Sanofi Discontinues Development of OX40L Inhibitor Amlitelimab in Atopic Dermatitis

Sanofi announced it has discontinued clinical development of amlitelimab in moderate to severe atopic dermatitis (AD) and will not submit the OX40-ligand monoclonal antibody for global regulatory review. The company announced the decision as part of an ongoing strategic pipeline assessment. Sanofi determined the totality of efficacy and safety evidence generated to date does not support further development of amlitelimab in AD.¹

The decision closes out a mid-to-late-stage development program in AD despite positive long-term data from the phase 3 extension study. Amlitelimab selectively blocks OX40L signaling to normalize T-cell-mediated inflammation without depleting T cells, a mechanism distinct from IL-4/IL-13 and JAK-targeted therapies already available to patients. Sanofi will wind down ongoing amlitelimab AD studies and transition care for enrolled patients in coordination with investigators and regulators.¹

“It is incredibly disappointing to see amlitelimab’s development for treatment of atopic dermatitis discontinued. This is a tremendous loss for patients with AD, given the hype and promise for a new class of therapy that could impact production of multiple cytokines and potentially deliver true disease modification with less frequent dosing,” said Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine and editor in chief of Dermatology Times, in an exclusive statement.

The ESTUARY study (NCT06407934) is a phase 3 long-term extension trial evaluating amlitelimab in patients aged 12 years and older with moderate to severe AD. The extension design allowed investigators to follow patients previously enrolled in earlier amlitelimab AD studies over an extended treatment period, assessing durability of response beyond initial trial end points.¹

According to Sanofi, ESTUARY showed long-term maintenance of clinical response without relapse among patients who continued amlitelimab treatment. The company did not report specific responder rates, timepoints, or comparator data in the July 24 announcement. Despite this durability signal, Sanofi concluded amlitelimab would not represent a meaningful improvement to the standard of care for AD, weighing the totality of the program's efficacy findings against currently available systemic therapies for the condition. Sanofi plans to present additional results from the amlitelimab AD program, including further ESTUARY data, at a future medical meeting.¹

Amlitelimab Safety Profile and Regulatory Rationale

Sanofi did not disclose secondary end point data from the ESTUARY extension study or specific adverse event rates in the announcement. The company characterized the safety profile as emerging and consistent with, or building on, data from previous amlitelimab AD trials, without naming discontinuations or adverse events of special interest. No new safety signal was described in the release.¹

Sanofi weighed the combined efficacy and safety dataset against the existing standard of care for moderate to severe AD and determined amlitelimab would not offer a meaningful clinical advantage. The company stated this assessment reflects a broader strategic review of its dermatology and immunology pipeline rather than a single failed end point. Regulatory authorities were not cited as having requested additional data or raised concerns independently of Sanofi's internal review.¹

Amlitelimab's discontinuation in AD leaves clinicians without a new non-T-cell-depleting OX40L-targeted option, while IL-4/IL-13 and JAK inhibitors remain the primary systemic choices for moderate to severe disease. Sanofi noted patients and physicians continue to need additional effective treatments given the heterogeneity of immune mechanisms driving AD, and confirmed a phase 2 amlitelimab study in celiac disease remains ongoing with a readout expected in the second half of 2026.¹

Amlitelimab was the final OX40/OX40L inhibitor in development for AD, as development of rocatinlimab (Kyowa Kirin/Amgen) was also discontinued in March 2026. The discontinuation of the investigational anti-OX40 monoclonal antibody was based on emerging safety concerns—specifically, cases of malignancy. At the time of rocatinlimab’s safety review, there was 1 new confirmed case and 1 suspected case of Kaposi sarcoma, in addition to a previously confirmed case.² Sanofi has not cited any safety concerns of amlitelimab related to malignancies.¹

The financial impact is limited: Sanofi confirmed no change to full-year 2026 guidance as a result of this decision. The company reiterated its commitment to inflammatory skin disease research despite the amlitelimab AD wind-down.¹

“This decision highlights the risks pharmaceutical companies take on when developing advanced therapies for skin diseases, and we should be grateful for the time and money spent trying to help our patients. While amlitelimab now follows rocatinlimab’s frustrating departure, the best thing dermatology can do is learn from the scientific studies on the OX40-OX40L pathway so that we can use knowledge to innovate again,” Bunick said.

For clinicians managing moderate to severe AD, the pipeline retreat narrows anticipated additions to a treatment landscape already anchored by IL-4/IL-13 antagonists, JAK inhibitors, and IL-13-selective biologics.¹

References

1. Sanofi announces decision not to submit amlitelimab in atopic dermatitis for global regulatory reviews. Sanofi. July 24, 2026. Accessed July 24, 2026. https://www.sanofi.com/assets/dotcom/pressreleases/2026/2026-07-24-05-30-00-3332696-en.pdf
2. Kyowa Kirin announces discontinuation of rocatinlimab clinical trials. News release. Kyowa Kirin. March 3, 2026. Accessed July 24, 2026. https://www.globenewswire.com/news-release/2026/03/03/3248303/0/en/Kyowa-Kirin-Announces-Discontinuation-of-Rocatinlimab-Clinical-Trials.html

Frequently Asked Questions

What is amlitelimab, and why was it discontinued in atopic dermatitis?
Amlitelimab is an OX40-ligand monoclonal antibody Sanofi was developing for moderate-to-severe AD. Sanofi discontinued the program because the combined efficacy and safety evidence did not support a meaningful improvement over existing standard-of-care therapy.

How does amlitelimab work?
Amlitelimab blocks OX40L signaling, an early step in T-cell-mediated inflammatory activation, aiming to normalize immune signaling without depleting T cells.

What happens to patients enrolled in amlitelimab AD trials?
Sanofi is working with investigators, site teams, and regulators to wind down ongoing amlitelimab AD studies and ensure appropriate transition of care for all enrolled patients.