Sanofi, a global healthcare leader, and Regeneron Pharmaceuticals, Inc., a leading science-based biopharmaceutical company, announced that two placebo-controlled phase 3 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.

"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 one million Americans," said George D. Yancopoulos, M.D., Ph.D., chief scientific officer of Regeneron and President of Regeneron Laboratories. "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 - in these 16 week trials, dupilumab blocked the aberrant activation of this pathway, resulting in significant efficacy without evidence of immune-suppressing side effects. 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."

"There are no approved systemic therapies in the US for people with moderate-to-severe atopic dermatitis, underscoring the clear unmet need. These results may bring new hope to AD patients, many of whom have suffered for years," said Elias Zerhouni, M.D., president, global R&D, Sanofi. "In the US, where dupilumab in atopic dermatitis has been granted Breakthrough Therapy designation by the US FDA, 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."

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:

For SOLO 1 and SOLO 2, respectively, 37 and 36 per cent of patients who received dupilumab 300 mg weekly, and 38 and 36 per cent 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 per cent with placebo (p less than 0.0001).  This was the primary endpoint of the study in the US.

For SOLO 1 and SOLO 2, respectively, the per cent improvement in EASI from baseline was 72 and 69 per cent in patients who received the 300 mg weekly dose, and 72 and 67 per cent for patients who received dupilumab 300 mg every two weeks, compared to 38 and 31 per cent for placebo (p less than 0.0001).

For SOLO 1 and SOLO 2, respectively, 52.5 and 48 per cent of patients who received dupilumab 300 mg weekly, and 51 and 44 per cent of patients who received dupilumab 300 mg every two weeks, achieved EASI-75 compared to 15 and 12 per cent 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 per cent dupilumab and 65-72 per cent placebo) was comparable between the dupilumab groups and the placebo groups. The proportion of patients who completed the treatment period was 88-94 per cent for dupilumab and 80.5-82 per cent for placebo. The rate of serious adverse events was 1-3 per cent for dupilumab and 5-6 per cent for placebo. Serious and severe infections were also numerically higher in the placebo groups in both studies (0.5-1 per cent dupilumab and 2-3 per cent placebo).  Adverse events that were noted to have a higher rate with dupilumab treatment across both studies included injection site reactions (10-20 per cent dupilumab; 7-8 per cent placebo), conjunctivitis (7-12 per cent dupilumab; 2 per cent placebo); approximately 26 per cent of patients in both studies reported a history of allergic conjunctivitis at study entry.  No patient discontinued therapy due to injection site reactions and only one patient discontinued therapy due to conjunctivitis.

More detailed results from SOLO 1 and SOLO 2 will be submitted for presentation at a future medical congress.

The US Food and Drug Administration (FDA) granted dupilumab Breakthrough Therapy designation in AD in November 2014. Dupilumab is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.

The LIBERTY AD phase 3 clinical program consists of five trials in patients with moderate-to-severe AD at sites worldwide.

Atopic dermatitis - a serious form of eczema - is a chronic inflammatory disease characterized by itchy, inflamed skin that can be present on any part of the body. Though symptoms appear externally, atopic dermatitis is characterized by underlying systemic inflammation. Atopic dermatitis affects approximately 7-8 million adults in the US and 1 to 3 per cent of adults worldwide. Based on a survey of 200 physicians, there are approximately 1.6 million moderate-to-severe diagnosed and treated patients in the US with uncontrolled disease. About 70 per cent of people with atopic dermatitis have a family history of other common atopic diseases, such as asthma or hay fever. The intense itching, scratching and skin damage associated with the disease can sometimes lead to infections, caused by bacteria, such as Staphylococcus aureus. In addition, the physical manifestations of the disease can lead to anxiety, depression, and feelings of social isolation.