Sanofi has reported "exciting" results from a proof-of-concept trial for amlitelimab (formerly KY1005), the lead drug acquired in its $1.45 billion purchase of UK biotech Kymab earlier this year. The antibody therapy, which targets OX40 ligand, showed promising efficacy in patients with moderate to severe atopic dermatitis who had inadequate control with corticosteroids.
The Phase 2a study involved 89 patients who received either a high or low dose of amlitelimab administered via intravenous infusion once every 28 days over a 12-week period, with clinical assessment at 16 weeks. Patients in the low-dose group demonstrated an average 80% improvement in Eczema Area and Severity Index (EASI) scores at the 16-week mark, compared to 49% in the placebo group—a difference described as "nominally statistically significant."
Interestingly, the high-dose group showed a slightly lower improvement of 70%, though Sanofi noted there was no meaningful difference between the dose groups, with both demonstrating improvement within two weeks of the first dose. The lack of dose-response relationship could be attributed to the relatively small sample size or the possibility that the low dose is already at or above the optimal therapeutic level.
Secondary Endpoints Reinforce Efficacy
Secondary outcome measures provided even more compelling evidence of amlitelimab's potential. In the low-dose group, 44% of patients achieved clear or almost clear skin according to the validated Investigator's Global Assessment (vIGA) scale, compared to just 8% in the placebo group—a highly significant difference.
Additionally, 59% of patients receiving the low dose achieved a 75% or greater improvement in EASI scores (EASI-75), versus 25% in the placebo group. The more stringent EASI-90 threshold was reached by 33% of low-dose patients compared to 13% of those on placebo.
These efficacy metrics are comparable to those observed in Phase 2 trials of Dupixent (dupilumab), Sanofi and Regeneron's blockbuster IL-4 and IL-13 inhibitor that has become a standard treatment for atopic dermatitis.
Durability of Response
Perhaps most notably, amlitelimab demonstrated impressive durability of effect, with two-thirds of patients who achieved clear or almost clear skin maintaining that benefit 24 weeks after the final dose. This suggests potential for extended dosing intervals, which could offer advantages over existing therapies requiring more frequent administration.
Side effects were reported more frequently in the low-dose group (35%) compared to the high-dose group (17%), which again may reflect the study's limited size and statistical power rather than a true safety signal.
Strategic Expansion in Atopic Dermatitis
The acquisition of Kymab and its lead asset represents a strategic move by Sanofi to strengthen its position in the atopic dermatitis market, where it already holds a dominant position with Dupixent. Kymab's technology platform uses transgenic mice to develop antibodies optimized for the human immune system, similar to the approach used by Sanofi's partner Regeneron.
Amlitelimab's novel mechanism of action—targeting OX40 ligand, an immune system regulator—could complement Dupixent by offering an alternative pathway for patients who don't respond adequately to existing therapies. The company is also developing a subcutaneous formulation that could improve convenience for patients.
Increasing Competition in Atopic Dermatitis
The positive results come at a time of intensifying competition in the atopic dermatitis treatment landscape. Recent market entrants include Leo Pharma's IL-13 inhibitor Adtralza (tralokinumab) and several JAK inhibitors: Lilly's Olumiant (baricitinib), AbbVie's Rinvoq (upadacitinib), and Pfizer's Cibinqo (abrocitinib)—all recently approved in Europe.
In the US, where JAK inhibitors have faced regulatory scrutiny over safety concerns, Incyte's topical therapy Opzelura (ruxolitinib) recently became the first in its class to receive FDA approval for atopic dermatitis.
Despite this crowded marketplace, Sanofi maintains that atopic dermatitis remains challenging to manage, with patients showing variable responses to available treatments. This heterogeneity underscores the need for multiple therapeutic options targeting different pathways.
Future Development Plans
Based on these encouraging results, Sanofi is planning to advance amlitelimab to a Phase 2b trial. The company appears confident that targeting the OX40 ligand pathway represents a valid strategy for addressing inflammatory skin conditions.
Beyond atopic dermatitis, Kymab's pipeline includes KY1044, an ICOS agonist monoclonal antibody currently in early Phase 1/2 development as both monotherapy and in combination with an anti-PD-L1 for oncology indications.
The Kymab acquisition aligns with Sanofi's broader strategic pivot toward innovative therapies for cancer and inflammatory diseases, moving away from its traditional focus on diabetes treatments as its insulin product Lantus has faced generic competition. This follows Sanofi's $3.4 billion acquisition of Principia Biopharma in August 2020, which added several BTK inhibitor candidates for autoimmune disorders to its pipeline.
