SOLO 1 and 2 trials successful fordupilumab to treat atopic dermatitis- Sanofi + Regeneron

Sanofi and Regeneron Pharmaceuticals, Inc. announced that two placebo-controlled Phase III studies evaluating investigational dupilumab in adult patients with inadequately controlled moderate-to-severe atopic dermatitis (AD) met their primary endpoints. In the studies, known as LIBERTY AD SOLO 1 and SOLO 2 , treatment with dupilumab as monotherapy significantly improved measures of overall disease severity, skin clearing, itching, quality of life, and mental health. A total of 1,379 adult patients with moderate-to-severe AD were enrolled in the identically-designed SOLO 1 and SOLO 2 trials. Patients were enrolled if they were not adequately controlled with topical medications, or if topical treatment was not medically advisable. All patients were assessed via the 5-point Investigator's Global Assessment (IGA) scale, ranging from 0 (clear) to 4 (severe); entry criteria required a baseline score of 3 or 4. Patients were also assessed using the Eczema Area and Severity Index (EASI) and other measures. Patients were randomized into one of three treatment groups: dupilumab 300 mg subcutaneously once per week, dupilumab 300 mg subcutaneously every two weeks, or placebo for 16 weeks following an initial dupilumab loading dose of 600 mg subcutaneously, or placebo. Results at 16 weeks included the following: 1. For SOLO 1 and SOLO 2, respectively, 37 and 36 percent of patients who received dupilumab 300 mg weekly, and 38 and 36 percent of patients who received dupilumab 300 mg every two weeks , achieved clearing or near-clearing of skin lesions (IGA 0 or 1), compared to 10 and 8.5 percent with placebo (p less than 0.0001). This was the primary endpoint of the study in the U.S. 2. For SOLO 1 and SOLO 2, respectively, the percent improvement in EASI from baseline was 72 and 69 percent in patients who received the 300 mg weekly dose, and 72 and 67 percent for patients who received dupilumab 300 mg every two weeks, compared to 38 and 31 percent for placebo (p less than 0.0001). 3.For SOLO 1 and SOLO 2, respectively, 52.5 and 48 percent of patients who received dupilumab 300 mg weekly, and 51 and 44 percent of patients who received dupilumab 300 mg every two weeks, achieved EASI-75 compared to 15 and 12 percent with placebo (p less than 0.0001). This was the key secondary endpoint in the US for these studies and one of the primary endpoints in the EU. For the 16-week treatment period, the overall rate of adverse events (65-73 percent dupilumab and 65-72 percent placebo) was comparable between the dupilumab groups and the placebo groups. The proportion of patients who completed the treatment period was 88-94 percent for dupilumab and 80.5-82 percent for placebo. The rate of serious adverse events was 1-3 percent for dupilumab and 5-6 percent for placebo.

Comment: The atopic dermatitis market is poorly served: current treatments include topical and systemic steroids and the newer calcineurin inhibitors such as Novartis's Elidel (pimecrolimus).

Comment: Regeneron and Sanofi intend to file dupilumab in the US in the third quarter of this year. If successful, dupilumab would be the first approved systemic treatment for the condition, helping to address significant unmet need.