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Positive results of the Phase III PRIME trial evaluating Sanifi’s Dupilumap in adults with unresectable prurigo nodular were recently presented at the 2022 European Academy of Dermatology and Venereology (EADV) Congress.
These data from one of two major prurigo nodularis trials show that the drug significantly reduced itching and skin lesions at 24 weeks. In total, 22 scientific abstracts are presented in the EADV analyzing dupilumab in atopic dermatitis in patients less than 6 months of age and its potential use in chronic spontaneous urticaria and bullous pemphigoid, as well as nodular prurigo .
Gil Yosipovich, professor of dermatology at the University of Miami Miller School of Medicine, director of the Miami Itch Center and principal investigator of the trial, says, “These positive results from the second of two phase III trials with dupilumab in prurigo nodularis confirm that IL-4 may be used to treat IL-4. And inhibition of IL-13 can reduce the persistent itching and widespread severe skin lesions that often affect the patient’s quality of life. In my practice, itch relief and skin lightening of the lesioned skin are often associated with my patients. These data suggest that dupilumab has the potential to address and treat these debilitating symptoms in other type 2 chronic skin diseases with underlying inflammation.”
The late-breaking data presented at EADV 2022 are from the randomized Phase III PRIME trial with a placebo-controlled arm, which meets the major primary and secondary endpoints. At 24 weeks in Dupixent-treated patients in the trial:
• The primary endpoint of the trial, the primary endpoint of the trial, experienced a clinically significant reduction in itching from baseline by more than three-fold (60%) compared to patients treated with placebo (18%; P<0.0001).
Nearly three times (48%) achieved clear or almost clear lesioned skin, a secondary endpoint of the trial, compared with placebo-treated patients (18%; p=0.0004).
The safety results were generally consistent with the known safety profile of the drug in its approved dermatological indication. For the 24-week treatment period, the overall adverse event (AE) rate was 71% for treatment and 63% for placebo. The most frequently observed AEs with study drug (≥5%) were nasopharyngitis (5% dupilumab, 4% placebo) and 1/5 headache (5% drug, 5% placebo). The treatment discontinuation rate due to AEs before 24 weeks was 0% with dupilumab, compared to 4% with placebo. Numerically lower rates of skin infections were observed with Dupixent (4% drug, 9% placebo).
Its results and the first phase III trial, PRIME2, will form the basis for the worldwide application of dupilumab for prurigo nodularis this year. The European Commission and the FDA (US Food and Drug Administration) are already reviewing regulatory applications, with the FDA providing a priority review in May 2022 with development expected by September 30, 2020. 2022.
The potential use of dupilumab in prurigo nodularis, chronic spontaneous urticaria, and bullous pemphigoid is currently in clinical development, and no regulatory authority has fully evaluated its safety and efficacy.
Patients with prurigo nodularis experience intense and persistent itching, accompanied by thick skin lesions (called nodules) that can cover most of the body. Prurigo nodularis is often described as painful with burning, stinging and tingling in the skin.
The impact of undiagnosed prurigo nodularis on quality of life is greatest among inflammatory skin diseases characterized by excessive itching and compared to other debilitating chronic diseases that can negatively affect mental health, activities of daily living and social interactions . High-potency topical corticosteroids are often prescribed but are associated with safety risks when used over a long period of time.
PRIME, part of the LIBERTY-PN PRIME Clinical Program, is a phase III, randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of dupilumab in 151 adults with uncontrolled prurigo nodularis. These included patients who were not adequately controlled with topical treatments or for whom those treatments were not appropriate.
During the 24-week treatment period, patients received Dupixent or placebo every other week, with or without topical treatment (low-dose or medium-dose topical corticosteroids or topical calcineurin if patients were using these treatments in randomization blockade was continued).
The primary endpoint of the trial was to assess the proportion of patients with clinically significant improvement in itching at 24 weeks (measured by a reduction of ≥4 points on the worst itching numerical rating scale). [Worst-Itch Numeric Rating Scale, WI-NRS] from 0 to 10).
A secondary endpoint was the proportion of patients with clear or almost clear skin lesions at 24 weeks (measured by a score of 0 or 1 on a 0 to 4 scale of investigator’s global assessment of PN stage). [IGA PN-S]) Dupixent is a fully human monoclonal antibody that inhibits the interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling pathways.
It is not an immunosuppressant. The drug development program has demonstrated significant clinical benefit and decreased type 2 inflammation in phase III trials, establishing that IL-4 and IL-13 are major and central drivers of type 2 inflammation. 2 which plays an important role in many related and often comorbid diseases.
These conditions include the approved indications of dupilumab for investigational conditions such as asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyposis (CRPNS), and eosinophilic esophagitis (EoE) as well as prurigo nodularis.
Dupilumab has received worldwide regulatory approval for use in selected patients with atopic dermatitis, asthma, CRSCPN, or EoE in various age populations. It is currently approved for these indications in the US and for one or more of these indications in more than 60 countries, including the European Union and Japan. More than 500,000 patients have been treated with this drug worldwide.
In Spain, it is marketed for severe atopic dermatitis in adults, adolescents, and children 6 years of age; As well as for severe asthma with type 2 inflammation in adults and adolescents 12 years of age and older.
Dupilumab is being developed jointly by Sanofi and Regeneron under a global collaboration agreement. To date, it has been studied in over 10,000 patients in 60 clinical trials in various chronic diseases based on type 2 inflammation.
In addition to the currently accepted indications, Sanofi and Regeneron are studying dupilumab in a wide range of diseases resulting from type 2 inflammatory or other allergic processes, including prurigo nodular, pediatric eosinophilic esophagitis, atopic dermatitis of the hands and feet. Includes inflammatory, chronic spontaneous urticaria. Cold-inducing urticaria, chronic pruritus of unknown origin, chronic obstructive pulmonary disease with evidence of inflammatory type 2, chronic rhinosinusitis without nasal polyposis, allergic fungal rhinosinusitis, allergic bronchopulmonary aspergillosis, and bullous pemphigoid.
These potential uses of dupilumab are currently under clinical investigation, and safety and efficacy in these situations have not been fully evaluated by any regulatory authority. These potential uses are currently under investigation and no health authority has fully evaluated its safety and effectiveness in these conditions.