Sanofi has reported Phase III data from its eczema candidate amlitelimab, showing that the therapy met primary and key secondary endpoints but delivered efficacy results that fell below analyst projections. The announcement led to a decline in Sanofi’s stock, with shares opening down 9% in Paris.
The late-stage COAST-1 study tested amlitelimab, an anti-OX40L antibody that Sanofi has projected could generate peak sales exceeding $5 billion. More than 600 patients aged 12 years and older with moderate-to-severe atopic dermatitis participated in the trial. Sanofi disclosed that amlitelimab achieved the co-primary endpoints of the study, but analysts noted the outcomes were weaker than expected.
Results showed that after 24 weeks of monthly subcutaneous dosing, amlitelimab achieved an EASI-75 rate of 35.9%, while dosing every 12 weeks delivered an EASI-75 rate of 39.1%. Placebo patients recorded 19.1%. Sanofi also reported validated investigator global assessment scale for atopic dermatitis (vIGA-AD) 0/1 rates of 21.1% and 26.5%, depending on patient inclusion criteria.
EASI-75 measures the proportion of patients experiencing at least a 75% improvement in the eczema area and severity index, while vIGA-AD assesses the proportion with clear or almost clear skin. By comparison, TD Cowen analysts had anticipated a higher efficacy range, estimating 45% to 50% EASI-75 and 35% to 40% IGA0/1 rates in their base case scenario.
Market reaction followed quickly. Sanofi’s shares dropped to 78.36 euros in early Paris trading, while Nasdaq trading saw the company down more than 7% on Wednesday morning.
Analyst commentary focused on the difference between expectations and outcomes. Jefferies wrote that amlitelimab “doesn’t replicate [phase 2] efficacy and looks soft compared to other biologics. However, the drug clearly works at dosing every 12 weeks with efficacy improving over time, and is safe.”
Leerink analysts said the therapy could still find use in second-line settings given its novel mechanism and Q12W dosing schedule. William Blair analysts said that the magnitude of benefit with amlitelimab came well below investor expectations when compared to approved benchmarks, including Dupixent.
Dupixent, the treatment developed by Sanofi and Regeneron, has previously demonstrated stronger results, with EASI-75 rates between 44% and 69% after 16 weeks in Phase III studies. Leerink Partners noted that amlitelimab’s outcomes were “meaningfully inferior” to Dupixent, which they described as the bar for compelling results.
Analysts also compared amlitelimab with Amgen’s OX40-targeting antibody rocatinlimab, which showed Phase III data but also fell short of Dupixent’s efficacy. Both agents, according to analysts, may be positioned as second-line biologics for patients not responding to IL-13/4 therapies.
Sanofi is continuing the development of amlitelimab through its OCEANA program, which includes SHORE, COAST-2, AQUA, and ESTUARY. Data from these studies are expected through 2026 and may form the basis for global regulatory submissions.
TD Cowen described these upcoming readouts as “mission critical” for Sanofi, emphasizing amlitelimab’s importance not only for peak sales potential but also for sentiment around the company’s research and development efforts.
From a strategic perspective, Sanofi must also manage the looming patent expiry of Dupixent (2021-2031 window), making successful execution of the immunology pipeline essential. Amlitelimab’s trajectory will likely influence investor confidence, R&D pace, and internal prioritization of other pipeline assets.
In conclusion, Sanofi’s amlitelimab has cleared key regulatory hurdles in COAST-1 by meeting endpoints, but the luke-warm reception from markets and analysts reflects skepticism about its ability to displace existing standards. The next wave of trial data will be critical in clarifying whether amlitelimab can justify its high expectations and occupy a meaningful place in treatment guidelines. While the COAST-1 results represent a clinical achievement for Sanofi, the underwhelming efficacy relative to expectations exposes challenges the company must contend with going forward.
