Dupixent Shows Positive Data at AAD

BP is a chronic, debilitating, and relapsing skin disease with underlying type 2 inflammation and characterized by intense itch and blisters, reddening of the skin, and painful lesions.

Victoria Werth, MD, Chief of the Division of Dermatology at the Philadelphia Veterans Administration Hospital, Professor of Dermatology and Medicine at the Hospital of the University of Pennsylvania and the Veteran's Administration Medical Center, and principal investigator of the study: “People with bullous pemphigoid live with unrelenting itch, blisters, and painful lesions that can be debilitating and make it difficult to function daily. Moreover, current treatment options can be challenging for this primarily elderly patient population because they work by suppressing their immune system. By targeting the underlying type 2 inflammation, which is a key driver for bullous pemphigoid, Dupixent is the first investigational biologic to show sustained disease remission and reduce disease severity and itch compared to placebo in a clinical study.”

The ADEPT study met all primary and key secondary endpoints, enrolling 106 adults with moderate-to-severe BP who were randomized to receive Dupixent 300 mg (n=53) every two weeks after an initial loading dose or placebo (n=53) added to standard-of-care oral corticosteroids (OCS). During treatment, all patients underwent a protocol-defined OCS tapering regimen if control of disease activity was maintained. Sustained disease remission was defined as complete clinical remission with completion of OCS taper by week 16 without relapse and no rescue therapy use during the 36-week treatment period.

As presented at AAD, results for Dupixent-treated patients at 36 weeks, compared to those treated with placebo, were as follows:

i)  20% experienced sustained disease remission, the primary endpoint, compared to 4% (p=0.0114)

ii) 40% achieved ≥90% reduction in disease severity compared to 10% (p=0.0003)

iii) 40% achieved clinically meaningful itch reduction compared to 11% (p=0.0006)

iv) 1678 mg reduction in cumulative OCS exposure (p=0.0220) on average and a 54% lower risk of rescue medication use (p=0.0016)

In this elderly population, overall rates of adverse events (AEs) were 96% (n=51) for Dupixent and 96% (n=51) for placebo. AEs more commonly observed with Dupixent compared to placebo in at least 3 patients included peripheral edema (n=8 vs. n=5), arthralgia (n=5 vs. n=3), back pain (n=4 vs. n=2), blurred vision (n=4 vs. n=0), hypertension (n=4 vs. n=3), asthma (n=4 vs. n=1), conjunctivitis (n=4 vs. n=0), constipation (n=4 vs. n=1), upper respiratory tract infection (n=3 vs. n=1), limb injury (n=3 vs. n=2), and insomnia (n=3 vs. n=2). There were no AEs leading to death in the Dupixent group and 2 AEs leading to death in the placebo group.

In February, the FDA accepted for priority review the supplemental biologics license application for Dupixent to treat BP. The FDA decision is expected by June 20, 2025. Dupixent was previously granted orphan drug designation by the FDA for BP, which applies to investigational medicines intended for the treatment of rare diseases that affect fewer than 200,000 people in the US. Additional applications are also under review around the world, including in the EU.

About the Dupixent BP pivotal study: ADEPT is a randomized, phase II/III, double-blind, placebo-controlled study evaluating the efficacy and safety of Dupixent in 106 adults with moderate-to-severe BP for a 52-week treatment period. After randomization, patients received Dupixent or placebo every two weeks, with OCS treatment. During treatment, OCS taper was initiated after patients experienced two weeks of sustained control of disease activity. OCS tapering could start between four to six weeks after randomization and was continued as long as disease control was maintained, with the intent of completion by 16 weeks. After OCS tapering, patients were only treated with Dupixent or placebo for at least 20 weeks, unless rescue treatment was required.

The primary endpoint evaluated the proportion of patients achieving sustained disease remission at 36 weeks. Sustained disease remission was defined as complete clinical remission with completion of OCS taper by 16 weeks without relapse and no rescue therapy use during the 36-week treatment period. Relapse was defined as appearance of ≥3 new lesions a month or ≥1 large lesion or urticarial plaque (>10 cm in diameter) that did not heal within a week. Rescue therapy could include treatment with high-potency topical corticosteroids, OCS (including increase of OCS dose during the taper or re-initiation of OCS after completion of the OCS taper), systemic non-steroidal immunosuppressive medications, or immunomodulating biologics.

Select secondary endpoints evaluated at 36 weeks included: i) proportion of patients achieving ≥90% reduction in Bullous Pemphigoid Disease Area Index (scale: 0-360); ii) Proportion of patients with ≥4-point reduction in Peak Pruritus Numerical Rating Scale (scale 0-10) score; iii) Total cumulative OCS dose; iv) Time to first use of rescue medication.