Paris, France, and Tarrytown, N.Y., – June 6, 2016 – Sanofi and Regeneron “outed” the results of a one-year phase 3 study announcing that dupilumab has met its primary and secondary goals in the treatment of inadequately controlled moderate-to-severe atopic dermatitis. The drug, when used in combination with topical corticosteroids (TCS), has shown superiority over the conventional therapy with TCS alone. Essentially, Dupilumab with TCS treatment has been shown to be better than TCS treatment alone.
In a press-release issued a few hours ago, the company released the data from the long-term phase 3 trial called Liberty Ad Chronos. The study was conducted in adult patients with moderate-to-severe atopic dermatitis which was poorly controlled by TCS with or without topical calcineurin inhibitor (TCI). When dupilumab was added to the regimen, it exhibited superiority over the placebo with TCS.
George D. Yancopoulos, Chief Scientific Officer of Regeneron and President of Regeneron Laboratories said, “These are (sic) the first long-term Phase 3 data that demonstrated dupilumab with topical corticosteroids was superior to topical corticosteroids alone, and provided sustained efficacy, significantly improving measures of overall disease severity, skin clearing, itching, and quality of life through one year of treatment.”
While topical corticosteroids are the gold standard for atopic dermatitis, they are non-specific anti-inflammatory agents. Dupilumab, on the other hand, is a targeted therapy specifically blocking the IL-4/IL-13 signaling pathway. The researchers at Sanofi believe this pathway to be the root cause in atopic dermatitis, asthma and nasal polyposis.
About Liberty Ad Chronos Trial
The trial enrolled a total of 740 adult patients; all of whom had moderate-to-severe atopic dermatitis that was inadequately controlled with topical medications. The patients were assessed via the 5-point Investigator’s Global Assessment (IGA) scale, with 0 indicating no disease (clear) and 4 indicating severe inflammation. Patients enrolled in the study had a baseline score of 3 or 4.
All patients initiated daily treatment with a medium potency TCS or low potency TCS.
Patients were randomized into three groups; dupilumab group (300 mg) receiving the drug subcutaneously once per week (n=319), dupilumab (300 mg) group receiving the drug subcutaneously every two weeks (n=106) and placebo group (n=315) receiving the standard placebo with TCS therapy.
In the United States, the primary endpoint of the study was the percentage of patients achieving IGA 0 or 1 at 16 weeks. In Europe and Japan, there was an additional endpoint- the percentage of patients achieving an Eczema Area and Severity Index (EASI) 75 score at week 16. The primary analysis was pre-specified to occur at 52 weeks.
Results and Interpretations
Of patients receiving dupilumab and TCS every two weeks, 39% achieved the primary end point, i.e. clearing or near-clearing of skin lesions (IGA 0 or 1). In contrast, only 12% of the patients receiving placebo with TCS met the primary endpoint.
As for the EASI-75 target, 64% of patients receiving dupilumab weekly with TCS, and 69% of patients receiving dupilumab every two weeks with TCS achieved the target. In contrast, only 23% of the patients receiving placebo with TCS met the target.
Compared to placebo with TCS group, patients in the dupilumab with TCS groups were less likely to discontinue therapy, i.e. 33% vs 15%.
Dupilumab With TCS
Dupilumab is an innovative human investigational monoclonal antibody that imparts its efficacy by activating IL-4/IL-13 pathway. It has shown a favorable safety profile in two pivotal Phase 3 studies for moderate- to- severe atopic dermatitis. It is devoid of the side-effects typically exhibited by immune-suppressing therapies.
Granted in November 2014, Dupilumab enjoys a ‘Breakthrough Therapy’ designation by the U.S. Food and Drug Administration (FDA). However, it is currently under clinical development. The FDA has not evaluated its safety and efficacy yet. Regeneron and Sanofi, in commercial collaboration, will submit the dossier for the drug in the third quarter (Q3) of the current year.
Dupilumab has also shown efficacy against moderate-to-severe asthma in Phase II-B trials by Sanofi.
Sanofi, one of the most renowned global pharmaceutical companies, discovers, develops and distributes therapeutic solutions worldwide. It has five global business units, namely Diabetes and Cardiovascular, Sanofi Genzyme, General Medicines and Emerging Markets, Merial and Sanofi Pasteur.
Sanofi Genzyme is dedicated to developing specialty treatments for debilitating diseases that are difficult to diagnose and treat. Dupilumab is currently being investigated under Genzyme’s capacity.
About Regeneron Pharmaceuticals, Inc.
Regeneron is a biopharmaceutical company based in New York that discovers, invents, manufactures, and markets drugs for the treatment of serious medical conditions. These include eye diseases, high LDL cholesterol, atopic dermatitis, cancer, rheumatoid arthritis, asthma, rare inflammatory conditions and inflammation.
About Atopic Dermatitis
Atopic dermatitis is a chronic inflammatory disease characterized by itchy, inflamed skin. It is strongly linked with family history and people with atopic dermatitis usually have a family history of asthma or hay fever. AD can appear on any part of the body.
Corticosteroids remain the gold standard for the treatment of AD. However, steroids are only the ‘management’ and not a ‘cure’. The treatment focuses on subsiding symptoms of itchiness, inflammation and scaly skin. The condition is chronic and keeps coming back, with steroid therapy providing temporary relief only. There is currently no definitive cure for atopic dermatitis.
Approximately 1.6 million Americans have atopic dermatitis. The approval and ultimate availability of dupilumab may address this unmet medical need by providing an effective treatment.