The entire JAK inhibitor family of medicines is feeling the ripple effects from a safety signal flagged for Pfizer’s Xeljanz. Now, the first marketed drug in the class is encountering increased scrutiny from the FDA.
The FDA has pushed back a decision for Incyte’s application for Jakafi in steroid-refractory chronic graft-versus-host disease (GVHD) by three months, the company said Tuesday. The new target action date is Sept. 22.
The delay came after Incyte submitted additional data in response to a recent request by the agency. The FDA views the update as a major amendment to the previous package, so it now needs more time to review it, the drugmaker said.
Despite the setback, RBC Capital Markets analyst Brian Abrahams still believes Jakafi will eventually get its approval. Feedback from experts has been positive, “with physicians noting limited alternatives and clear signs of efficacy for the drug,” he wrote in a Wednesday note to clients. He projects the indication could get Jakafi over $300 million in U.S. peak sales.
Jakafi is only the latest in the JAK drug class to face an FDA delay. Previously, the FDA postponed its verdict on Eli Lilly’s Incyte-partnered Olumiant and Pfizer’s investigational abrocitinib in moderate-to-severe atopic dermatitis. The agency also held up Xeljanz’s filing in ankylosing spondylitis by three months. Before that, the agency delayed two AbbVie filings for Rinvoq in eczema and psoriatic arthritis.
The extra hurdles stemmed from a safety problem observed in a post-marketing trial of Xeljanz in rheumatoid arthritis. The study linked an increased risk of dangerous heart-related side effects to the Pfizer JAK inhibitor compared with traditional TNF blockers in patients who were at least 50 years old with at least one existing cardiovascular risk factor.
Jakafi was the first JAK inhibitor to reach the market with an FDA go-ahead for the bone marrow disease myelofibrosis in late 2011. The drug has been allowed in patients with steroid-refractory acute GVHD since May 2019.
The company's latest application in chronic GVHD comes off positive results from the phase 3 REACH3 trial. At week 24, the drug triggered a response in 49.7% of patients. For patients on best available treatments, 25.6% responded.
“We remain confident in the data from the REACH3 trial supporting our sNDA submission for [Jakafi] and look forward to continued dialogue with the FDA throughout the remainder of the review process,” Incyte’s chief medical officer, Steven Stein, M.D., said in a statement.
Currently, Jakafi is given at different strengths twice daily. Incyte is evaluating a once-daily formulation with a potential approval expected by the end of 2022.
In a more important regulatory decision for Incyte, the company is also awaiting a verdict for a cream product with the same ruxolitinib active ingredient as used in the oral Jakafi for the treatment of atopic dermatitis. It used a priority review voucher for that application to secure an early decision date that’s scheduled for June 21.
An Incyte spokesperson confirmed that the application for the topical drug remains under review at the FDA, though RBC’s Abrahams said he now sees “incrementally higher risk for a clean label.” Last month, when asked about the increased JAK scrutiny at the FDA, Stein said the company is “very comfortable where we are with the review.”
Editor's Note: The story has been updated with analysis from RBC Capital Markets and a response from Incyte.