FDA pushes eczema decision for Eli Lilly's Olumiant, Pfizer's abrocitinib back 3 months — raising more questions for the JAK class
The FDA review extensions for JAK inhibitors are stacking up.
After Eli Lilly and Incyte disclosed late Tuesday that their supplemental NDA for Olumiant in moderate to severe atopic dermatitis was hit with a 3-month delay, Pfizer revealed early Wednesday that its experimental abrocitinib is meeting the same fate. With Olumiant, the agency needed time to “review additional data analyses submitted by Lilly in response to recent information requests from the FDA,” according to a statement. Pfizer didn’t specify a reason in its release.
In addition, the agency is also knocking back by 3 months a review of Pfizer’s Xeljanz for the treatment active ankylosing spondylitis.
The setback puts Lilly and Pfizer in the same boat as AbbVie, which revealed days ago that regulators asked for an updated benefit-risk profile of its JAK inhibitor Rinvoq, pushing their PDUFA date to Q3 of 2021.
Safety concerns with JAK inhibitors are not new. In fact, following a rocky development path that involved an initial rejection and restrictions in dosing, Olumiant’s initial approval in rheumatoid arthritis came with black box warnings on heightened risks for serious infections, malignancy and thrombosis. Rinvoq sports a similar label.
The issues came to the fore again earlier this year, when Pfizer announced that its drug, Xeljanz, has failed the six-year safety study mandated by the FDA.
Across 4,362 patients, those who received either a low or high dose of Xeljanz experienced more major cardiovascular events — such as stroke and heart attack — than those on Humira or Enbrel. They also had higher rates of cancer, with Pfizer failing to hit non-inferiority on both primary endpoints.
Ilya Yuffa, president of Lilly Bio-Medicines, says they stand by the efficacy of Olumiant. The drug had scored wins in multiple late-stage studies in atopic dermatitis, beating corticosteroids and placebo in clearing eczema.
More recently, it’s also gained prominence as the FDA granted emergency use authorization to a combination of Olumiant and Veklury (remdesivir) for hospitalized Covid-19 patients who need supplemental oxygen, ventilators or life support.
But its utilization in atopic dermatitis has always been questioned. SVB Leerink analyst Andrew Berens previously predicted that it will play a “minor role” in the disease:
Given the dominance of (Regeneron’s) Dupixent in the moderate and severe AD market and known safety risks of infections, malignancies, and thrombosis with oral JAK inhibitors, we believe oral, systemic JAK inhibitors may not capture a meaningful portion of the AD market. While this profile represents limitations of the JAK class for systemic therapy, we believe this could open the door for a greater role for topical JAK usage, which could be prescribed in conjunction with non-JAK systemic treatment.
Incyte, which had initially come up with the drug and allied with Lilly in exchange for $90 million upfront back in 2009, has pulled out of co-funding the development but continues to be eligible for royalties on sales.