Atopic Dermatitis Drug Shows Promise in Phase 3 Trial

Sanofi and Regeneron recently announced top-line results from a pair of phase 3 clinical trials for dupilumab in adults with inadequately controlled moderate-to-severe atopic dermatitis (AD).

The identical SOLO 1 and SOLO 2 studies enrolled 1379 adults with moderate-to-severe AD.

Patients were randomized to receive either 300-mg of dupilumab subcutaneously once a week, 300-mg subcutaneously every 2 weeks, a placebo for 16 weeks after an initial 600-mg dose of dupilumab subcutaneously, or a placebo.

Patients were assessed using the 5-point Investigator’s Global Assessment (IGA) scale that ranges from clear (0) to severe (4). Patients were required to have a baseline score of 3 or 4 upon entry.

Additionally, the Eczema Area and Severity Index (EASI) and other measures were also used for assessment.

The results of the study showed that both trials met their clinical endpoints. For SOLO 1 and SOLO 2, 37% and 36% of patients, respectively, in the dupilumab 300-mg weekly dose group cleared or almost cleared their skin lesions (IGA 0 or 1), compared with 10% and 8.5%, respectively, in the placebo group (p less than 0.0001).

For SOLO 1 and SOLO 2, the percent improvement in EASI from baseline was 72% and 68%, respectively, for patients who received the 300-mg weekly dose, and 72% and 67% for the 300-mg of dupilumab every 2 weeks. This was in comparison to 38% and 31%, respectively, for the placebo (p less than 0.0001) cohort.

In SOLO 1 and SOLO 2, 52.5% and 48% who received dupilumab 300-mg weekly, and 51% and 44% who received dupilumab 300-mg every 2 weeks achieved EASI-75, compared with 15% and 12% with placebo (p less than 0.0001).

This result was the key secondary endpoint in the United States studies and one of the primary endpoints in the European evaluation.

The adverse events included injection site reactions and conjunctivitis, with about 26% of patients in both studies reporting a history of allergic conjunctivitis at the start of study.

“These are the first phase 3 studies of a systemic therapy to demonstrate a significant improvement in moderate-to-severe atopic dermatitis, a chronic, debilitating inflammatory disease that impacts over 1 million Americans,” said Chief Scientific Officer and President of Regeneron, George D. Yancopoulos. “These data provide strong evidence that the IL-4 and IL-13 signaling pathway is a fundamental driver of inflammation in atopic dermatitis.”

Dupilumab is the first in a new class of immunotherapies and further research will be conducted to determine the roles of the signaling pathway.

“In these 16 week trials, dupilumab blocked the aberrant activation of this pathway, resulting in significant efficacy without evidence of immune-suppressing side effects,” Yancopoulos said. “We continue to evaluate the role of IL-4 and IL-13 signaling in related inflammatory conditions, including asthma and nasal polyposis, where we have ongoing dupilumab clinical development.”

Currently in the United States, the FDA has granted Breakthrough Therapy designation of dupilumab.

“We plan to submit a regulatory application in the third quarter of this year and will work to bring this innovative therapy to patients as quickly as possible," said Elias Zerhouni, MD, President, Global R&D, Sanofi.