Date: 2016-06-06
Type of
information: Results
phase: 3
Announcement: results
Company: Sanofi (France) Regeneron Pharmaceuticals (USA - NY)
Product: dupilumab
Action
mechanism:
- monoclonal antibody. Dupilumab, a fully-human monoclonal antibody, is directed against the IL-4 receptor alpha subunit, which blocks signaling from both IL-4 and IL-13. IL-4 and IL-13 are key cytokines that are required for the initiation and maintenance of the Th2 (Type 2 helper T-cell) immune response, which is believed to be a critical pathway in allergic inflammation.
Dupilumab was created using Regeneron's pioneering VelocImmune® technology and is being co-developed with Sanofi in atopic dermatitis, asthma and chronic sinusitis with nasal polyps.
Disease: moderate-to-severe atopic dermatitis
Therapeutic
area: Dermatological diseases - Inflammatory diseases
Country: Australia, Canada, Czech Republic, France, Germany, Hungary, Italy, Japan, Republic of Korea, Latvia, The Netherlands, New Zealand, Poland, Romania, Russian Federation, Taiwan, UK, USA
Trial
details:
- LIBERTY AD CHRONOS is a randomized, double-blind, placebo-controlled, multi-national study with the primary objective of demonstrating the efficacy of dupilumab in adults with moderate to severe atopic dermatitis when administered concomitantly with topical corticosteroids through 16 weeks. Secondary objectives of the study will evaluate the long-term safety and efficacy of dupilumab up to 52 weeks. A total of 740 adult patients with moderate-to-severe atopic dermatitis 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. (NCT02260986)
- The LIBERTY AD Phase 3 clinical program consists of five trials of patients with moderate-to-severe atopic dermatitis at sites worldwide.
Latest
news:
- • On June 6, 2016, Regeneron Pharmaceuticals and Sanofi announced that the 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 adult patients. Dupilumab with TCS significantly improved measures of overall disease severity at 16 and 52 weeks, when compared to placebo with TCS.
- 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.
- - 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.
- 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.
- - 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.
- 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.
- • On October 20, 2014, Sanofi and Regeneron Pharmaceuticals announced that the first patients have been dosed in the Phase 3 clinical study LIBERTY AD CHRONOS of dupilumab in adults with moderate-to-severe atopic dermatitis.
Is
general: Yes
