Eli Lilly and Company announced that it was discontinuing the Phase III development program for Olumiant (baricitinib) in lupus.
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Eli Lilly and Company announced that it was discontinuing the Phase III development program for Olumiant (baricitinib) in lupus. This was based on data from two pivotal Phase III clinical trials, SLE-BRAVE-I and II.
Olumiant is a once-daily, oral JAK inhibitor discovered by Incyte and licensed to Lilly. It is approved for adults with moderate to severe rheumatoid arthritis and for moderate to severe atopic dermatitis patients who are candidates for systemic therapy. In addition, it has an Emergency Use Authorization (EUA) in the U.S. for COVID-19 in hospitalized adults and pediatric patients two years or older who require supplemental oxygen, non-invasive or invasive mechanical ventilation or ECMO.
The two lupus studies had differing results. The SLE-BRAVE-I study evaluated 4 mg of the drug and demonstrated a statistically significant decrease in disease activity as measured by percentage of adults with active lupus who achieved an SRI-4 response at Week 52 compared to placebo. SRI-4 is a composite measure of overall disease activity. The SLE-BRAVE-II study, however, did not hit the primary endpoint of SRI-4 response. Key secondary endpoints of both studies were not met either.
Lilly is also working with researchers to appropriately end the Phase III SLE long-term extension study, SLE-BRAVE-X, which was supposed to evaluate long-term safety and efficacy of Olumiant over three years in people who completed the SLE-BRAVE-I and II studies.
Also, the company is discussing with the U.S. Food and Drug Administration the status of a supplemental New Drug Application (sNDA) for Olumiant for adults with moderate-to-severe atopic dermatitis. Lilly reports that currently they are not in alignment with the FDA on the indicated population and think there is a chance the FDA will reject the sNDA.
The efficacy and safety of Olumiant were studied in eight atopic dermatitis trials, including in patients where the disease is not appropriately controlled with topical prescription drugs or when those drugs aren’t advisable.
“On behalf of all of us at Lilly, we thank the participants, trial sites and clinical investigators for their essential contributions to the Olumiant atopic dermatitis and lupus programs,” said Dr. Lotus Mallbris, vice president of global immunology development and medical affairs at Lilly. “We are disappointed for the millions of people who suffer from these complex and hard-to-treat autoimmune diseases and are in need of more treatment options, and we remain committed to pursuing treatment advances in immunology that can make life better for people around the world. Those decisions do not affect Lilly’s other research efforts for Olumiant or its approved indications. We are confident in Olumiant for approved indications in the U.S. and globally as Olumiant has one of the largest and longest sets of available data in the JAK inhibitor class, including nine years across the clinical development program.”
Lilly and Incyte inked the original global license and collaboration deal for Olumiant in late 2009.
Although not spelled out by Lilly, a likely explanation for the impasse with the FDA over the atopic dermatitis sNDA is the FDA’s concerns over JAK inhibitor safety. An updated warning by the regulator in September required warnings about increased risk of heart-related events such as heart attack or stroke, cancer, blood clots and death with JAK inhibitors, specifically citing Pfizer’s Xeljanz and Xeljanz XR (tofacitinib).
The FDA stated at the time, “We are requiring new and updated warnings for two other arthritis medicines in the same drug class as Xeljanz, called Janus kinase (JAK) inhibitors, Olumiant (baricitinib) and Rinvoq (upadacitinib). Olumiant and Rinvoq have not been studied in trials similar to the large safety clinical trial with Xeljanz, so the risks have not been adequately evaluated. However, since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.”
Lilly, in its announcement, said that Olumiant had not demonstrated any new safety issues in eight trials for atopic dermatitis.
