Sanofi's Amlitelimab Hits Setback in Phase 2 Asthma Trial, But Company Remains Optimistic

Sanofi's ambitious plans for amlitelimab, its anti-OX40-ligand monoclonal antibody, have encountered a significant obstacle following disappointing results from a phase 2 asthma study. The French pharmaceutical giant, however, remains committed to the drug's development across multiple indications.

Phase 2 Asthma Trial Results

In the Tide-Asthma trial, which enrolled 437 patients with moderate to severe asthma, the highest dose of amlitelimab failed to meet the primary endpoint of reducing the annualized rate of severe asthma exacerbations at Week 48. Despite this setback, Sanofi highlighted potential benefits observed in the study:

• The medium dose showed "nominally significant and clinically meaningful reductions" in exacerbations compared to placebo.
• By Week 60, the high-dose cohort demonstrated a "numerically greater reduction in exacerbations."
• In a subgroup of patients with heterogeneous inflammatory asthma, amlitelimab showed "compelling efficacy," potentially representing a breakthrough for this underserved population.
• Among patients defined by eosinophil and neutrophil biomarkers, the drug achieved a "nominally significant and clinically meaningful" reduction in exacerbations of over 70% at Week 60.

Sanofi's Response and Future Plans

Despite the primary endpoint miss, Sanofi remains optimistic about amlitelimab's potential in asthma and other indications. Dr. Houman Ashrafian, Sanofi's head of R&D, stated, "In asthma, amlitelimab shows potential as an effective, long-acting medicine, including in patients with moderate-to-severe heterogenous inflammation."

The company plans to proceed with a phase 3 asthma trial for amlitelimab. Additionally, Sanofi is evaluating the drug across a range of immune-mediated diseases and inflammatory disorders:

• A phase 3 study in atopic dermatitis is ongoing.
• Phase 2 trials are underway in hidradenitis suppurativa, systemic sclerosis, celiac disease, and alopecia.

This multi-indication strategy mirrors Sanofi's successful approach with Dupixent, which expanded beyond its initial focus on eczema and asthma.

Amlitelimab's Background and Potential

Sanofi acquired amlitelimab through its $1.1 billion purchase of Kymab in 2021. The drug has shown promise in other indications, notably succeeding in a phase 2 atopic dermatitis trial in 2023. This success led Sanofi to project potential peak sales of over 5 billion euros for amlitelimab, alongside other candidates like frexalimab for multiple sclerosis and SAR441566 for psoriasis.

The company believes that targeting OX40-ligand, rather than OX40 itself, may offer advantages in restoring immune homeostasis between pro-inflammatory and regulatory T cells. This approach could potentially increase the antibody's effect on T-cell stimulation while maintaining regulatory T cells.

As the pharmaceutical landscape continues to evolve, Sanofi's persistence with amlitelimab underscores the complex nature of drug development and the potential for unexpected findings to shape future research directions.