Shares of Incyte (INCY) are sinking on Wednesday after the company's Opzelura cream was approved by the U.S. Food and Drug Administration for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis. The approval, however, came with boxed warnings for serious infections, increased risk of heart attack, stroke or cardiac death.
FDA APPROVAL: On Tuesday after the market close, Incyte announced that the FDA approved Opzelura, or ruxolitinib, cream for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis, also known as eczema, in non-immunocompromised patients 12 years of age and older. The ruxolitinib cream is the first topical JAK inhibitor, a class of treatments that work by blocking inflammation-causing enzymes Janus kinases, to be approved in the U.S., Incyte stated.
The FDA approval was based on data from the TRuE-AD clinical trial program, consisting of two randomized, double-blind, vehicle-controlled Phase 3 studies evaluating the safety and efficacy of Opzelura in more than 1,200 adolescents and adults with mild to moderate AD. Results from the studies showed patients experienced significantly clearer skin and itch reduction when treated with Opzelura cream 1.5% twice daily, compared to vehicle.
“The approval of Opzelura is an important advancement in the treatment of AD, and we are pleased to offer a novel topical treatment option that targets a pathway believed to be a source of inflammation,” said Hervé Hoppenot, Incyte's chief executive officer. “At Incyte, we are committed to transforming the treatment of immune-mediated dermatologic conditions like AD. We look forward to bringing Opzelura to the patient community and also continuing to explore its potential in other challenging skin diseases.”
WHAT'S NOTABLE: The label carries the FDA's JAK-class warning for serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis seen with JAK inhibitors for inflammatory conditions.
The FDA previously asked Pfizer (PFE), Eli Lilly (LLY) and AbbVie (ABBV) to include information about the risks of serious conditions and death from the use of their drugs that are in the same class of JAK inhibitors. Initial results from a February trial showed an increased risk of serious heart-related problems and cancer with Pfizer's arthritis drug Xeljanz. The FDA said Eli Lilly's Olumiant and AbbVie's Rinvoq have similar operating mechanisms, leading to the possibility of risks seen in the Xeljanz safety trial.
ANALYST COMMENTARY: William Blair analyst Matt Phipps said that the FDA’s concerns have gone beyond just a black box warning for Opzelura, with the label not only including the same black box warning, but also specifically saying the approval is for short-term and non-continuous chronic use. While the analyst thinks the data to-date strongly supports the risk/benefit of Opzelura, the added warnings and restrictions are sure to give many physicians pause, creating headwinds for commercial adoption, he argues.
Meanwhile, Stifel analyst Stephen Willey said that while the issuance of the boxed warnings was largely in-line with expectations given both FDA's caution and recently published data suggesting the variability of topical ruxolitinib exposure surpassed the IC50 range for both Phase 3 doses at essentially all evaluated time points, he believes the reality of this product label will now amplify the “show me” commercialization story set to unfold here and likely raise additional questions regarding the longer-term ROI associated with the recently-initiated Phase 3 development program in pediatric patients for whom these Boxed Warnings may prove a source of even greater hesitancy amongst prescribers/parents.
PRICE ACTION: Incyte shares are down 7% in Wednesday morning trading to $70.67.
