Dive Brief:
- Briefing documents released by the Food and Drug Administration ahead of an April 23 Advisory Committee meeting do not look particularly positive for Eli Lilly & Co. and Incyte Corp.'s rheumatoid arthritis drug baricitinib.
- Questions to be posed to the panel raise concerns about both the safety and efficacy of the drug at the 4 mg dose and the 2 mg dose, as well as if further clinical trials are needed.
- The Janus kinase (JAK) inhibitor, which would be marketed under the brand name Olumiant if approved, was first rejected by the FDA in April 2017 due to a lopsided risk/benefit profile created by safety issues related to thrombosis.
Dive Insight:
While baricitinib was once expected to be Lilly's next blockbuster, the Complete Response Letter it received last year initially made it seem like all hope was lost. But an about-face by the FDA allowed the company to resubmit the drug without conducting further clinical trials, thus saving Lilly millions of dollars and preventing a likely two-year delay to market.
Now Lilly, and partner Incyte, are seeking approval for both — or either — the 4 mg or 2 mg dose of the drug.
Perhaps problematically, the 4 mg dose has been more widely tested and shown greater efficacy, but also seemed to have greater risk of serious adverse events like thrombosis. Yet the questions posed in the FDA briefing documents indicate that the agency is looking to see if there is enough evidence that the drug is safe and efficacious at either dose.
The April 23 meeting is not likely to go well for the companies. Even so, the FDA is not beholden to the decisions of its panels, and while it usually follows the advice of its experts, the agency has been known to make contrary decisions from time to time.
"Overall, the additional data provided in the resubmission did not substantially alter the efficacy and safety data in the original submission. Thus, questions remain regarding the benefit/risk assessment of baricitinib for RA patients," wrote agency reviewers.
From what the documents say, it appears the big issue will be whether the 2 mg dose is approvable.
"Since most of the safety data are with the 4 mg dose of baricitinib and there are limited placebo control data, interpretation of the safety data is challenging, particularly when events continue to accrue in patients treated with open-label baricitinib. This raises the question of whether the 2 mg dose has a favorable benefit/risk profile; however, an important issue is whether there is sufficient safety data to inform the benefit/risk assessment of the baricitinib 2 mg dose."
A negative panel might not just mean another rejection for the drug, but the need for further clinical trials should Lilly and Incyte plod forward with eventual approval.
It remains to be seen whether Lilly would be willing to make further investment if the panel doesn't vote in its favor.
"There will need to be further safety data generated to understand the thrombosis risk for baricitinib, and it would be reasonable to obtain the data and address this safety risk pre-approval," wrote Badrul Chowdhury, director of the FDA's Division of Pulmonary, Allergy, and Rheumatology Products. (In a happy bit of fortune for Lilly, Chowdhury accepted a job this month at AstraZeneca plc and will not likely be part of the drug's review.)