Dupixent Approved in Japan as the First Targeted Therapy for Adults with Bullous Pemphigoid
Regeneron Pharmaceuticals and Sanofi have announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted approval for Dupixent as a treatment for adults suffering from moderate-to-severe Bullous Pemphigoid (BP). This regulatory milestone marks a significant advancement for patients in Japan living with this rare and often debilitating dermatological condition, for which treatment options have historically been limited and associated with considerable safety concerns.
The approval is supported by robust clinical evidence from the pivotal LIBERTY-BP-ADEPT Phase 2/3 clinical trial, a randomized, placebo-controlled study designed to evaluate the efficacy and safety of Dupixent in adult patients diagnosed with moderate-to-severe BP. In the study, a total of 106 participants were enrolled and evenly randomized to receive either Dupixent 300 mg or a placebo, both administered alongside standard-of-care oral corticosteroids (OCS). Importantly, all patients followed a structured corticosteroid tapering protocol during the study period, contingent upon achieving and maintaining disease control. This aspect of the trial reflects a clinically meaningful objective, as long-term corticosteroid use is associated with substantial side effects, particularly in elderly populations who are most commonly affected by BP.
Results from the study demonstrated that Dupixent delivered a statistically significant and clinically meaningful improvement in disease outcomes compared to placebo. By Week 36, 18% of patients treated with Dupixent achieved sustained disease remission, compared to only 4% of patients in the placebo group. This represents more than a fourfold increase in remission rates, with a p-value of 0.0250, indicating statistical significance. Sustained remission is a critical endpoint in BP management, as the disease is characterized by chronic relapses and progressive worsening if not adequately controlled.
In addition to efficacy, the safety profile of Dupixent observed in the trial was generally consistent with previous studies across its approved indications. Treatment-related adverse events were reported in 26% of patients receiving Dupixent, compared to 15% in the placebo arm. The most frequently observed treatment-related adverse event associated with Dupixent was conjunctivitis, reported in 4% of patients. While the incidence of adverse events was higher in the treatment group, the overall safety findings were considered manageable and aligned with the known safety profile of the drug.
The approval of Dupixent for BP in Japan further expands the therapeutic reach of this biologic, which has already established itself as a versatile treatment across a range of type 2 inflammatory diseases. In Japan, Dupixent is currently approved for use in selected patients with conditions including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), prurigo nodularis, chronic spontaneous urticaria (CSU), and chronic obstructive pulmonary disease (COPD). This growing list of indications underscores the role of Dupixent as a targeted therapy addressing the underlying mechanisms of type 2 inflammation, rather than simply alleviating symptoms.
Bullous pemphigoid is a rare autoimmune skin disorder that predominantly affects elderly individuals. It is characterized by severe itching, the formation of large, fluid-filled blisters, and widespread skin inflammation. These symptoms can lead to significant discomfort, pain, and impairment in daily activities. In severe cases, the breakdown of the skin barrier can increase susceptibility to infections, further complicating disease management. The chronic and relapsing nature of BP means that patients often require long-term treatment, which can contribute to cumulative toxicity, particularly when systemic immunosuppressants such as corticosteroids are used.
Current standard treatments for BP largely rely on systemic corticosteroids and immunosuppressive agents. While these therapies can be effective in controlling symptoms, they are associated with a range of adverse effects, including increased risk of infections, metabolic disturbances, and other complications—risks that are particularly concerning in older patients. As such, there is a pressing need for targeted therapies that can provide effective disease control while minimizing systemic toxicity.
Dupixent, a fully human monoclonal antibody, works by inhibiting key drivers of type 2 inflammation, specifically interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling pathways. By targeting these cytokines, Dupixent helps to reduce the inflammatory processes that contribute to the development and progression of BP. Its mechanism of action represents a shift toward precision medicine in dermatology, offering a more targeted approach compared to traditional immunosuppressive therapies.
The approval of Dupixent for BP in Japan represents an important step forward in addressing the unmet medical needs of patients with this challenging condition. It not only provides a new treatment option but also highlights the continued evolution of biologic therapies in the management of autoimmune and inflammatory diseases. For clinicians and patients alike, this development offers renewed hope for improved disease control, reduced reliance on systemic steroids, and enhanced quality of life.
As Regeneron and Sanofi continue to explore the potential of Dupixent across additional indications and patient populations, this latest approval reinforces the drug’s position as a cornerstone therapy in the field of immunology and dermatology.
About ADEPT
ADEPT was a randomized, double-blind, placebo-controlled Phase 2/3 trial 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 after an initial loading dose, along 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 if disease control was maintained, with the intent of completion by Week 16. After OCS tapering, patients were only treated with Dupixent or placebo for the rest of the trial (rescue treatment could be used if required).
The primary endpoint evaluated the proportion of patients achieving sustained disease remission at Week 36. Sustained disease remission was defined as complete clinical remission with completion of OCS taper by Week 16 without relapse after completion of the OCS taper 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) or systemic non-steroidal immunosuppressive medications or immunomodulating biologics.
About Dupixent
Dupixent is now available in Japan as a 300 mg pre-filled syringe or pre-filled pen for adults with bullous pemphigoid. Dupixent is intended for injection under the skin (subcutaneous injection) and is given every two weeks after an initial loading dose. It can be given in a clinic or at home by self-administration after training by a healthcare professional.
Dupixent, which was invented using Regeneron’s proprietary VelocImmune® technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in Phase 3 trials, establishing that IL-4 and IL-13 are two of the key and central drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases.
Dupixent has received regulatory approvals in more than 60 countries in one or more indications including certain patients with atopic dermatitis, asthma, CRSwNP, eosinophilic esophagitis (EoE), prurigo nodularis, CSU, COPD, BP and allergic fungal rhinosinusitis (AFRS) in different age populations. More than 1,400,000 patients are being treated with Dupixent globally.1
About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s co-Founder, Board co-Chair, President and Chief Scientific Officer George D.
Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved fully human monoclonal antibodies.
This includes Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb), Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz® (pozelimab-bbfg). In addition, REGEN-COV® (casirivimab and imdevimab) had been authorized by the FDA during the COVID-19 pandemic until 2024.
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