Regeneron Pharmaceuticals and Sanofi said their eczema drug candidate dupilumab is headed for Phase III studies after meeting its primary endpoints of reduced disease severity and skin clearing in a Phase IIb trial.
All doses of dupilumab met the primary endpoint of greater improvement in the Eczema Area and Severity Index (EASI) scores from baseline compared to placebo in in adult patients with a serious, chronic form of eczema, moderate-to-severe atopic dermatitis, the companies said. Patients in the study had approximately half of their skin affected by atopic dermatitis at baseline.
Improvements in EASI score ranged from a high of 74% for patients in the highest dose group, who received 300 mg weekly, to a low of 45% in patients who received the lowest dose of 100 mg monthly, compared to 18% for patients receiving placebo. 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, 100 mg monthly) or placebo.
Dupilumab is a monoclonal antibody designed to block the signaling of IL-4 and IL-13, two cytokines that play a key role in the pathogenesis of moderate-to-severe atopic dermatitis. In the Phase IIb trial, Dupilumab-treated patients showed additional dose-dependent yet statistically significant improvements in additional measures compared to placebo after 16 weeks:
12% to 33% of dupilumab-treated patients achieved clearing or near-clearing of skin lesions, as measured by an investigator's global assessment score of 0 or 1, compared to 2% with placebo.
Dupilumab-treated patients experienced a 16.5% to 47% mean reduction in itching, as measured by the pruritus numerical-rating scale score, compared to a 5% increase in placebo patients.
The most common adverse event was nasopharyngitis, which was balanced across dupilumab treatment groups (18.5% to 23%) compared to placebo (21%). Injection site reactions were more frequent in the dupilumab group (5% to 9.5%) compared to placebo (3%), as was headache (12% to 15%) compared to placebo (8%).
"These clinical data, coupled with our mid-stage 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," George D. Yancopoulos, M.D., Ph. D., Regeneron’s CSO and president of Regeneron Laboratories, said in a statement. " 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."
Added Elias Zerhouni, M.D., Sanofi’s president, Global R&D: "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.”
According to ClinicalTrials.gov, Sanofi and Regeneron were recruiting patients as of June 19 for a Phase III trial (NCT 02134028) designed to assess the long-term safety and tolerability of dupilumab in patients with asthma who participated in a previous dupilumab asthma study. The study’s secondary objectives include evaluating dupilumab’s effect on those patients with respect to systemic exposure, anti-drug antibodies, and biomarkers.
Regeneron and Sanofi are counting on dupilumab to deliver on analyst forecasts of blockbuster sales. Last year, Leerink Swann analyst Joseph Schwartz told Reuters he predicted that dupilumab would capture peak annual sales of $2.8 billion for asthma and atopic dermatitis indications.
The Phase IIb study assessed the effects of dupilumab over 16 weeks on a randomized 380 patients who could not be adequately controlled with topical medication or for whom topical treatment was not advisable. Within the past year, approximately 35% of patients received an oral corticosteroid, while about 20% received a systemic immunosuppressant for atopic dermatitis. Approximately 60% of patients had another allergic condition, including approximately 40% 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 companies said.
Additionally, results from four earlier clinical trials for dupilumab were published yesterday in the New England Journal of Medicine. The journal featured data from four placebo-controlled studies, each evaluating weekly subcutaneous doses of the experimental drug—a Phase IIa 12-week monotherapy study, a Phase IIa, four-week study of dupilumab in combination with topical glucocorticoids and two Phase I, four-week monotherapy studies.
In these studies, according to Regeneron and Sanofi, the most common adverse events were nasopharyngitis and headache, which occurred with a higher frequency in the dupilumab group. Treatment with dupilumab, either as a monotherapy or in combination, was associated with improvement in skin lesions and substantial improvements in itching.
"We are encouraged by the consistent findings across these earlier studies and look forward to further clinical investigation with dupilumab," said Lisa Beck, M.D., Department of Dermatology, University of Rochester Medical Center and lead author of the NEJM paper.