FDA rejects Eli Lilly's ulcerative colitis prospect mirikizumab, citing manufacturing shortfalls

Following the surprise FDA rejection of Alzheimer’s disease candidate donanemab in January, another Eli Lilly biologic drug has been met with an FDA cold shoulder. 

The FDA has declined to approve Lilly’s mirikizumab for the treatment of ulcerative colitis, the company said Thursday.

The drug recently won an approval in Japan for moderate to severe ulcerative colitis, and European approval is expected after drug reviewers at the European Medicines Agency gave a positive opinion for its use in moderate to severe patients who’ve failed or were intolerant to other treatments.

The FDA didn’t raise any concerns about mirikuzmab’s clinical profile or label, Lilly said. Instead, the agency raised issues related to manufacturing.

In a statement to Fierce Pharma, a Lilly spokesperson said the company is working with the FDA to “address and resolve observations” that were noted during a recent pre-approval inspection. Lilly is also discussing next steps with the FDA to understand the time it might need to resolve the FDA’s concern, the spokesperson added.

The FDA recently found several quality control shortfalls at Lilly’s plant in Branchburg, New Jersey, and issued a Form 483 after a 12-day inspection in July, Reuters reported in October. The agency at the time criticized the site for not adequately tracking potentially contaminated drug batches.

Several biologic drugs were implicated in the FDA citation, including migraine drug Emgality and cancer drugs Erbitux and Cyramza.

It’s not clear whether the Branchburg site is the problem behind the mirikizumab rejection.

The FDA complete response letter disrupts Lilly’s plan to introduce a first-in-class med and potential blockbuster in ulcerative colitis. Analysts with Evaluate Vantage, in a recent report, estimated that mirikizumab could reach $1.2 billion sales by 2028.

Mirikizumab is an IL-23 inhibitor. AbbVie’s anti-IL-23 star Skyrizi recently aced a phase 3 trial as an induction therapy in moderate to severe ulcerative colitis. And pending the readout from a maintenance study, AbbVie has said it plans to file for an FDA approval this year.

Johnson & Johnson is also moving along its IL-23 drug Tremfya in the inflammatory bowel disease subtype.

Ulcerative colitis is a highly competitive field. Beyond IL-23 inhibitors, J&J’s IL-12/23 inhibitor Stelara is also approved in the disease. Currently available small-molecule drugs include JAK inhibitors such as AbbVie’s Rinvoq, plus Bristol Myers Squibb’s S1P modulator Zeposia. Pfizer also plans to seek approval for its own S1P drug etrasimod. More drugs are in phase 2 or phase 3 development.

Besides ulcerative colitis, Lilly is also testing mirikizumab in Crohn’s disease, the other IBD subtype, in a phase 3 trial.

Meanwhile, Lilly is awaiting FDA decision on another biologic drug, lebrikizumab, in the inflammatory skin condition of atopic dermatitis. If the two drugs share the same manufacturing site, then Lilly could be in more trouble.