Dupixent (dupilumab) is used to treat moderate-to-severe atopic dermatitis (eczema) in patients aged six years and older and moderate-to-severe asthma in patients aged 12 years and older.
Developed jointly by Sanofi and Regeneron, Dupixent is administered as a subcutaneous injection.
Regulatory approvals for Dupixent
The US Food and Drug Administration (FDA) granted breakthrough therapy designation to Dupixent for uncontrolled atopic dermatitis in 2014.
The FDA accepted a biologics license application (BLA) for the drug in September 2016 and granted approval for the treatment of patients with moderate-to-severe atopic dermatitis in March 2017.
Dupixent also received a marketing authorisation for the drug in the EU to treat atopic dermatitis in adult patients in September 2017, as well as approval in Canada and Japan.
In October 2018, the FDA approved the drug as an add-on maintenance therapy to treat moderate-to-severe asthma in patients aged 12 years and over with oeosinophilic phenotype or oral corticosteroid-dependent asthma.
In November 2018, the FDA accepted a supplemental BLA for the drug under priority review status to treat adolescent patients aged between 12 and 17 years with moderate-to-severe atopic dermatitis. Approval was granted in March 2019.
The FDA approved the drug for the treatment of atopic dermatitis in children aged six to 11 years in May 2020, making it the first biologic medicine for this patient population. Dupixent was subsequently approved for the same patient population in Europe in November 2020.
In March 2021, the FDA accepted a supplemental BLA for the drug as an add-on treatment for uncontrolled moderate to severe asthma in children aged six to 11 years. The target action date is set for 21 October 2021.
Atopic dermatitis condition and symptoms
Atopic dermatitis is a long-term chronic form of eczema and is commonly seen in people with 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 the skin, together 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 the skin formed due to irritation and scratching.
The disease is most commonly seen in infants aged 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, as well as around the neck, hands and feet.
An estimated seven to eight million adults in the US are affected with a moderate-to-severe form of atopic dermatitis.
Dupixent’s mechanism of action
Dupixent is a monoclonal antibody (mAb) that targets the interleukin-4 (IL-4) receptor alpha subunit (IL-4Rα) and blocks the intercellular signalling of IL-4 and IL-13, cytokines that help maintain the immune response of Th2 cells.
IL-4 and IL-13 drive the type 2 inflammation that plays a crucial role in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and oeosinophilic oesophagitis.
The drug blocks IL-4 and IL-13 signalling and successfully mitigates the symptoms of atopic dermatitis and asthma.
Clinical trials on Dupixent
The FDA’s initial approval of the drug for moderate to severe atopic dermatitis in adults was based on results from the global Liberty AD clinical programme, which included around 3,000 patients in Phase III trials SOLO I, SOLO II and CHRONOS.
CHRONOS was a Phase III, randomised, double-blind, placebo-controlled, multi-national trial conducted to evaluate the drug’s efficacy and safety. It enrolled 740 adult patients with moderate-to-severe atopic dermatitis who had initially been treated with medium-potency topical corticosteroids (TCS) or low-potency topical corticosteroids (TCS).
Subjects in the trial were divided into three treatment arms, which received either dupilumab 300mg once a week, dupilumab 300mg every two weeks, or placebo. The study met its primary and secondary endpoints and dupilumab with TCS improved the overall disease severity at week 16 and 52 compared with placebo.
SOLO I and SOLO II were two identical Phase III trials conducted on 1,379 patients with moderate-to-severe atopic dermatitis to examine the drug’s efficacy and safety.
The subjects were divided into three treatment arms, receiving either dupilumab 300mg once a week, dupilumab 300mg every two weeks, or placebo for 16 weeks after an initial dupilumab dose of 600mg or placebo.
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 trials, subjects who received dupilumab 300mg once a week and 300mg for every two weeks achieved clearing or near clearing of skin lesions, as well as EASI-75 at week 16 compared with the subjects who received the placebo.
The trials also demonstrated that treatment with dupilumab reduced disease severity and itching and improved both the quality of life and mental health of patients.
The FDA’s approval of Dupixent as an add-on maintenance therapy for moderate and severe asthma patients was based on results from pivotal randomised, placebo-controlled, multi-centre clinical trials named Trial I, Trial II and Trial III.
The pivotal trials evaluated the drug’s safety and efficacy in 2,888 adult and adolescent patients suffering from moderate-to-severe asthma.
The drug reduced the exacerbations and improved lung function in the patients in Trial I. Severe exacerbations were reduced by 67% compared with placebo and lung functions by 29% to 33% compared with 14% to 16% in patients who received the placebo.
In Trial III, Dupixent reduced the use of average daily oral corticosteroid by 70% compared with 42% in patients treated with placebo. More than 50% of Dupixent-treated patients completely eliminated the use of oral corticosteroids.