Breakthrough Clinical Results
Sanofi announced positive topline results from the COAST 1 Phase 3 clinical trial of amlitelimab, a monoclonal antibody targeting OX40L, in adults and adolescents with moderate-to-severe atopic dermatitis (AD). Amlitelimab, administered every four weeks or every twelve weeks, met all primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvements in skin clearance and disease severity compared to placebo at Week 24. The drug was well-tolerated, with no new safety concerns. These results support the potential of amlitelimab as a first-in-class treatment for AD, offering the possibility of dosing only four times per year. Further Phase 3 data are expected through 2026.
Key Highlights
- Amlitelimab met all primary and key secondary endpoints in the COAST 1 Phase 3 study.
- Statistically significant and clinically meaningful improvements in skin clearance and disease severity were observed compared to placebo.
- Amlitelimab was well-tolerated with no new safety concerns identified.
- Potential for dosing only four times per year.
Incidence and Prevalence
Global Prevalence and Incidence of Atopic Dermatitis
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease characterized by barrier defects, immune dysregulation, and increased skin infections. Recent epidemiological data reveals significant global patterns in its distribution and prevalence.
Global Burden
In 2021, there were an estimated 129 million (124-134) individuals with atopic dermatitis worldwide. This represents a consistent increase from 107 million (103-112) cases in 1990. According to forecasting models, 148 million (140-158) atopic dermatitis cases are expected by 2050.
The worldwide prevalence of atopic dermatitis is estimated at 171 million people. AD affects approximately 20% of children globally according to a 2022 study.
Regional Variations
In Western industrialized nations, the prevalence ranges from 2.5% to 3.5% in adults and 10% to 15% among children. The point-prevalences of eczema in African countries studied were comparatively low: 1.5% and 1.6% in Ghana; 4% in Gabon; and 0.8% in Rwanda.
Regional studies show varying prevalence rates: - In Puerto Rico, prevalence among schoolchildren aged six and seven was 24.8% - In Greenland, lifetime prevalence among younger schoolchildren was 14.0% - In northern China, eczema prevalence was 15.7%, while the prevalence of eczema with asthma and/or hay fever was 5.1%
Trends and Patterns
The age-standardised prevalence rates for atopic dermatitis decreased by 8.3% (from 1885.4 per 100,000 to 1728.5 per 100,000) from 1990 to 2021. However, these rates are expected to remain relatively stable (-1.4% [-9.1 to 7.0]) from 2021 to 2050.
The estimated lifetime prevalence of atopic dermatitis has increased 2-3 fold during the past 30 years, especially in urban areas in industrialized countries. The prevalence is increasing in Africa, eastern Asia, western Europe and parts of northern Europe.
Risk Factors
Several factors influence AD prevalence: - Socioeconomic status: In Puerto Rico, higher prevalence was observed in private schools (31.0%) compared to public schools (19.9%) - Environmental factors: A Singapore study found associations between AD consultations and ambient particulate matter concentrations and rainfall - Demographic factors: In China, prevalence was associated with younger age, atopy family history, high education level, urbanization, and antibiotic overuse - Urban vs. rural: There is evidence of higher risk for eczema in urban compared with rural areas
The highest age-standardised DALY rate for atopic dermatitis was found in the high-income super-region (3552.5 [3407.2-3706.1] per 100,000) in 2021, indicating a significant disease burden in more developed regions.
Emerging End Points
Emerging Key Endpoints for Atopic Dermatitis
Biomarkers
Recent research has identified several emerging biomarkers for atopic dermatitis (AD). While CCL17/TARC is considered the most reliable biomarker, newer studies show that squamous cell carcinoma antigen 2 (SCCA2), CCL26/eotaxin-3, and lactose dehydrogenase (LDH) may be superior for assessing clinical severity and disease activity. The VEGF/VEGFR system has been implicated in AD pathogenesis, while SC pH and SC ceramides show potential as biomarkers for disease progression and therapeutic targets.
Clinical Efficacy Endpoints
Primary efficacy endpoints in recent clinical trials include Investigator's Global Assessment (IGA) of clear/almost clear skin (IGA 0/1) and Eczema Area and Severity Index (EASI) scores, particularly EASI-75 (75% improvement). Secondary measures include EASI-50, EASI-90, Worst Pruritus Numeric Rating Scale, and various patient-reported outcomes.
Patient-Reported Outcomes
Patient-centered endpoints have gained prominence, including the Dermatology Life Quality Index (DLQI), Patient Oriented Eczema Measure (POEM), Short Form 36 Health Survey (SF-36), AD control tool, and sleep quality numerical rating scale. Recent studies show increasingly greater improvements in PROs at higher clinical response levels, with mean percentage improvement exceeding 69% at EASI ≥ 90 for most PROs.
Skin Barrier Function
Skin barrier dysfunction is now recognized as a critical endpoint, with research focusing on elevated SC pH, alterations in SC ceramide profiles, and filaggrin restoration. These factors contribute to increased permeability, immune dysregulation, and microbial imbalances in AD patients.
Infection Control
Infection control has emerged as an important endpoint, as AD patients have significantly higher odds of bacterial, viral, fungal, and sexually transmitted skin infections. Specific infections include carbuncle/furuncles, impetigo, MRSA, molluscum contagiosum, herpes simplex, and candidiasis, with skin infections associated with US $19 million excess annual costs in ED care.
Healthcare Resource Utilization
Healthcare resource utilization (HRU) is increasingly tracked as an endpoint, with recent advances in biologics-based AD management potentially reducing healthcare touchpoints. Studies show moderate-to-severe AD patients had 6.6 dermatology clinic visits per patient-year and 1.6 flares requiring additional medical advice per patient-year.
Emerging Therapeutic Approaches
Novel endpoints related to therapeutic approaches include non-invasive pH assessment for personalized interventions, advances in lipid analyses for next-generation therapies, and novel compounds like Ac-RLYE (a tetrapeptide) showing promise in relieving AD-like symptoms.
Treatment Reporting Standards
Improved standardized approaches to reporting topical therapy in AD trials are emerging as important endpoints to enhance transparency and interpretability, particularly regarding concomitant topical treatments, rescue topicals, and criteria for using rescue topical treatments.
Drug used in other indications
Amlitelimab Clinical Trials Beyond Atopic Dermatitis
Based on the available information, Amlitelimab (an anti-OX40L monoclonal antibody) has not been documented as being tested in clinical trials for any indications other than atopic dermatitis (AD).
The only documented clinical application of Amlitelimab is for the treatment of moderate-to-severe atopic dermatitis, where it has shown promise alongside Rocatinlimab (which targets OX40 rather than OX40L).
Since there are no trials identified for indications beyond atopic dermatitis, there are no intervention models, dosing regimens, or administration protocols to report for other conditions.
The current clinical development of Amlitelimab appears to be focused exclusively on exploring its efficacy in atopic dermatitis management, leveraging its mechanism of targeting the OX40L pathway in immune regulation.
For patients and clinicians interested in Amlitelimab for conditions other than atopic dermatitis, no clinical trial data is currently available to support its use in alternative indications.