Kymab Ltd.

Shares in Sanofi fell more than 9% on Thursday after the first Phase III results for its key pipeline hopeful amlitelimab in moderate-to-severe atopic dermatitis (AD) came up short of expectations. The findings from the COAST 1 study deal a blow to the French drugmaker's efforts to find a successor to its current top-seller Dupixent (dupilumab). In the trial, both doses of the anti-OX40L antibody amlitelimab — given every four weeks or every 12 weeks — met all primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful skin clearance and disease severity compared to placebo at week 24 in patients aged 12 years and older with moderate-to-severe AD. However, the improvements were less than those seen with Dupixent and also below those from earlier studies of amlitelimab. For related analysis, see Spotlight On: AAD25 – Sanofi looks like one to beat in OX40 faceoff with Amgen. Sanofi noted that in COAST 1, amlitelimab given every four weeks was associated with a validated Investigator's Global Assessment (vIGA) score of 0 or 1 in 26.5% of patients, rising to 29.1% in the every-12-weeks group, versus 10.5% for placebo. Meanwhile, the percentage of patients achieving a ≥75% improvement in Eczema Area and Severity Index score (EASI 75) in the two amlitelimab arms were 46% and 50.3%, respectively, compared to 27.6% for placebo. Analysts at JPMorgan said the data confirmed that amlitelimab is less effective than Dupixent, while Jefferies suggested that despite the Phase III results falling short of earlier findings and of rival biologic drugs, the drug's safety profile and convenient 12-week dosing could still support its use.  Barclays analyst Emily Field noted that ahead of the readout, investors had viewed amlitelimab as Sanofi's lead pipeline asset. "That's why we're seeing a big reaction in the stock, because of the concern that Sanofi is not going to have enough in its pipeline to replace Dupixent after patent expiry," which is set for 2031. The French drugmaker gained amlitelimab via the $1.1-billion purchase of Kymab in 2021.

iStock, wildpixel Analysts at Leerink agreed with Sanofi that, despite falling short of statistical significance in the Phase II TIDE-Asthma trial, amlitelimab warrants further development in this indication. Sanofi ’s amlitelimab, the centerpiece of the pharma’s $1.4 billion acquisition of Kymab, failed to significantly reduce disease exacerbations in patients with moderate-to-severe asthma in a mid-stage trial. Nevertheless, Sanofi insisted that amlitelimab’s treatment benefits were “clinically meaningful” and that the results support further study of the asset in asthma. Analysts at Leerink Partners agreed, telling investors in a Tuesday note that “these findings support continued development despite the missed 48-[week] primary endpoint.” The preliminary readout released Tuesday comes from the Phase II TIDE-Asthma trial. In particular, Leerink pointed to Sanofi’s data in the subgroup of patients with at least 300 eosinophils/mL and elevated levels of neutrophils. According to Tuesday’s release, amlitelimab was able to reduce asthma exacerbations by more than 70% in this population at week 60, alongside improvements in lung function. This matches or exceeds the performance of Sanofi and Regeneron’s prized drug Dupixent and Amgen and AstraZenca’s Tezspire—two products that are dominant in the asthma market. The drugs have “demonstrated a risk reduction in annualized exacerbation rates [versus placebo] of 66-70% in these patient subgroups,” the Leerink group wrote. Sanofi also revealed on Tuesday that amlitelimab was able to elicit only “nominally significant” improvements in secondary endpoints, including lung function and asthma control. Still, the pharma called the drug’s efficacy profile “compelling,” saying that amlitelimab “has the potential to improve key disease outcomes” in asthma. The pharma is currently in the process of planning a Phase III trial for amlitelimab in this indication, as per the Tuesday announcement. Amlitelimab, an investigational monoclonal antibody, works by targeting OX40L, a central player in the regulation of the immune response. This mechanism of action holds potential to rebalance the immune system, according to Sanofi, in turn addressing several immune-mediated and inflammatory conditions. Leerink pointed out that Sanofi has named amlitelimab “as one of its top three pipeline assets, with peak sales potential exceeding €5 billion.” The bulk of this opportunity, according to the analysts, comes from the atopic dermatitis market. Phase IIb data in June 2023 showed that amlitelimab significantly reduced eczema severity in patients with moderate-to-severe disease. Additional data are expected in 2026, Leerink noted. Aside from asthma and atopic dermatitis, Sanofi is also trialing amlitelimab in hidradenitis suppurativa , alopecia areata , celiac disease and scleroderma .

Sanofi’s efforts to explore its OX40-ligand targeting drug for inflammatory diseases other than eczema have hit a roadblock as the drug failed a Phase 2 trial in patients with asthma. The French drugmaker obtained the candidate, dubbed amlitelimab, as part of its $1.45 billion buyout of Kymab in 2021. The highest dose of amlitelimab missed the Phase 2 trial’s primary endpoint of an annualized rate of severe flare-ups at 48 weeks, according to preliminary results shared Tuesday. The medium and low doses of the drug seemed to perform better on the same measure, but because the highest dose missed the mark, those data had only “nominal significance.” The placebo-controlled Phase 2 TIDE-Asthma trial tested amlitelimab as an add-on to standard of care in 448 people with moderate to severe asthma. Results from the study were initially expected towards the end of last year but were pushed back in October to the first half of 2025. The delay raised the suspicions of Leerink analysts, who wrote they were “cautious” about the readout last month. Sanofi maintained that some parts of the Phase 2 data suggest there’s still a path forward in asthma. The medium dose of amlitelimab produced “nominally significant and clinically meaningful reductions” in severe flare-ups at 60 weeks in a subgroup of patients with heterogeneous inflammatory disease, the company said. If these results are replicated in later studies, they could represent a “breakthrough” for this population, Sanofi claimed. Sanofi is planning a Phase 3 program for amlitelimab in asthma. But the product’s most advanced indication is atopic dermatitis, which is being evaluated in the Phase 3 OCEANA program. Last month, Sanofi shared updated Phase 2 data showing the drug improved eczema symptoms through 28 weeks. The OX40-ligand drug is designed for quarterly dosing after an initial loading dose, giving it a potential convenience advantage over more frequently administered eczema treatments, including Sanofi’s own Dupixent. Sanofi also noted on Tuesday that it has kicked off two Phase 3 and one Phase 2 trial of its Regeneron-partnered IL‐33 targeting drug, itepekimab, in chronic rhinosinusitis. Itepekimab is also in a pair of Phase 3 studies in chronic obstructive pulmonary disease, with readouts expected in the second half of this year. The company also expects to start a Phase 2/3 COPD trial of its dual IL-13/TSLP inhibitor, lunsekimig, this year.