[Updated 4/14/17, 2:51 pm. See below.] In a surprise decision, the FDA has declined to approve an experimental rheumatoid arthritis (RA) treatment from Eli Lilly and Incyte, dealing a setback to a drug that is already approved in Europe and was expected to pass muster with U.S. regulators.
Eli Lilly (NYSE: LLY) and Incyte (NASDAQ: INCY) said on Friday that the companies received a letter from the FDA stating that the application for the drug baricitinib (Olumiant) cannot be approved in its current form. Such correspondence between the FDA and companies is typically never made public. But Indianapolis-based Lilly and Incyte, headquartered in Wilmington, DE, say the letter indicated that the FDA wants to see more clinical data “to determine the most appropriate doses.” They also say the FDA asked for more data “to characterize safety concerns across treatment arms.”
Patients feel rheumatoid arthritis pain from inflammation in their joints, but the disease is an autoimmune disorder, meaning it’s the product of an abnormal reaction from the body’s own defenses. The immune system mistakenly attacks the joints, causing swelling in the tissue that lines the inside of joints, according to the Arthritis Foundation. Baricitinib is a once-daily pill called that blocks two Janus kinase (JAK) enzymes, proteins implicated in the development of inflammation. The drug is what’s called a JAK inhibitor.
The Lilly and Incyte collaboration on baricitinib dates to 2009, when Lilly paid Incyte $90 million for rights to develop the drug for inflammatory and autoimmune diseases. The two began developing bacritinib for rheumatoid arthritis a year later. The drug is also currently in mid-stage clinical trials for atopic dermatitis and lupus, and could begin a Phase 3 study in psoriatic arthritis later this year.
In rheumatoid arthritis, Lilly and Incyte tested baricitinib in four Phase 3 clinical trials, including one that compared the drug to adalimumab (Humira), the blockbuster injectable biologic from AbbVie (NYSE: ABBV). Baricitinib beat the AbbVie drug in the head-to-head trial, according to results published in the New England Journal of Medicine in February. Those results showed that 70 percent of patients treated with the Lilly and Incyte drug showed improvement in joint swelling and other criteria established by the American College of Rheumatology, compared to 61 percent of patients treated with the AbbVie drug.
Lilly and Incyte reported that side effects were more common in older patients on bacritinib, with the most frequent problems being bronchitis and inflammation of the mucous membranes. Still, this didn’t lead to a big difference in dropout rates between treatment groups.
An FDA ruling was originally expected early this year, but in January the agency extended the decision deadline by three months to allow for more time to review additional data. Lilly submitted that data, but did not say at the time what additional information the FDA was seeking. One month later, regulators in Europe approved baricitinib for adults with moderate-to-severe active rheumatoid arthritis who haven’t responded to, or can’t take other drugs approved to treat the disease.
[Paragraph added to include analyst comments.] Evercore ISI analyst Umer Raffat was optimistic, predicting in a research note that the drug should eventually win approval despite Friday’s “clear delay.” Still, he speculated that the FDA may want more data on a lower (2 mg) dose than the one used in the head-to-head study between bacritinib and adalimumab (4 mg). If that’s the case, that might be problematic, given it’s unclear if a lower dose of bacritinib is superior to AbbVie’s treatment, Raffat wrote. “There is a lot of evidence [in clinical testing] that implies 4 mg was the more appropriate dose,” he wrote.
The European Medicines Agency approved both doses, with the caveat the 2 mg dose might be more appropriate for some patients, such as those older than 75 who also have a history of infections.
In a prepared statement, Christi Shaw, president of Lilly Bio-Medicines, said the companies disagree with the FDA’s conclusions on baricitinib.
“We are disappointed with this action,” Shaw said. “We remain confident in the benefit/risk of baricitinib as a new treatment option for adults with moderate-to-severe RA.”