Dupixent® (dupilumab) is the first biologic to significantly reduce itch and skin lesions in Phase 3 trial for prurigo nodularis, demonstrating the role of type 2 inflammation in this disease
- Pivotal trial met primary and all key secondary endpoints
- Dupixent significantly reduced itch at 12 weeks, and nearly three times as many Dupixent patients experienced reductions in both itch and skin lesions at 24 weeks
- Data reinforce impact of targeting IL-4 and IL-13, key and central drivers of type 2 inflammation, to address itch and skin lesions
- Sixth disease in a Phase 3 trial for Dupixent that reinforces well-established safety profile
PARIS and TARRYTOWN, N.Y. – October 22, 2021 - A pivotal Phase 3 trial evaluating Dupixent® (dupilumab) in adults with uncontrolled prurigo nodularis, a chronic type 2 inflammatory skin disease that causes extreme itch and skin lesions, met its primary and all key secondary endpoints, showing that Dupixent significantly reduced itch and skin lesions compared to placebo in this investigational setting. The impact of uncontrolled prurigo nodularis on quality of life is one of the highest among inflammatory skin diseases with intense, chronic itch.
“We are encouraged that patients in this trial experienced a significant reduction in itch and skin lesions, especially given that prior to enrollment nearly all patients had severe itch and nearly 40% had 100 or more nodules covering their body,” said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. “These data are an important step forward in furthering our knowledge of the role that targeting IL-4 and IL-13 can play in the treatment of skin diseases that cause extreme itch. We are committed to continuing to leverage the robust Dupixent clinical program to transform the understanding of the science behind a number of type 2 inflammatory diseases and look forward to presenting the full results at a future medical congress.”
People with prurigo nodularis experience intense, persistent itch, with thick skin lesions (called nodules) that can cover most of the body. It is often described as painful with burning, stinging and tingling of the skin. The debilitating signs and symptoms of prurigo nodularis can negatively impact health-related quality of life, including mental health, activities of daily living and social interactions. There are no approved systemic treatments for prurigo nodularis. High-potency topical steroids are commonly used, which are associated with safety risks if used long-term.
“Prurigo nodularis is an underdiagnosed disease with immense physical and emotional burden for the 74,000 people in the U.S. who are unable to control their disease with topical steroids and otherwise do not have an approved treatment option,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. “These patients are left to cope with severe itching and painful nodules that, in turn, significantly impair one’s quality of life with many resorting to immunosuppressants and some to antidepressants. These results show – for the first time in a Phase 3 prurigo nodularis trial – that a systemic medicine is able to address the most debilitating symptoms such as itch without broadly suppressing the immune system, building on the promise of Dupixent in a broad range of serious dermatologic, respiratory and gastrointestinal diseases.”
In the Phase 3 PRIME2 trial, topline results comparing Dupixent (n=78) to placebo (n=82) showed:
- 37% of Dupixent patients experienced a clinically meaningful reduction in itch from baseline compared to 22% of placebo patients (p=0.0216) at week 12, the primary endpoint.
- At week 24, nearly three times as many Dupixent patients experienced a clinically meaningful reduction in itch from baseline: 58% of Dupixent patients compared to 20% of placebo patients (p<0.0001).
- At 24 weeks, Dupixent patients were nearly three times as likely to achieve clear or almost clear skin: 45% of Dupixent patients compared to 16% of placebo patients (p<0.0001).
- Dupixent patients experienced significantly greater improvements in measures of health-related quality of life, skin pain and symptoms of anxiety and depression.
The safety results of the trial were generally consistent with the known safety profile of Dupixent in its approved indications. The occurrences of treatment-emergent adverse events were generally similar between Dupixent and placebo groups (57% Dupixent, 51% placebo). The most common adverse events were conjunctivitis (6.5% Dupixent, 0% placebo), herpes viral infections (6.5% Dupixent, 0% placebo) and skin infections (5% Dupixent, 9% placebo). Additionally, 3% of Dupixent patients and 30% of placebo patients discontinued prior to week 24.
An additional trial in the LIBERTY-PN PRIME clinical program, PRIME, is fully enrolled. PRIME has a similar trial design and is expected to read out in the first half of 2022. Sanofi and Regeneron plan to begin regulatory submissions in 2022.
The potential use of Dupixent in prurigo nodularis is currently under clinical development, and the safety and efficacy have not been fully evaluated by any regulatory authority.
About the trial
PRIME2, part of the LIBERTY-PN PRIME clinical program, is a randomized, Phase 3, double-blind, placebo-controlled trial that evaluated the efficacy and safety of Dupixent in 160 adults with prurigo nodularis inadequately controlled with topical prescription therapies or with whom those therapies are not advisable. During the 24-week treatment period, patients received Dupixent or placebo every two weeks with or without topical treatments (low- or medium-dose topical corticosteroids or topical calcineurin inhibitors were continued if patients were using these treatments at randomization).
The primary endpoint evaluated the proportion of patients with clinically meaningful improvement in itch at 12 weeks (measured by a ≥4-point reduction in worst-itch numeric rating scale [WI-NRS] of 0-10). Key secondary endpoints included the proportion of participants with clinically meaningful improvement in itch at 24 weeks and the proportion of participants with clear or almost clear skin at 24 weeks (measured by a score of 0 or 1 on the Investigator's Global Assessment PN-Stage [IGA PN-S] 0-4 scale). Additional secondary endpoints included health-related quality of life (measured by change in baseline according to the 0–30-point Dermatology Life Quality Index), skin pain (measured by change in baseline on a 0-10 scale), and symptoms of anxiety and depression (measured by change in baseline according to a 0-42 Hospital Anxiety and Depression scale).
The average age in the trial was 49 years and 64% were female. Approximately 33% of patients were Asian, 13% were Latino/Hispanic and 5% were Black/African American. In the trial, 46% of patients had at least one coexisting type 2 inflammatory disease. About 24% of patients enrolled had prior history with systemic (non-steroidal) immunosuppressants and 11% had been treated with antidepressants.
Dupixent 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. IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis (CRSwNP).
Dupixent is currently approved in the U.S., Europe, Japan and other countries around the world for use in specific patients with moderate-to-severe atopic dermatitis, as well as certain patients with asthma or CRSwNP in different age populations. Dupixent is also approved in one or more of these indications in more than 60 countries around the world and more than 300,000 patients have been treated globally.
Dupilumab Development Program
To date, dupilumab has been studied across 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.
Sanofi and Regeneron are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes, including chronic obstructive pulmonary disease with evidence of type 2 inflammation (Phase 3), pediatric atopic dermatitis (6 months to 5 years of age, Phase 3), eosinophilic esophagitis (Phase 3), bullous pemphigoid (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), chronic inducible urticaria-cold (Phase 3), chronic rhinosinusitis without nasal polyposis (Phase 3), allergic fungal rhinosinusitis (Phase 3), allergic bronchopulmonary aspergillosis (Phase 3) and peanut allergy (Phase 2). These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority. Dupilumab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement.
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led for over 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
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