In a phase 2 atopic dermatitis trial, Eli Lilly and Incyte's baricitinib hit its primary endpoint but missed a secondary objective, prompting unfavorable comparisons with Sanofi and Regeneron's recently approved Dupixent.
The oral JAK inhibitor was compared to placebo alongside topical steroid treatment in patients with moderate to severe atopic dermatitis (also known as eczema) in the trial. At the highest dose tested (4 mg), 61% of patients on baricitinib had at least a 50% reduction in symptoms (EASI-50), compared to 37% of the steroid plus placebo group, said Lilly.
From there, the data becomes less impressive. The lower 2 mg dose arm failed to show a significant difference from the control group, and on another secondary endpoint—a 75% improvement in symptoms or EASI-75—neither dose outperformed control. Analysts at Jefferies said that the data don't match the results seen in phase 2a with Dupixent (dupilumab) injections plus steroids, and suggest much of the effect with baricitinib is seen in more severely affected patients.
Lilly is sufficiently encouraged by the results to press on with a phase 3 program for baricitinib in atopic dermatitis later this year.
Bagging an atopic dermatitis for baricitinib could help Lilly and Incyte restore momentum to the drug, which was knocked back earlier this year after the FDA turned down a marketing application in rheumatoid arthritis, its lead indication.
Baricitinib is on sale in Europe as Olumiant, and Lilly and Incyte said recently that it would be able to refile its U.S. application early next year, much sooner than anticipated and potentially shortening the delay before baricitinib can compete with Pfizer's JAK inhibitor Xeljanz (tofacitinib) in rheumatoid arthritis.
Xeljanz is heading for blockbuster sales this year, having racked up $587 million in the first half, but isn’t in development for atopic dermatitis. However, Lilly and Incyte's could have a potent rival in atopic dermatitis with AbbVie's rival JAK inhibitor upadacitinib, which is also en route to phase 3 testing this year.
Jefferies noted that upadacitinib announced a significant improvement on the EASI-75 measure in its recent trial announcement and appeared comparable to Dupixent, but stressed AbbVie hasn't yet revealed baseline characteristics from the trial to allow a like-for-like comparison.
Nevertheless, they said that "dupilumab edges out baricitinib on key endpoints," and in comparison, Lilly and Incyte's data "appear lackluster".
Lilly's global brand development leader for biomedicines, James McGill, M.D., thinks there is a pressing need for new therapeutic options in atopic dermatitis.
"Atopic dermatitis has a significant impact on the quality of life, including the emotional and social wellbeing of people with the disease," he said. "The study was designed to understand the safety and efficacy of baricitinib in patients refractory to topical steroids [and] in this population, baricitinib was able to achieve improvement in both itch and skin inflammation."