Dupilumab

Sanofi’s shares dipped early Thursday after its atopic dermatitis drug fell short of Wall Street’s expectations in a late-stage trial. The drugmaker’s anti-OX40L antibody, called amlitelimab, improved “skin clearance and disease severity” versus placebo at around six months in the Phase 3 COAST 1 study, according to a Thursday release . In the trial, the drug was given either every four weeks or every three months. Just over 20% of patients in the four-week dose group and 22.5% of those in the three-month group achieved “clear” or “almost clear” skin, using an analysis that counted patients who dropped out as non-responders. Both results were statistically significant compared with placebo; in that group, 9.2% of patients achieved the same outcomes. The numbers in the COAST 1 trial failed to match the performance of Sanofi’s own blockbuster eczema drug Dupixent. Around 36% to 38% of patients given Dupixent attained “clear” or “almost clear” skin in that antibody’s registrational studies after just four months. Dupixent works by inhibiting IL-4 and IL-13, and is administered every two weeks or every four weeks. Sanofi’s share price was down around 9% on the Paris exchange Thursday morning. Thursday’s results also fell short of amlitelimab’s own mid-stage trial data, Jefferies analysts said. In a Phase 2b study, 29.1% to 45.5% of patients given amlitelimab once every four weeks achieved “clear” or “almost clear” skin at the six-month mark, depending on the dose given and whether the regimen included a loading dose. But the analysts said it would be important to know how many patients in COAST 1 were previously treated with Dupixent or another systemic therapy, because these populations are more challenging to treat. Sanofi said it plans to present more detailed results at an upcoming medical meeting. The company is awaiting readouts from several other Phase 3 studies of amlitelimab in atopic dermatitis, expected throughout 2026, before submitting regulatory filings. One silver lining of the COAST 1 data was treatment safety. The most common adverse events in the study were atopic dermatitis, nasopharyngitis and upper respiratory tract infection, and all three were more common in the placebo arm than the treatment cohorts, Sanofi said.

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.