Regeneron, Sanofi report positive results from Phase 2b study dupilumab with moderate to severe AD -
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN ) and Sanofi (EURONEXT: SAN and NYSE: SNY ) announced today positive results of a dose ranging study phase 2b dupilumab, an experimental treatment in patients adults with moderate to severe atopic dermatitis (AD), a severe form, chronic eczema. All dupilumab doses have reached the primary endpoint of a greater improvement in Eczema Area Severity Index (EASI) Baseline scores compared to placebo. In addition, the companies also announced that four clinical studies of previous dupilumab in moderate to severe atopic dermatitis were published today in the New England Journal of Medicine (NEJM). Dupilumab is an investigational monoclonal antibody that blocks the signaling of IL-4 and IL-13, cytokines that play a key role in the pathogenesis of moderate to severe atopic dermatitis.
"These clinical data, coupled with our Phase 2a results in asthma last year, support the scientific evidence increasingly as IL-4 / IL-13 pathway may be a fundamental factor in allergic diseases, "said George D. Yancopoulos, MD, Ph. D., Chief scientific Officer of Regeneron and President of Regeneron Laboratories. "Blocking the IL-4 / IL-13 signaling may provide an important new approach for atopic conditions including asthma, atopic dermatitis and nasal polyposis, where we have clinical programs underway."
In the Phase 2b trial, all five subcutaneous doses of dupilumab showed a dose-dependent improvement in the primary endpoint, the percent change in the average baseline EASI score at week 16 . improvements in EASI score ranged from a high of 74 percent for patients in the group receiving the highest dose, which received 300 milligrams (mg) per week, a minimum of 45 percent in patients who have received the lowest dose of 100 mg per month, compared with 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 were nasopharyngitis, which was balanced across treatment groups dupilumab (18.5 to 23 percent) compared to placebo (21 percent). reactions at the injection site were more frequent in the group dupilumab (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 a statistically significant and dose-dependent improvement in other key efficacy measures compared to placebo after 16 weeks of treatment:
- 12 percent to 33 percent of patients treated with dupilumab compensation or almost clearing the skin lesions as measured by global assessment (IGA) score a investigator of 0 or 1, compared to 2 percent with placebo. (P = 0.02 to P <0.0001)
- dupilumab patients treated experienced a 16.5 percent to 47 percent average reduction in itch as measured by pruritus numerical rating scale (NRS) score compared with an increase of 5 percent in the placebo group. (P = 0.0005 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 treatment options, "said Elias Zerhouni, MD, President, global R & D, Sanofi." These results are consistent with what was observed in previous clinical studies and add to the body of evidence that experimental dupilumab may have a role in patients with moderate to severe atopic dermatitis. We are now able to select the optimal dose for the phase 3 studies, we plan to begin later this year. "
this Phase 2b, double-blind, placebo-controlled, 16-week, the dose ranging study randomized 380 patients with moderate to severe atopic dermatitis, which could not be adequately controlled with topical medications or where a topical treatment was not advised. Patients were randomized to receive one of five doses of dupilumab (300 mg per week, 300 mg every two weeks, 300 mg per month, 0 mg every two weeks, 100 mg per month) or placebo. Patients in the study had about 50 percent of their skin affected by atopic dermatitis at baseline. In the past year, about 35 percent of patients received oral corticosteroids and about 20 percent received a non-steroidal systemic immunosuppressant for AD. About 60 percent of patients had another allergic condition, about 40 percent of patients who had a history of asthma. The period of follow-up study is underway and patients will be followed for 16 weeks after treatment.
The NEJM dupilumab moderate to severe atopic dermatitis Publication
The New England Journal of Medicine publication includes data from four placebo-controlled studies, which all evaluated doses weekly subcutaneous of dupilumab. This included a 12-week study of Phase 2a monotherapy, a phase 2a, four weeks dupilumab study in combination with topical glucocorticoid and two Phase 1 monotherapy four weeks. In these studies, the most common adverse events were nasopharyngitis and headache, which occurred with a higher frequency in the dupilumab group. Dupilumab treatment, either as monotherapy or in combination, was associated with improvement of skin lesions and substantial improvements in pruritus (itching). The full publication is available at www.nejm.org.
"The New England Journal of Medicine publication brings important attention to the moderate to severe atopic dermatitis, a condition common, chronic skin condition characterized by severe itching that can have a significant negative impact on the ability of a patient to lead full and active lives, "said Lisa Beck, MD, Department of Dermatology, University of Rochester Medical Center and lead author of the NEJM paper." We are encouraged by the consistent results in these earlier studies and have look forward to further clinical research with dupilumab. "
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