Dupilumab’s skin story

 

The positive results from a Phase 2b dose ranging study were announced by Sanofi and Regeneron Pharmaceuticals. The drug, dupilumab, is an investigational monoclonal antibody that blocks the action of two proteins involved in inflammation: interleukin-4 and interleukin-13, two cytokines that play a key role in atopic dermatitis (AD), a serious, chronic form of eczema. AD is a common skin disease with troubling signs that include severely dry skin, red lesions that may crust or ooze, skin thickening and symptoms of intense itching that may lead to skin wounds, infections and sleep disturbance. 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.

 

“These clinical data, coupled with our Phase 2a results in asthma last year, support the growing scientific evidence that the IL4/IL-13 pathway may be a fundamental driver in allergic diseases,” said Dr. George D. Yancopoulos, 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 2b 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 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.

 

The most common adverse event 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.

 

“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 Dr. Elias Zerhouni, president of global research and development for 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 3 studies, which we anticipate to begin later this year.”

 

This Phase 2b 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, 300 mg every other week, 300 mg monthly, 200 mg every other week or 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 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.

 

“The New England Journal of Medicine publication brings important attention to moderate-to-severe atopic dermatitis, a common, chronic skin condition characterized by severe itching that can have a significant negative impact on a patient’s ability to lead a full and active life,” said lead author Beck. “We are encouraged by the consistent findings across these earlier studies and look forward to further clinical investigation with dupilumab.”