Regeneron Pharmaceuticals, Inc. and Sanofi announced that a one-year phase 3 study, known as LIBERTY AD CHRONOS, evaluating investigational dupilumab met its primary and key secondary endpoints. In the study, dupilumab with topical corticosteroids (TCS) was compared to TCS alone in moderate-to-severe atopic dermatitis (AD) adult patients. Patients in the study were inadequately controlled by topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI). Dupilumab with TCS significantly improved measures of overall disease severity at 16 and 52 weeks, when compared to placebo with TCS.

"This is the first long-term phase 3 data that demonstrated dupilumab with topical corticosteroids was superior to topical corticosteroids alone, and provided sustained efficacy, significantly improving measures of overall disease severity, skin clearing, itching, and quality of life through one year of treatment," said George D. Yancopoulos, M.D., Ph.D., chief scientific officer of Regeneron and president of Regeneron Laboratories. "Although topical corticosteroids are standard therapies for atopic dermatitis, they are non-specific anti-inflammatory agents, while dupilumab is a targeted therapy that specifically blocks the IL-4/IL-13 signaling pathway. Our collective clinical data demonstrate that this pathway is a root cause in atopic dermatitis, asthma and nasal polyposis and we continue to evaluate the potential of this pathway in these atopic and allergic diseases."

"Dupilumab is an innovative first-in-class investigational agent that has shown significant efficacy and a favorable safety profile in two pivotal phase 3 studies in monotherapy for moderate-to-severe atopic dermatitis, and now in concomitant administration with topical corticosteroids," said Elias Zerhouni, M.D., president, global R&D, Sanofi. "These one-year data strengthen the earlier 16-week results, suggesting that dupilumab impacts the aberrant activation of the IL-4/IL-13 pathway which resulted in significant efficacy without the side effects associated with immune-suppressing therapies. We will continue to advance dupilumab for patients worldwide suffering from inadequately controlled moderate-to-severe atopic dermatitis, with the first submission planned in the US for the third quarter of this year."

The primary endpoint results at week 16 were the following:

39 percent of patients who received either dupilumab 300 mg weekly with TCS or dupilumab 300 mg every two weeks with TCS achieved clearing or near-clearing of skin lesions (IGA 0 or 1), compared to 12 percent of patients receiving placebo with TCS (p less than 0.0001).

64 percent of patients who received dupilumab 300 mg weekly with TCS, and 69 percent of patients who received dupilumab 300 mg every two weeks with TCS achieved EASI-75, a 75 percent reduction on an index measuring eczema severity, compared to 23 percent of patients receiving placebo with TCS (p less than 0.0001).

The secondary endpoint 52-week results were the following:

40 percent of patients who received dupilumab 300 mg weekly with TCS, and 36 percent of patients who received dupilumab 300 mg every two weeks with TCS achieved clearing or near-clearing of skin lesions (IGA 0 or 1), compared to 12.5 percent of patients receiving placebo with TCS (p less than 0.0001).

64 percent of patients who received 300 mg weekly with TCS, and 65 percent of patients who received 300 mg every two weeks with TCS achieved EASI-75, compared to 22 percent with placebo with TCS (p less than 0.0001).

Patients were less likely to discontinue therapy in the dupilumab with TCS groups compared to placebo with TCS group (15 percent in both dupilumab groups; 33 percent placebo).

The overall rate of adverse events was comparable between the dupilumab with TCS groups (83 percent for the weekly dose (qw) and 88 percent for the every two weeks (q2w) dosing group) and the placebo with TCS group (84 percent). The rate of serious adverse events was comparable between the dupilumab with TCS groups (3 (qw) and 4 percent (q2w)) and placebo with TCS group (5 percent). Serious and/or severe infections were numerically higher in the placebo with TCS group (1 percent in both dupilumab groups and 2 percent placebo). Adverse events that were noted to have a higher rate with dupilumab included injection site reactions (20 (qw) and 16 percent (q2w) dupilumab; 9 percent placebo) and conjunctivitis (19 (qw) and 13 (q2w) percent dupilumab; 8 percent placebo); 22 percent of patients on placebo, and 23 (qw) and 28 percent (q2w) of patients on dupilumab reported a history of allergic conjunctivitis at study entry.

More detailed results, including long-term efficacy and safety data from CHRONOS 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. If approved, dupilumab would be commercialized by Regeneron and Sanofi Genzyme, the specialty care global business of Sanofi.

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

A total of 740 adult patients with moderate-to-severe AD were enrolled in CHRONOS. All patients were inadequately controlled with topical medications and 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. All patients initiated daily treatment with a medium potency TCS or low potency TCS on areas of the body where medium potency TCS is considered unsafe. Patients were randomized in a 3:1:3 fashion into the following treatment groups (all in combination with TCS): dupilumab 300 mg subcutaneously once per week (n=319), dupilumab 300 mg subcutaneously every two weeks (n=106), or placebo (n=315). This design allowed sufficient power for the efficacy endpoints in both dupilumab groups while increasing the available safety data on the more frequent dosing regimen. In the U.S., the primary efficacy endpoint of the study was the percent of patients who achieved IGA 0 or 1 at 16 weeks. In Europe and Japan there was an additional co-primary endpoint: the percent of patients achieving an EASI 75 score at week 16. The primary analysis was pre-specified to occur 52 weeks after approximately 85 percent of patients were randomized into the study.

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 inflammation. About 70 percent of people with atopic dermatitis have a family history of other common atopic diseases, such as asthma or hay fever. In many cases, atopic dermatitis is characterized by pruritus (itchiness) and skin lesions. The intense itching, scratching and skin damage associated with the disease can cause secondary infections that may require additional treatments. In addition, the physical manifestations of the disease can lead to anxiety, depression, and feelings of social isolation. Based on a survey of 200 physicians, there are approximately 1.6 million patients in the U.S. that have been diagnosed with moderate-to-severe atopic dermatitis, and are currently being treated but still are living with inadequately controlled disease.