took a median of 17 days for patients on the high dose to experience a four-point improvement, versus 58 days for the low dose.

Regeneron and Sanofi tracked the effect of Dupixent on the itch scale in their phase 3 program. After 24 weeks, 60.0% and 57.7%, respectively, of patients on Dupixent in the PRIME and PRIME2 trials had (PDF) a four-point or greater improvement. The placebo response rates were 18.4% and 19.5%.

All the studies also looked at the proportion of patients with improved itch and an Investigator’s Global Assessment Treatment Success score of zero or one. At week 16, up to 35.1% of patients on povorcitinib met both criteria, compared to a 2.5% rate in the placebo arm. After 24 weeks, the figures for Dupixent were 38.7% and 32.1%, versus 9.2% and 8.5% for placebo.

With the usual caveat that cross-trial comparisons can be unreliable, particularly when comparing phase 2 data with phase 3 results, the readout suggests povorcitinib may deliver competitive efficacy. Incyte has given up a head start to Dupixent, which won FDA approval in 2022, but the company sees benefits to following rather than leading.

“[Dupixent] has provided us the regulatory pathway on the way to go in terms of itch resolution and skin change resolution. We'll offer the once-daily oral convenience. We think we'll have a really good agent in terms of high efficacy,” Steven Stein, M.D., chief medical officer at Incyte, said on the company’s fourth-quarter results earnings call last month. 

Incyte plans to start its phase 3 prurigo nodularis program this year. The biotech is already running phase 3 trials of its topical ruxolitinib cream in prurigo nodularis. Incyte sees the topical and oral candidates allowing it to treat a broad spectrum, from mild to severe disease, of patients with prurigo nodularis, hidradenitis suppurativa and vitiligo.