Regeneron and Sanofi Announce Positive Results from Phase IIb Study of Dupilumab for Atopic Dermatitis

07/15/2014

Regeneron Pharmaceuticals, Inc. and Sanofi announced positive results from a Phase IIb dose-ranging study of dupilumab for moderate to severe atopic dermatitis. All doses of dupilumab met the primary endpoint of a greater improvement in Eczema Area and Severity Index (EASI) scores from baseline compared to placebo. In addition, the companies also announced that four earlier clinical studies of dupilumab in moderate to severe atopic dermatitis were published in the New England Journal of Medicine (NEJM).  Dupilumab is an investigational monoclonal antibody that blocks signaling of IL-4 and IL-13, two cytokines that play a key role in the pathogenesis of moderate to severe atopic dermatitis.

"These clinical data, coupled with our Phase IIa results in asthma last year, support the growing scientific evidence that the IL-4/IL-13 pathway may be a fundamental driver in allergic diseases," said George D. Yancopoulos, MD, PhD, Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. "Blocking IL-4/IL-13 signaling may provide an important new approach to atopic conditions, including asthma, atopic dermatitis and nasal polyposis, where we have ongoing clinical programs."

In the Phase IIb trial, all five subcutaneous doses of dupilumab showed a dose-dependent improvement in the primary endpoint, the mean percent change in EASI score from baseline to week 16.  The improvements in EASI score ranged from a high of 74 percent for patients in the highest dose group, who received 300 milligrams (mg) weekly, to a low of 45 percent in patients who received the lowest dose of 100 mg monthly, compared to 18 percent for patients in the placebo group (p < 0.0001 for all doses).

The most common adverse event (AE) in the Phase 2b study was nasopharyngitis, which was balanced across dupilumab treatment groups (18.5 to 23 percent) compared to placebo (21 percent). Injection site reactions were more frequent in the dupilumab group (5 to 9.5 percent) compared to placebo (3 percent), as was headache (12 to 15 percent) compared to placebo (8 percent).

Dupilumab-treated patients showed highly statistically significant and dose-dependent improvements in additional key efficacy measures compared to placebo after 16 weeks of treatment:

·      12 percent to 33 percent of dupilumab-treated patients achieved clearing or near-clearing of skin lesions, as measured by an investigator's global assessment (IGA) score of 0 or 1, compared to 2 percent with placebo. (p=0.02 to p < 0.0001)

·      Dupilumab-treated patients experienced a 16.5 percent to 47 percent mean reduction in itching, as measured by the pruritus numerical-rating scale (NRS) score, compared to an increase of 5 percent in the placebo group.  (p=0.0005 to p< 0.0001)

"Atopic dermatitis is known to have a profoundly negative effect on quality of life and people with more severe forms of this disease have limited therapeutic choices," said

Elias Zerhouni, MD, President, Global R&D, Sanofi. "These latest results are consistent with what was observed in the earlier clinical studies and add to the body of evidence that investigational dupilumab may have a role to play for patients with moderate to severe atopic dermatitis. We are now able to select the optimal doses for the Phase III studies, which we anticipate to begin later this year."

This Phase IIb double-blind, placebo-controlled, 16-week, dose-ranging study randomized 380 patients with moderate-to-severe atopic dermatitis, who could not be adequately controlled with topical medication or for whom topical treatment was not advisable. Patients were randomized to receive one of five doses of dupilumab (300 mg weekly, 300mg every other week, 300mg monthly, 200 mg every other week, 100 mg monthly) or placebo.  Patients in the study had approximately 50 percent of their skin affected by atopic dermatitis at baseline.  Within the past year, approximately 35 percent of patients received an oral corticosteroid and approximately 20 percent received a systemic non-steroid immunosuppressant for AD. Approximately 60 percent of patients had another allergic condition, including approximately 40 percent of patients who had a history of asthma. The follow-up period of the study is ongoing and patients will be followed for 16 weeks after treatment.

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