Dupixent (dupilumab) for the Treatment of Atopic Dermatitis, France
Dupixent (dupilumab) is an investigational drug being developed by Sanofi and Regeneron as a treatment for moderate to severe atopic dermatitis in adult patients.
The US Food and Drug Administration (FDA) granted breakthrough therapy designation to Dupixent for uncontrolled atopic dermatitis in 2014.
The FDA accepted the biologics license application (BLA) for the drug on 26 September 2016 and the application is under priority review with an expected Prescription Drug User Fee Act (PDUFA) date of 29 March 2017.
Atopic dermatitis condition and symptoms
Atopic dermatitis is a long-term chronic form of eczema and is commonly seen in people with very sensitive skin and a malfunctioning immune system. The disease results from an allergic response generated by a subset of immune cells known as Type 2 helper T cells (Th2).
The skin infection is characterised by inflammation of skin along with itchy, red, swollen cracks, oozing and crusting blisters, dry skin, ear discharge or bleeding, change in skin colour, and thickened or leather-like patches on skin formed due to irritation and scratching.
The disease is most commonly seen in infants younger than two years with itchy and scaly rashes on the face, scalp, hands, and feet. In adults with atopic dermatitis, rashes are often developed inside the knees and elbow and also around the neck, hands, and feet.
An estimated seven to eight million adults in the US are affected with moderate to severe form of atopic dermatitis.
Dupixent's mechanism of action
Dupixent is a monoclonal antibody that targets the interleukin-4 (IL-4) receptor alpha subunit (IL-4Ra) and blocks the intercellular signalling of IL-4 and IL-13.
IL-4 and IL-13 are the major cytokines that play an important role in maintaining the immune response of Th2 cells. The drug blocks IL-4 and IL-13 signalling and successfully mitigates the symptoms of atopic dermatitis.
Clinical trials on Dupixent
The BLA for dupilumab was submitted to the US FDA based on results obtained from the Liberty AD clinical programme, which included three phase III trials SOLO 1, SOLO 2, and CHRONOS.
CHRONOS was a phase III, randomised, double-blind, placebo-controlled, multi-national trial conducted to evaluate the efficacy and safety of the drug. The trial enrolled 740 adult patients with moderate to severe atopic dermatitis, who were initially treated with medium-potency topical corticosteroids (TCS) or low-potency topical corticosteroids (TCS).
The subjects in the trial were divided into three treatment arms. These received either dupilumab 300mg once a week, dupilumab 300mg every two weeks, or placebo. The study met the primary and secondary endpoints and, when compared to placebo, dupilumab with TCS improved the overall disease severity at week 16 and 52.
SOLO 1 and SOLO 2 were two identically designed phase III trials conducted on 1,379 patients with moderate to severe atopic dermatitis to examine the efficacy and safety of the drug.
The subjects were divided into three treatment arms, which received either dupilumab 300mg once a week, dupilumab 300mg for every two weeks, or placebo for 16 weeks after an initial dupilumab dose of 600mg or placebo.
The subjects in the trial were assessed on a five-point Investigator's Global Assessment (IGA) scale and Eczema Area and Severity Index (EASI).
In both the trials, subjects who received dupilumab 300mg once a week and 300mg for every two weeks achieved clearing or near clearing of skin lesions and achieved EASI-75 at week 16 compared to the subjects who received placebo.
The trials also demonstrated that treatment with dupilumab reduced disease severity and itching and improved both quality of life and mental health of the patients.