Dupixent Meets Endpoints in Phase 2/3 Bullous Pemphigoid Study

Dupixent is the first and only biologic to achieve significant improvements in disease remission and symptoms in bullous pemphigoid positive pivotal study

September 11, 2024

Highlights:

• Study met the primary and all key secondary endpoints in adults with moderate-to-severe disease; five times more patients achieved sustained disease remission with Dupixent than placebo
• Dupixent is the first medicine to show significant steroid-sparing effect in this debilitating and life-threatening disease
• If approved, Dupixent would be the first and only targeted medicine to treat BP in the U.S. and European Union

A Dupixent (dupilumab) pivotal study (ADEPT) in bullous pemphigoid (BP) met the primary and all key secondary endpoints evaluating its investigational use in adults with moderate-to-severe disease. In the study, five times more Dupixent patients achieved sustained disease remission compared to those on placebo. Sustained disease remission was defined as complete clinical remission with completion of oral corticosteroids (OCS) taper by week 16 without relapse and no rescue therapy use during the 36-week treatment period. Dupixent was previously granted Orphan Drug Designation by the U.S. Food and Drug Administration for BP, which applies to investigational medicines intended for the treatment of rare diseases that affect fewer than 200,000 people in the U.S. This study will support regulatory submissions around the world, starting with the U.S. later this year.

“The needs of bullous pemphigoid patients have gone unmet for far too long,” said Patrick Dunn, Executive Director of the International Pemphigus & Pemphigoid Foundation (IPPF). “The IPPF is excited and encouraged by the positive results reported from this study, and we will do everything we can to support future regulatory decisions that will improve the quality of life for people affected by BP. We are grateful for the Sanofi and Regeneron teams, as well as the entire community of patients, caregivers, investigators, researchers, and clinicians who have gotten us to this important milestone.”

BP, a chronic and relapsing disease, is characterized by intense itch and blisters, reddening of the skin, and painful chronic lesions. The blisters and rash can form over much of the body and cause the skin to bleed and crust, resulting in patients being more prone to infection and affecting their daily functioning. “The itchy blisters caused by bullous pemphigoid can be so intense they are debilitating, especially for elderly patients,” said Dietmar Berger, M.D., Ph.D., Chief Medical Officer, Global Head of Development at Sanofi. “There is a significant unmet medical need for new medicines for people suffering with this hard-to-treat disease in which the standard of care is oral and topical corticosteroids and immunosuppressants – treatments that have poor clinical outcomes and safety concerns, respectively, and should be used sparingly in an elderly population. These positive pivotal results for bullous pemphigoid add to an immense body of scientific evidence that underscores the important role IL4 and IL13 play in driving diseases characterized by itch. Combined with the consistent safety profile of the other dermatology indications, these results show the potential of Dupixent to transform the treatment paradigm for bullous pemphigoid.”

“Bullous pemphigoid is a debilitating skin disease with a high mortality rate due to infection,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President, and Chief Scientific Officer at Regeneron. “Dupixent is the first medication to show significant and robust impacts in this patient population. These latest pivotal results reaffirm the underlying role type-2 inflammation plays in driving multiple skin diseases. We look forward to further advancing this research and sharing the positive results from the bullous pemphigoid pivotal trial with regulatory authorities.”

In the ADEPT study, 106 adults with moderate-to-severe BP were randomized to receive Dupixent 300 mg (n=53) every two weeks after an initial loading dose or placebo (n=53), along with standard-of-care OCS. During treatment, all patients underwent a protocol-defined OCS tapering regimen if control of disease activity was maintained.

For the primary endpoint, 20% of Dupixent patients experienced sustained disease remission at 36 weeks compared to 4% for placebo (p=0.0114). For the components comprising the primary endpoint – with patients having to achieve all components – efficacy among patients receiving Dupixent compared to placebo was as follows*:

• Absence of disease relapse after patient completed OCS taper: 59% vs. 16% (nominal p=0.0023)
• Absence of need for rescue therapy during treatment period: 42% vs. 12% (nominal p=0.0004)
• Achievement of complete remission and off OCS by week 16: 38% vs. 27% (not significant)

*Components were not separately included in pre-specified statistical analyses and are therefore nominal

For selected secondary endpoints, results for Dupixent compared to placebo were statistically significant as follows:

• Patients achieving ≥90% reduction in disease severity: 41% vs. 10% (p=0.0003)
• Patients achieving clinically meaningful itch reduction: 40% vs. 11% (p=0.0006)
• Secondary endpoints assessing decreased OCS use, and time to use of rescue medications, also favored Dupixent and were significant (p=0.0220 and p=0.0016, respectively)
• Reduction in disease severity from baseline: 77% vs. 51% (p=0.0021)
• Reduction in itch from baseline: 52% vs. 27% (p=0.0021)
• Days of complete remission off OCS: 40 vs. 13 (p=0.0072)

In this older 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 more than 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.