As Incyte strives to push its topical JAK inhibitor Opzelura into additional dermatology indications, the company’s latest data drop in prurigo nodularis carries a mix of both positives and negatives.
Given the mixed-bag results, Opzelura’s future in the chronic skin disease has become murky, multiple analysts said over the weekend.
In tandem with the annual meeting of the American Academy of Dermatology (AAD) in Orlanda, Florida, Incyte on Saturday rolled out data from two parallel phase 3 trials assessing Opzelura in prurigo nodularis (PN), which is characterized by intense itch and thickened red bumps on the arms, legs and torso.
While the first study, TRuE-PN1, met its primary endpoint and all key secondary endpoints, the second trial, TRuE-PN2, did not reach statistical significance on its primary endpoint despite the numbers favoring Opzelura overall, Incyte said in a release.
Although a pooled analysis of the two trials remained positive, the “lack of consistency in statistical significance” between the parallel studies “creates uncertainty in the path forward for Opzelura in PN,” analysts at Leerink Partners wrote in a note to clients on Sunday.
Incyte said it will talk to regulators about Opzelura in PN. But given the miss in the TRuE-PN2, the Leerink team figures Incyte may be put on the hook to run an additional clinical trial in the potential indication.
Analysts at William Blair also argued in a Monday note that “the regulatory path ahead is unclear for Opzelura in PN.”
“It now seems like an uphill battle for Opzelura to gain approval in PN given the mixed results, but we await additional feedback from regulators and the company on the next steps,” the William Blair team said.
Recent biologics approvals in PN, including those for Sanofi and Regeneron’s Dupixent and Galderma’s Nemluvio—neither of which are topical treatments—were supported by two positive pivotal studies, both of which met all main and secondary endpoints, the William Blair team pointed out.
Digging deeper into the positive TRuE-PN1 results, twice daily Opzelura—also known as ruxolitinib cream 1.5%—helped 44.6% of adults with PN achieve a four-point or greater improvement from baseline on the Worst-Itch Numeric Rating Scale (WI-NRS4) versus just 20.6% of patients who received a dummy cream at the study’s 12-week mark.
Opzelura also led to significant itch improvements compared to a vehicle cream at day 7 of the trial, with numerical improvements versus the control reported at earlier points in time, Incyte explained.
The drug also knocked out all key secondary endpoints in the trial, the company added.
As for the TRuE-PN2 readout, Opzelura showed a “strong positive trend” across all key secondary endpoints and was favored versus a dummy cream on the study’s primary efficacy benchmark—again utilizing the WI-NRS4—though the drug fell short of achieving statistically significant results, Incyte said.
As Incyte’s blockbuster JAK inhibitor Jakafi edges toward a patent cliff, the Wilmington, Delaware-based drugmaker has been increasingly emphasizing the importance of Opzelura.
Aside from a potential nod in PN, Incyte is also studying its topical JAK inhibitor in the abscess-causing inflammatory skin condition hidradenitis suppurativa and angling for an atopic dermatitis expansion into pediatric patients.
While the mixed results in PN likely aren’t the news Incyte was hoping for, the indication is relatively small for Opzelura. Hidradenitis suppurativa, for which Opzeulra expects a phase 3 readout in the first half of 2025, represents a much greater opportunity, the William Blair analysts noted.
In 2024, Opzelura grew sales 50% to $508 million for the entire year. The drug is currently approved in atopic dermatitis, also known as eczema, as well as vitiligo.
Looking ahead, Incyte expects 2025 Opzelura sales to come in between $630 million and $670 million.