Sanofi’s blockbuster ambitions for amlitelimab hit a bump in the road this morning with the news that the highest dose of the anti-OX40-ligand monoclonal antibody missed the main goal of a phase 2 asthma study.
The French pharma has been evaluating three doses of the drugs an add-on therapy in the Tide-Asthma trial of 437 patients with moderate to severe asthma. The primary endpoint of the study was the annualized rate of severe asthma exacerbations at Week 48.
As part of a broader update of Sanofi’s respiratory portfolio, the company revealed that the highest dose of amlitelimab had missed this key endpoint. The Big Pharma mined the results for positive signals, arguing that the medium dose “led to nominally significant and clinically meaningful reductions” in exacerbations compared with placebo, while a “numerically greater reduction in exacerbations” had been seen in the high-dose cohort by Week 60.
Drilling down into subgroups of patients, Sanofi also claimed that amlitelimab demonstrated “compelling efficacy” in patients with heterogeneous inflammatory asthma. This would “potentially represent a breakthrough for this underserved patient population if observed in later studies,” the company said.
Sanofi didn’t divulge much hard data, but it did say that among a subgroup of patients defined by eosinophil and neutrophil biomarkers, amlitelimab showed a “nominally significant and clinically meaningful” reduction in exacerbations of more than 70% at Week 60.
Seemingly undeterred by the headline failure, Sanofi said it would push ahead with plans for a phase 3 asthma trial for amlitelimab.
“In asthma, amlitelimab shows potential as an effective, long-acting medicine, including in patients with moderate-to-severe heterogenous inflammation,” Sanofi’s head of R&D Houman Ashrafian, Ph.D., said in the April 15 release.
“If the preliminary effect we have seen is confirmed in phase 3 studies, amlitelimab could become a differentiated treatment option in asthma,” Ashrafian added. “These data validate our strategy to advance innovative science and provide new solutions for patients with challenging-to-treat respiratory diseases.”
Even if amlitelimab falls short in asthma, Sanofi is also evaluating the drug across a range of immune-mediated diseases and inflammatory disorders. The company is running a phase 3 study of the candidate in atopic dermatitis and phase 2 trials in hidradenitis suppurativa, systemic sclerosis, celiac disease and alopecia.
The strategy echoes Sanofi’s approach to Dupixent, development of which expanded quickly beyond its initial focus on eczema and asthma.
Sanofi secured amlitelimab as part of its $1.1 billion acquisition of Kymab back in 2021. By 2023, the drug had proven its worth in a phase 2 atopic dermatitis trial, leading the pharma to list the anti-OX40 antibody alongside the multiple sclerosis drug frexalimab and the psoriasis pill SAR441566 as candidates with potential peak sales of more than 5 billion euros.
Sanofi sees targeting OX40-ligand as a way to restore immune homeostasis between pro-inflammatory and regulatory T cells. Hitting OX40-ligand rather than OX40 should, in theory, increase the antibody’s effect on T-cell stimulation while maintaining regulatory T cells, according to the company.
On a full-year earnings call in January, Ashrafian told analysts that 2025 was an “exciting time for amlitelimab, as we continue the quickening drumbeat, particularly in disorders like asthma and hidradenitis suppurativa.”