Delayed FDA reviews may signal trouble for JAK inhibitors in autoimmune space, says GlobalData

Five delays in regulatory reviews for a single drug class in less than one month could serve as an early warning sign that the Food and Drug Administration (FDA) is cracking down on safety signals in Janus kinase (JAK) inhibitors and will continue to keep a close eye on these drugs, says GlobalData, a leading data and analytics company.

The drugs that have been delayed include AbbVie’s Rinvoq (upadacitinib) for psoriatic arthritis (PsA) and atopic dermatitis (AD), Eli Lilly and Incyte’s Olumiant (baricitinib) for AD, and Pfizer’s Xeljanz (tofacitinib) and abrocitinib for ankylosing spondylitis (AS) and AD, respectively.

Heather Leach, PhD, Director of Immunology at GlobalData, comments: “The JAK class of drugs has had a checkered history in autoimmune diseases from the start, with the FDA requiring more data on Pfizer’s Xeljanz for rheumatoid arthritis (RA) in 2012 during the first-ever review of a JAK inhibitor in an autoimmune disease. Concerns over the risk-benefit profile for the higher dosages of these drugs has been a recurring theme. Following this was concern for Galapagos/Gilead’s Jyseleca (filgotinib) with respect to testicular toxicity, and more recently, post-marketing data for Xeljanz that revealed a higher risk of malignancies, venous thromboembolism, and major adverse cardiovascular events (MACE), such as myocardial infarction, than tumor necrosis factor (TNF) inhibitors.

“It seems likely that the FDA has requested similar data on malignancies and MACE from developers for their applications still under consideration and have now requested additional months to review such data.”

For AD, delays now put all three agents, Olumiant, Rinvoq, and abrocitinib, on track for approval in Q3 2021. However, experts have suggested that perhaps the FDA is signaling a concern over the risk-benefit profile of JAK inhibitors, with a lower threshold for acceptance of safety signals in this dermatologic condition, and that plans for an advisory committee meeting may be underway. If this is the case, the future of JAK inhibitors in AD may be at risk for further delays and dermatologists’ perception of the drug class may also suffer.

Leach adds: “The latest string of news may feel like déjà vu to many who have followed this drug class over the past decade. Once again, the FDA is pushing back on JAK inhibitors due to safety concerns. Although no CRL has been issued yet in AD, it may be an early warning sign that the FDA is continuing its history with a careful eye on safety signals in JAKs.”

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