Incyte's Opzelura clears skin in children with atopic dermatitis, but safety remains a question

Fighting for a place in the competitive atopic dermatitis market, Incyte hopes to reach younger patients with its JAK inhibitor cream Opzelura. A new pivotal trial win may help the company reach that goal, but safety concerns may present a challenge in a forthcoming market clash.

In a phase 3 trial in children ages 2 to 11 with atopic dermatitis, Opzelura cleared skin in significantly more patients than a nonmedicated topical control did, Incyte said Tuesday. The drug, a topical version of the ruxolitinib ingredient used in Jakafi, is currently approved in eczema patients 12 and older.

The trial, called TRuE-AD3, showed that Opzelura takers had a better chance at achieving clear or almost clear skin with at least a two-point improvement on the Investigators’ Global Assessment Treatment Success (IGA-TS) score at the eighth week. The trial, therefore, hit its primary endpoint.

The readout comes a few weeks after Roivant Sciences’ Dermavant said its rival cream Vtama hit the goals of two phase 3 atopic dermatitis trials in patients as young as 2. Arcutis Biotherapeutics also recently touted a win for its Zoryve cream in two phase 3 trials in eczema patients 6 years of age and older, with a separate study in children ages 2 to 5 expected to report topline data later this year.

In Opzelura’s case, a JAK classwide box warning could be a heavy cross to bear.

When approving Opzelura for eczema in 2021, the FDA slapped a box warning on the topical drug’s label. The warning discusses increased cardiovascular disease risks, serious infections and other side effects that were observed in studies of oral JAK inhibitors.

For the original approval in patients 12 years and above, Opzelura is made of 1.5% ruxolitinib and given twice daily. For the TRuE-AD3 trial in younger patients, Incyte tested both that dose and a lower 0.75% strength.

The company didn’t share specific efficacy or safety data but said the drug’s overall safety profile is “consistent with previous data” with no new safety signals observed. The trial remains ongoing to collect long-term safety data.

Incyte will discuss the data with regulatory agencies to determine the next steps, Jim Lee, M.D., Incyte’s VP for inflammation & autoimmunity, said in a statement Wednesday. By the company’s estimates, eczema affects about 2 million to 3 million children ages 2 to 11 and more than 21 million people 12 years and older.

Meanwhile, Incyte's Opzelura could use a market expansion. The drug’s sales disappointed in the first quarter, coming in at $57 million, or an 8% sequential decline. At that time, Leerink Partners analysts noted that Vtama and Zoryve are expected to enter the eczema market by the second half of 2024. These two drugs don’t have box warnings in their approved plaque psoriasis uses.

Incyte has also been suffering from a high discount rate for Opzelura at around 50% to 60% as of the first quarter. Payers could leverage the potential competition to push for bigger discounts, the Leerink team said in a May note.

Opzelura at the 1.5% strength currently boasts the strongest efficacy data among the three agents, although cross-trial comparisons can be problematic, the Leerink team noted in a May report. Vtama’s data across a wider age group looked comparable to Opzelura at the 0.75% strength in the previous TRuE-AD trials in older patients.

After Vtama’s readout, Leerink analysts put the Dermavant drug’s peak U.S. sales at above $1.5 billion. By comparison, the team figured Opzelura could reach global peak sales of $721 million.