AbbVie has pegged multibillion-dollar hopes on Rinvoq to fill the revenue gap when immunology superstar Humira loses U.S. market exclusivity. But that plan, dependent on multiple label expansions, has hit its second regulatory setback in weeks.
The FDA has pushed back a decision on an application for Rinvoq in moderate to severe atopic dermatitis by three months, as the agency—which has concerns about the safety of meds in the JAK inhibitor class—needs more time to review additional information the company submitted at its request, AbbVie said Friday. The verdict is now expected early in the third quarter.
The news didn’t come as a surprise. It followed another three-month delay for Rinvoq’s filing in psoriatic arthritis, which the Illinois pharma unveiled mid-March. At the time, AbbVie disclosed that the FDA had requested additional information on the benefit-risk profile for the JAK inhibitor in eczema, too.
In eczema, AbbVie has predicted peak sales of Rinvoq to hit around $2 billion in 2025. The internal estimate came from an investor update in December, when management dialed up its combined peak projection for Rinvoq and fellow immunology rising star Skyrizi to $15 billion after a series of clinical wins for the two meds.
Rinvoq topped Sanofi and Regeneron eczema big shot Dupixent in a phase 3b head-to-head trial. The AbbVie drug helped more patients achieve 75% improvement on an eczema severity scale after 16 weeks, and it also hit several secondary endpoints evaluating its ability to clear skin and reduce itch.
At the time, industry watchers said they expected Rinvoq to be used after Dupixent in practice because of the AbbVie drug’s relatively weaker safety profile, most notably an increased risk of infection. But the FDA’s concern is not about the infection, but about potential heart problems that have been haunting the entire JAK inhibitor drug class.
The FDA’s requests for more data on Rinvoq in eczema and psoriatic arthritis are “essentially identical and are focused solely on the long-term safety data that Pfizer released for Xeljanz in late January,” Mizuho analyst Vamil Divan wrote in a note after talking to AbbVie when the first delay was announced.
Xeljanz, also a JAK inhibitor, was linked to higher risk of cardiovascular events and cancers compared with traditional TNF inhibitors—such as Humira—in a post-marketing rheumatoid arthritis trial required by the FDA. The study was carried out in a group of high-risk patients. Before that, the FDA first noted problems with a high dose of Xeljanz in 2019 and immediately slapped a restriction on that use.
The agency is now weighing whether to take further action against the Pfizer drug, given the final analysis showed risks for both doses tested. And as Divan views it, the agency might be looking at the Xeljanz issues as a potential class effect.
Before the Xeljanz debacle, the agency had already rejected Gilead Sciences’ JAK inhibitor filgotinib in rheumatoid arthritis, though mainly on the drug’s sperm toxicity. Eli Lilly’s JAK drug Olumiant carries a black box warning covering serious infections, lymphoma and other malignances, and blood clots.
Rinvoq, in its currently approved rheumatoid arthritis indication, also bears a boxed warning about those same safety problems mentioned on Olumiant's label—and that’s for a 15-mg once-daily dose. For eczema, AbbVie is seeking a green light for a 30-mg dose, and the drug’s recent clinical win in ulcerative colitis features a 45-mg version.
The fact that AbbVie’s only pegging $2 billion in peak sales for Rinvoq in an eczema market worth more than $10 billion is evidence that AbbVie expects challenges advancing the higher 30-mg dose, SVB Leerink analyst Geoffrey Porges said in a note in December.
In a separate report in December, Porges noted that results for 15-mg Rinvoq weren’t shared in the top-line eczema trial announcement despite the drug showing fairly robust efficacy in two earlier pivotal trials. “If the 15-mg dose failed to match Dupixent’s efficacy it will be a liability for AbbVie should the FDA impose their usual restrictions on higher doses of JAK inhibitors,” he said at the time.