After a three-month delay this spring, Incyte has clinched its second dermatology nod for Opzelura. And this time, it’s a historic one.
Late Monday, the FDA gave the all-clear to Opzelura, the sister med to Incyte’s JAK inhibitor Jakafi, for nonsegmental vitiligo in adults and teens ages 12 and older. The green light makes Opzelura the first FDA-approved treatment for repigmentation in vitiligo patients. Additionally, the drug—also known as ruxolitinib cream 1.5%— is the only topical JAK approved in the U.S., Incyte noted in a release.
“Over-activity of the JAK signaling pathway is believed to drive inflammation involved in the pathogenesis and progression of vitiligo,” Incyte noted at last year’s Opzelura priority review announcement.
The med’s vitiligo nod is no doubt a breakthrough for patients, but the indication may only represent a small piece of Opzelura sales for Incyte, worth about $182 million at peak in the U.S., SVB Leerink analysts forecast previously. Meanwhile, the med is well on its way to a vitiligo nod in Europe, which kicked off the formal review process for Incyte’s application in late October.
Opzelura is approved for continuous use on the skin twice a day on affected areas of up to 10% of the body’s surface area, Incyte explained. Patients may need to take the med for at least 24 weeks before seeing satisfactory results, the company pointed out.
Vitiligo is a chronic autoimmune disease that causes depigmentation of the skin from the loss of pigment-generating cells known as melanocytes. The condition is estimated to affect more than 1.5 million people in the U.S., and, prior to Monday’s approval, there were no FDA- or EMA-sanctioned therapies for repigmentation in vitiligo.
Opzelura’s vitiligo green light follows a September 2021 FDA approval in mild to moderate atopic dermatitis. The drug was cleared to treat patients ages 12 and up who aren’t suitable for or have failed on other topical prescriptions.
FDA vitiligo approval was based on data from the phase 3 TRuE-V program, which was conducted in more than 600 nonsegmental vitiligo patients. The primary endpoint for the program was the Vitiligo Area Scoring Index (VASI), a gauge of disease severity that Incyte used to measure improvements in facial and total body repigmentation against a placebo cream.
Two separate phase 3 studies found that at Week 24, roughly 30% of patients given Opzelura hit at least a 75% improvement from baseline on the facial Vitiligo Area Scoring Index (F-VASI75), meeting the trials’ primary endpoint. That compared to 8% and 13% of patients on a dummy cream in the studies TRuE-V1 and TRuE-V2, respectively, Incyte said.
At the one-year mark, roughly 50% of patients on Opzelura hit the studies’ primary endpoint of facial repigmentation.
The most common side effects seen in the trials were application site acne, redness and itchiness, pharynx and nasal cavity inflammation, headache, urinary tract infection and fever.
As a JAK inhibitor, Opzelura carries a boxed warning for serious infections, death and cancer as well as heart-related events and blood clots. It’s important to note that some of those problems are thus far only theoretical for Incyte’s cream, as they’ve only turned up in oral JAK inhibitors, while other issues reflect observations from JAKs for inflammatory conditions.
Opzelura’s vitiligo nod did come a few months later than initially expected, after the FDA in March said it needed extra time to review additional data from the med’s phase 3 studies, which it flagged as a “major amendment.”
While it wasn’t immediately clear what sort of additional information the FDA had requested, the move didn’t seem “indicative of a major concern given Opzelura is still continuing its launch in atopic dermatitis (AD), and all [chemistry, manufacturing and controls] issues should have been addressed during the AD review,” SVB Leerink analysts wrote in a note to clients earlier this year.