Amlitelimab, Sanofi’s anti-OX40L antibody, met all primary and key secondary endpoints in a Phase 3 study of patients aged 12 years and older with moderate-to-severe atopic dermatitis (AD).
The investigational anti-OX40L antibody demonstrated statistically significant and clinically meaningful skin clearance and disease severity compared to placebo at Week 24, with efficacy progressively increasing throughout the treatment period. Amlitelimab was also well-tolerated, with no new safety concerns identified in this study.
The COAST 1 study was a randomized, double-blind, placebo-controlled, parallel-group, three-arm, global, multicenter Phase 3 study to evaluate the efficacy and safety of amlitelimab monotherapy by subcutaneous injection in 601 adults and adolescents aged 12 years and older with moderate-to-severe AD.
Objectives and Endpoints
Key objectives included measuring the efficacy and safety of amlitelimab compared to placebo at Week 24. In the study, amlitelimab was administered at a dose of 250mg (125mg for those with body weight <40kg) on either an every-four-weeks (Q4W) or every-12-weeks (Q12W) schedule following a loading dose of 500mg (250mg for those with body weight <40 kg). The study included sites in 15 countries across North America, Latin America, Europe, Asia-Pacific, and the Middle East, reflecting a diverse study population.
The key endpoints were measured at Week 24 in patients who received amlitelimab either Q4W or Q12W. For the U.S. and U.S. reference countries, the primary endpoint was the proportion of patients with a validated Investigator’s Global Assessment (IGA) scale for AD (vIGA-AD) of 0 (clear) or 1 (almost clear) and a reduction from baseline score of ≥2 points.
For the EU, EU reference countries, and Japan, the co-primary endpoints comprised the proportion of patients with vIGA-AD 0/1 and a reduction from baseline score of ≥2 points, along with the proportion of patients reaching a 75% or greater improvement in the Eczema Area and Severity Index total score (EASI-75).
Key endpoints Proportion of patients | Non-responder imputation* | Treatment policy** | ||||
| Q4W | Q12W | Placebo | Q4W | Q12W | Placebo | |
| vIGA-AD 0/1 | 21.1% p-value (p)<0.01 | 22.5% p <0.01 | 9.2% | 26.5% p <0.001 | 29.1% p <0.001 | 10.5% |
| EASI-75 | 35.9% p <0.001 | 39.1% p <0.001 | 19.1% | 46.0% p <0.001 | 50.3% p <0.001 | 27.6% |
* Non-responder imputation: includes patients with rescue/prohibited medication use before Week 24 and missing data.
** Treatment policy: includes data for patients with rescue medication use before Week 24. Note: In both analyses, non-responder imputation for patients with prohibited medication use and missing data.
In both treatment arms, a progressive increase in efficacy without plateau was observed during the treatment period:
(Treatment effects at Week 24 are modeled and do not reconcile with the table.)
Data Falls Short of Analyst Expectations
The data fell short of TD Cowen analysts’ expectations, according to media reports. Based on Phase 2 results, TD Cowen analysts said that their base case Phase 3 readout was a 45% to 50% rate of EASI-75 and a 35% to 40% rate of IGA0/1 after 24 weeks of monthly dosing.
The study’s key secondary endpoints were also achieved across both dosing arms at Week 24, including the proportion of patients who achieved a vIGA-AD 0/1 with only barely perceptible erythema and a reduction from baseline of ≥2 points, and the proportion of patients who achieved a ≥4-point reduction in Peak Pruritus-Numerical Rating Scale (PP-NRS) from baseline in patients with a baseline PP-NRS ≥4.
The most common Treatment-Emergent Adverse Events (TEAEs) in COAST 1 (≥5% in any dose arm) were AD, nasopharyngitis, and upper respiratory tract infection. All were more common in the placebo arm compared to the amlitelimab-treated arms. Injection-site reactions were numerically higher in the amlitelimab arms (pooled amlitelimab 2.2%, placebo 0.7%). All were mild, patients recovered, and study medication was continued in all cases.
Rates of pyrexia (1.1% in pooled amlitelimab arms vs. 0.7% in placebo arm) and chills (0.4% in pooled amlitelimab arms vs. 0% in placebo arm) were low. Overall, rates of TEAEs, serious adverse events, and TEAEs resulting in treatment discontinuation were similar in the placebo arm and the pooled amlitelimab arms.
A Significant Treatment Advance
“These positive first Phase 3 results of amlitelimab reinforce the potential of targeting the OX40-ligand to normalize the overactive immune system, without depleting T cells,” says Houman Ashrafian, Executive Vice President, Head of Research & Development at Sanofi, in a news release. “Amlitelimab may represent a significant advance in the treatment of atopic dermatitis with clinically meaningful and progressively increasing efficacy, with the potential of dosing only four times per year. These promising data, seen in a study population that more closely resembles today’s diverse patient landscape, including a substantial proportion previously treated with advanced therapies, support our ambition to deliver a differentiated medicine. We look forward to sharing additional Phase 3 results from the OCEANA clinical development program.”
Amlitelimab is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.
Full results will be submitted for presentation at a forthcoming medical meeting.
The OCEANA clinical development program of amlitelimab in AD, which includes COAST 1 and four other Phase 3 studies (SHORE, COAST 2, AQUA, and ESTUARY), is anticipated to read out through 2026 and comprises the foundation for potential global regulatory submissions.
