Sanofi’s development of an oral spin on Humira’s mechanism has hit a setback. The candidate fell short in a phase 2 psoriasis trial, prompting the French drugmaker to pull back from plans to develop the molecule as a monotherapy.
Led by AbbVie’s Humira, biologic TNF inhibitors transformed the treatment of autoimmune diseases over the past 20 years. However, the biologic modality can cause adverse effects and loss of efficacy in some patients. Sanofi identified the small molecule balinatunfib as a candidate that could bypass those issues and, by inhibiting TNFR1 but not TNFR2, offer a differentiated side effect profile compared to biologics.
The Big Pharma put the idea to the test in a phase 2 trial that enrolled 221 people with psoriasis to take balinatunfib as a monotherapy. After 12 weeks, Sanofi found its small molecule was statistically no better than placebo on a measure of the proportion of patients whose symptoms improved by at least 75%, the French company revealed in its first-quarter 2025 earnings results.
Sanofi blamed the primary endpoint miss on “the nature of this limited phase 2 study.” Efficacy levels were “comparable to other oral medicines in psoriasis,” according to the company, and the data support the potential for differentiated safety. Based on the results, Sanofi believes balinatunfib could pair well with other drugs and is looking into opportunities including fixed-dose combinations in various diseases.
On an earnings call in January, Houman Ashrafian, Ph.D., head of R&D at Sanofi, said the company would look to establish balinatunfib as pre-biologic monotherapy if phase 2 data supported single-agent use. While the phase 2 efficacy data have closed that avenue off, Sanofi continues to believe in the combination opportunities that Ashrafian sketched out in January.
“There's a logic for it to be used in combination treatment strategies, particularly in the modern era where we have seen the combination cytokine blockade can both increase the efficacy ceiling or surpass efficacy ceiling and also provide durability,” the Sanofi executive said on the same January call. Sanofi CEO Paul Hudson added at the time that “if safety is right, the combination opportunity is significant.”
Sanofi expects to publish phase 2 data on balinatunfib in rheumatoid arthritis in the second half of 2025. The readout could confirm the small molecule has a profile that is suitable for further development in combinations. Sanofi noted in this morning's earnings presentation that rheumatoid arthritis is “already a combination market.” Sanofi recently began phase 2 trials in Crohn’s disease and ulcerative colitis.
The company disclosed the balinatunfib update alongside news about a phase 2 trial of brivekimig. The study, which tested the TNFxOX4OL nanobody in hidradenitis suppurativa, met a primary endpoint that looked at the effect on total abscess and inflammatory nodule count. Sanofi is prioritizing brivekimig in the indication because it looks more efficacious than the anti-OX40L antibody amlitelimab.