Clinical Trials

Date: 2014-07-09

Type of information: Publication of results in a medical journal

phase: 2b

Announcement: publication of results in the New England Journal of Medicine

Company: Sanofi (France) Regeneron Pharmaceuticals (USA)

Product: dupilumab

Action mechanism:

• monoclonal antibody. Dupilumab is a fully-human monoclonal antibody that is directed against the shared IL-4R alpha subunit, which blocks signaling from both IL-4 and IL-13. Dupilumab was created using Regeneron's VelocImmune® technology and is being co-developed with Sanofi in atopic dermatitis, asthma and nasal polyposis.

Disease: moderate-to-severe atopic dermatitis

Therapeutic area: Dermatological diseases - Immunological diseases - Inflammatory diseases

Country:

Trial details:

• 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, 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. The four placebo-controlled studies published in the NEJM are NCT01259323, NCT01385657, NCT01639040, NCT01548404.

Latest news:

• • On July 9, 2014, Regeneron Pharmaceuticals and Sanofi announced positive results from a Phase 2b dose-ranging study of dupilumab in adult patients with 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. 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 (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). Sanofi and Regeneron now anticipate to begin phase 3 studies later this year.
• The New England Journal of Medicine publication includes data from four placebo-controlled studies, which all evaluated weekly subcutaneous doses of dupilumab. This included a Phase 2a 12-week monotherapy study, a Phase 2a, four-week study of dupilumab in combination with topical glucocorticoids and two Phase 1 four-week monotherapy studies. In these studies, the most common AEs 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 pruritus (itching).

Is general: Yes