Dupilumab Demonstrates Safety, Efficacy in Pediatric AD Patients Ages 6 Months to 5 Years

Regeneron Pharmaceuticals, Inc. and Sanofi announced positive results from a recent phase 3 trial (LIBERTY AD; NCT03346434), investigating dupilumab (Dupixent) as treatment for moderate to severe atopic dermatitis (AD) in pediatric patients 6 months to 5 years old.¹ It is part of the largest phase 3 clinical trial program in AD, according to the press release.

Dupilumab is a fully human monoclonal antibody that inhibits the signaling of the interleukin (IL)-4 and IL-13 pathways and is not an immunosuppressant.

"When a child is diagnosed with moderate-to-severe atopic dermatitis in the first few months of life, many aspects of their childhood can be significantly impacted. Parents and caregivers are challenged to find safe and effective treatment options," said John Reed, MD, PhD, global head of research and development at Sanofi, Paris, France.

"Currently, the standard of care for this patient population is topical steroids and other immunosuppressive medicines may be used which can damage delicate skin and, if used long-term, potentially impact growth,” he added. “Knowing that safety is of the utmost importance for physicians and parents when considering treatment options for children and infants, we are encouraged by the results of this trial showing Dupixent addressed the signs and symptoms of atopic dermatitis without broadly suppressing the immune system, demonstrating the potential it could have for these very young patients."

The trial met all primary and secondary endpoints, demonstrating that dupilumab in combination with topical corticosteroids (TCS) significantly reduced overall disease severity and improved skin clearance, itch, and health-related quality of life measures at 16 weeks compared to TCS, referred to as placebo, alone.

Dupilumab is the first biologic medicine to show positive results in this population and is the only approved biologic medicine in patients 6 years and older with uncontrolled moderate-to-severe atopic dermatitis.

It was observed during the 16-week period that a lower rate of skin infections was found in the dupilumab arm (12%) vs the placebo arm (24%) and the total number of infections were close to 70% lower. 

Patients in the trial were treated with dupilumab every 4 weeks (200 mg or 300 mg doses based on body weight, with TCS or placebo. The primary endpoints were the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0/1 and a 75% improvement in Eczema Area and Severity Index (EASI 75).

The analysis found that at 16 weeks patients treated with dupilumab:

• 28% achieved clear or almost-clear skin compared to 4% with placebo.
• 53% achieved 75% or greater overall disease improvement from baseline compared to 11% with placebo.
• 70% average improvement from baseline in EASI 75 compared to 20% improvement with placebo.
• 49% average improvement from baseline in itch compared to 2% improvement with placebo.
• Significantly improved measures of observed patient outcomes (including sleep, skin pain and health-related quality of life), as well as caregiver-reported health-related quality of life.

"Moderate-to-severe [AD] in infants and young children is incredibly distressing for patients and their caregivers, who manage painful and persistent itch, intensive daily skincare routines such as chlorine baths and wet wraps, as well as sleepless nights for children and their families," said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron, Tarrytown, New York.

"In fact, when starting this trial, the disease covered more than half of children's bodies and nearly a third of patients had previously resorted to using immunosuppressive medicines,” he continued. “These data show that Dupixent dramatically reduced the impact of atopic dermatitis on the lives of these young children and their families, with rapidly cleared skin, improved itch and improved observed patient outcomes, including sleep and skin pain.”

After 16 weeks of treatment, the overall adverse event (AD) rates were 64% and 74% for dupilumab vs placebo respectively. The most common AEs included nasopharyngitis (8% dupilumab, 9% placebo), upper respiratory tract infection (6% dupilumab, 8% placebo), conjunctivitis (5% dupilumab, 0% placebo), herpes viral infections (6% dupilumab, 5% placebo) and injection site reactions (2% dupilumab, 3% placebo).¹

Detailed results from this trial will be presented at a future meeting, and data will be submitted to regulatory authorities. In 2016, the FDA granted Breakthrough Therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years of age. The efficacy and safety of dupilumab in children below the age of 6 years have not been fully evaluated by any regulatory authority.

Reference:

1. Dupixent® (Dupilumab) pivotal trial meets all primary and secondary endpoints becoming first biologic medicine to significantly reduce signs and symptoms of moderate-to-severe atopic dermatitis in children as young as 6 months. Accessed August 30, 2021. https://www.prnewswire.com/news-releases/dupixent-dupilumab-pivotal-trial-meets-all-primary-and-secondary-endpoints-becoming-first-biologic-medicine-to-significantly-reduce-signs-and-symptoms-of-moderate-to-severe-atopic-dermatitis-in-children-as-young-as-6-months-301364919.html