The FDA put out a briefing document last week saying it was "conflicted" on Eli Lilly and Incyte's refiled rheumatoid arthritis drug, baricitinib. And the experts on Monday's advisory committee for the drug's application were no different. The expert panel voted 10-5 in favor of the 2-mg dose but flipped those numbers to vote 10-5 against the 4-mg dose.
But even the affirmative votes seemed shaky at best; memorably, one of the panelists said, “I voted yes, I could have definitely voted no."
The sticking point, predictably, was safety. While the panel voted overwhelmingly in favor of the drug's efficacy—14-1 on 2 mg and 15-0 on 4 mg—they split on safety, voting against the 4-mg dose and in favor of the 2-mg dose. But even this wasn't a decisive victory; the votes fell 9-6 thanks to safety concerns, such as pulmonary embolism and deep vein thrombosis, that the FDA took care to lay out.
Specifically, the FDA's presentations focused on the difficulty of assessing the 2-mg dose because of a lack of relevant data relative to the amount of data for the 4-mg dose in the phase 3 program.
"Notably, only 2 of the 4 phase 3 trials included the 2-mg dose, and these allowed patients to be rescued with 4 mg if adequate efficacy was not achieved (since these were likely patients with more active disease, it may have skewed the results for the 2-mg dose)," wrote Leerink analyst Geoffrey Porges in a note.
"Bulls may argue that at least the 2 mg has likely made it through; bears may argue that without the 4-mg dose, the perception and commercial profile of baricitinib is wounded (in the U.S.)," wrote Bernstein analyst Tim Anderson, M.D., in a note.
Even if the 2-mg dose is approved, Anderson went on, it is "not that different" from Pfizer's Xeljanz, with which it would be competing. He sees a difficult path forward for baricitinib as "LLY does not know the RA space, which is crowded; and biosimilars in the RA market are coming (or are here, in the case of Remicade)."
The mixed decision is a blow for Incyte, which earlier this month suffered the flop of the phase 3 trial of its IDO inhibitor epacadostat and Merck's Keytruda in melanoma.