Two phase III, placebo-controlled studies evaluating dupilumab (Regeneron Pharmaceuticals/Sanofi) in adults with inadequately controlled moderate-to-severe atopic dermatitis (AD) have 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. The patients were enrolled if they were not adequately controlled with topical medications or if topical treatment was not medically advisable. All of the patients were evaluated via the five-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.
The patients were randomly assigned to one of three treatment groups: subcutaneous (SC) dupilumab 300 mg once per week, SC dupilumab 300 mg every two weeks, or placebo for 16 weeks after an initial SC dupilumab loading dose of 600 mg or placebo. The results at 16 weeks included the following:
- For SOLO 1 and SOLO 2, respectively, 37% and 36% of patients who received dupilumab 300 mg weekly and 38% and 36% of patients who received dupilumab 300 mg every two weeks achieved clearing or near-clearing of skin lesions (IGA score of 0 or 1), compared with 10% and 8.5% with placebo (P < 0.0001). This was the study’s primary endpoint in the U.S.
- For SOLO 1 and SOLO 2, respectively, the percent improvements in EASI from baseline were 72% and 69% in patients who received the 300-mg weekly dose and 72% and 67% in patients who received dupilumab 300 mg every two weeks, compared with 38% and 31% for placebo (P < 0.0001).
- For SOLO 1 and SOLO 2, respectively, 52.5% and 48% of patients who received dupilumab 300 mg weekly and 51% and 44% of patients who received dupilumab 300 mg every two weeks achieved EASI-75 compared with 15% and 12% of the placebo-treated patients (P < 0.0001). This was the key secondary endpoint in the U.S.
For the 16-week treatment period, the overall rates of adverse events were comparable between the dupilumab groups and the placebo groups (65% and 73% versus 65% and 72%, respectively). The proportions of patients who completed the treatment period were 88% and 94% for dupilumab, and 80.5% and 82% for placebo. The rates of serious adverse events were 1% and 3% for dupilumab, and 5% and 6% for placebo. Rates of serious and severe infections were also numerically higher in the placebo groups in both studies (0.5% and 1% for dupilumab versus 2% and 3% for placebo). Adverse events that had a higher rate with dupilumab treatment across both studies included injection-site reactions (10% and 20% percent for dupilumab versus 7% and 8% for placebo) and conjunctivitis (7% and 12% for dupilumab versus 2% and 2% for placebo); approximately 26% of patients in both studies reported a history of allergic conjunctivitis at study entry. No patients discontinued therapy because of injection-site reactions, and one patient discontinued therapy because of conjunctivitis.
The FDA granted a breakthrough therapy designation to dupilumab in November 2014. The treatment is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
Source: Regeneron; April 1, 2016.