FDA Delays Review of Lilly’s Olumiant sNDA for Moderate-to-Severe Atopic Dermatitis

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On April 6, Eli Lilly and its partner Incyte announced that the U.S. FDA had extended the review period for a supplemental new drug application (sNDA) for the oral anti-inflammatory drug Olumiant (baricitinib). The sNDA seeks FDA approval for a new indication of Olumiant: the treatment of adult patients with moderate-to-severe atopic dermatitis (AD).

The FDA has postponed the target action date to allow time for review of additional data analyses submitted by Eli Lilly in response to the agency’s recent information request. The Prescription Drug User Fee Act (PDUFA) action date for the aforementioned sNDA has been extended by three months, to early Q3 2021.

The active pharmaceutical ingredient of Olumiant is baricitinib, an oral, selective, and reversible JAK1 and JAK2 inhibitor discovered by Incyte and licensed to Eli Lilly for development. It is indicated for the treatment of various inflammatory and autoimmune diseases, including rheumatoid arthritis, psoriasis, atopic dermatitis, alopecia areata, systemic lupus erythematosus, and juvenile idiopathic arthritis.

To date, Olumiant has been approved in the United States and more than 70 countries for the treatment of adult patients with moderate to severe rheumatoid arthritis who are candidates for systemic therapy. Recently, Olumiant was also approved in the European Union and Japan for the treatment of adult patients with moderate to severe atopic dermatitis (AD). It is important to note that the U.S. labeling for Olumiant includes a Boxed Warning highlighting risks such as serious infections, malignancies, and thrombosis.

Notably, the FDA has recently extended the review periods for two supplemental New Drug Applications (sNDAs) for AbbVie’s oral JAK inhibitor, Rinvoq. Currently, Rinvoq is approved in the United States for the treatment of rheumatoid arthritis, and in the European Union for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The U.S. prescribing information for this drug also carries a boxed warning identical to that of Olumiant.

Of the two sNDAs whose reviews were deferred, one pertains to the treatment of adolescent and adult patients with moderate-to-severe atopic dermatitis (AD), and the other relates to the treatment of adult patients with active psoriatic arthritis. The reasons for deferring the review periods for these two sNDAs are the same as those for Eli Lilly’s Olumiant. This is because the FDA has safety concerns regarding the JAK inhibitor class of drugs and requires additional time to comprehensively review the supplementary information submitted by the respective companies in response to its requests.

Mizuho analyst Vamil Divan pointed out that the FDA’s request for additional data on multiple JAK inhibitors stems from essentially the same reason: the long-term safety data for Xeljanz released by Pfizer in late January. Xeljanz, also an oral JAK inhibitor, demonstrated a higher risk of cardiovascular events and cancer compared with conventional TNF inhibitors (such as Humira) in a post-marketing rheumatoid arthritis trial required by the FDA.

Prior to this, the FDA first identified issues with high-dose Xeljanz in 2019 and immediately imposed restrictions on its use. The agency is currently considering whether to take further action against Xeljanz, as final analyses have demonstrated risks associated with both doses of the drug. Divan suggests that the agency may view the issues with Xeljanz as a potential class effect applicable to all JAK inhibitors.

In addition to the aforementioned JAK inhibitors, Gilead’s Jyseleca was denied FDA approval in August 2020; however, it received regulatory approval from the European Union and Japan in September 2020 for the treatment of adult patients with moderate-to-severe rheumatoid arthritis. The FDA’s primary safety concern was spermatotoxicity.

Reference Sources:

1.Lilly and Incyte communicate review extension of supplemental New Drug Application for baricitinib for the treatment of moderate to severe atopic dermatitis

2.AbbVie's Rinvoq expansion hits a 2nd snag as FDA delays $2B atopic dermatitis ruling