Dupixent® (dupilumab) Achieves Positive Results in Two Phase 3 Trials for Prurigo Nodularis, Demonstrating Significant Reduction in Itch and Skin Lesions

Prurigo Nodularis (Image Source: askdrshah.com)

News on January 19, 2022 /BioValleyBIOON/ -- Sanofi and its partner Regeneron recently announced positive results from the second Phase 3 trial evaluating Dupixent (Chinese trade name: 达必妥, generic name: dupilumab) for the treatment of adults with uncontrolled prurigo nodularis.Clinical Trial(PRIME) results.

The trial met its primary endpoint and all key secondary endpoints: Dupixent significantly reduced itching and skin lesions compared to placebo.. Specific data are as follows:At 24 weeks, the proportion of patients in the Dupixent treatment group who experienced a clinically meaningful reduction in itching was more than three times that of the placebo group (60% vs 18%; p<0.0001), and the proportion of patients with clear or almost clear skin was nearly three times that of the placebo group (48% vs 18%; p=0.0004).. These data confirm the positive results of the previously announced Phase 3 PRIME2 trial.

Prurigo Nodularis is a chronic type 2 inflammatory skin disease that causes intense itching and inflammatory skin lesions (nodules). The impact of uncontrolled Prurigo Nodularis on quality of life is one of the most severe among inflammatory skin diseases, accompanied by strong chronic itching. Currently, there are no approved systemic treatments for Prurigo Nodularis. High-potency topical steroids are commonly used in clinical practice, but long-term use poses safety risks.

PRIME is part of the LIBERTY-PN PRIME clinical program, and another trial in this program, PRIME2, has a similar design to PRIME. Topline results were announced in October 2021. Based on the data from this program, Sanofi and Regeneron plan to submit a new indication application for Dupixent in treating prurigo nodularis in 2022.

Regeneron's President and Chief Scientific Officer George D. Yancopoulos, M.D., Ph.D., stated: "Prurigo nodularis is a disease with a heavy burden, involving dozens (even hundreds) of persistent itchy and burning skin lesions, which can lead to complications such as skin infections. The results of the PRIME trial once again demonstrate that Dupixent can significantly address the hallmark symptoms of this disease while maintaining consistent safety, including a numerical reduction in the rate of skin infections. We are encouraged by the progress of the broad Dupixent development program, which continues to reinforce that IL-4 and IL-13 are key drivers of type 2 inflammation in many diseases, including dermatological conditions (such as prurigo nodularis and atopic dermatitis) and respiratory diseases (such asAsthmaand CRSwNP), gastrointestinal diseases (such as eosinophilic esophagitis)."

John Reed, Ph.D., Global Head of Research and Development at Sanofi, said: "These results strengthen our understanding of the fundamental biology of prurigo nodularis and are encouraging as we seek to help patients severely affected by symptoms such as intense itching, skin lesions, tingling, and burning. We firmly believe that type 2 inflammation is a key driver of this highly pruritic disease, leading us to directly accelerate into phase 3 development for prurigo nodularis."Clinical Trial", which demonstrates our commitment to rapidly providing new therapies to patient populations in urgent need of new options."

Mechanism of Action of Dupixent (Image Source: dupixenthcp.com)

PRIME is a randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy and safety of Dupixent in 151 patients with prurigo nodularis whose disease was inadequately controlled with topical prescription therapies or for whom these treatments were not advisable. During the 24-week treatment period, patients received Dupixent (n=75) or placebo (n=76) every two weeks, with or without topical treatments (low- or mid-potency topical corticosteroids or topical calcineurin inhibitors, continued if used by patients at randomization). In this trial, 46% of patients had at least one coexisting type 2 inflammatory disease. Approximately 24% of patients had a history of systemic (non-steroidal) immunosuppressant use, and 11% had been treated with antidepressants.

The primary endpoint assessed the proportion of patients with clinically meaningful improvement in pruritus at Week 24 (measured by a reduction of ≥4 points on the Worst Itch Numeric Rating Scale [WI-NRS] [0-10]). The key secondary endpoint was the proportion of patients with complete or almost complete clearance of skin lesions at Week 24 (measured by an Investigator's Global Assessment for Prurigo Nodularis [IGA PN-S] score of 0 or 1 on a 0-4 scale). Other secondary endpoints included health-related quality of life (measured by the change from baseline in the Dermatology Life Quality Index [DLQI] on a 0-30 scale), skin pain (measured by the change from baseline on a 0-10 scale), and anxiety andDepressionStatus (measured by the change from baseline in the Hospital Anxiety and Depression Scale score, ranging from 0 to 42).

In addition, the Dupixent treatment group showed improvements in health-related quality of life, skin pain, anxiety, andDepressionSignificant improvements in both conditions.The safety results of this trial were consistent with those observed in the PRIME2 trial and were generally consistent with the known safety profile of Dupixent in its approved indications.

Dupixent targets the key drivers of type 2 inflammation. It is a fully human monoclonal antibody that specifically inhibits overactive signaling of two key proteins, IL-4 and IL-13. IL-4 and IL-13 are two cytokines that are considered to be key drivers of intrinsic inflammation in allergic diseases and other type 2 inflammatory diseases, including atopic dermatitis.Asthma, Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), etc.

Dupixent was launched at the end of March 2017 and has currently been approved to treat three diseases caused by type 2 inflammation: moderate to severe atopic dermatitis (patients ≥6 years old), moderate to severeAsthma(≥6 years old patients), chronic rhinosinusitis with nasal polyps (CRSwNP, adult patients).

In China, in June 2020, Dupixent (Dupilumab) was approved by the National Medical Products Administration (NMPA) for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD). Dupixent is the world's first and only targeted biologic therapy approved for treating adult patients with moderate-to-severe atopic dermatitis, addressing an unmet clinical need in China by providing rapid, significant, and sustained improvement in skin lesions and pruritus symptoms in AD patients. Thanks to the regulatory reforms, Dupixent received approval in China two years ahead of schedule, offering Chinese patients a new treatment option.

Currently, Sanofi and Regeneron are also conducting an extensive clinical program to evaluate Dupixent for the treatment of diseases caused by allergies and other type 2 inflammations, including: chronic obstructive pulmonary disease (Phase 3), pediatric atopic dermatitis (6 months to 5 years, Phase 3), eosinophilic esophagitis (Phase 3), bullous pemphigoid (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), chronic inducible urticaria (Phase 3), chronic rhinosinusitis without nasal polyps (Phase 3), allergic fungal rhinosinusitis (Phase 3), allergic bronchopulmonary aspergillosis (Phase 3), and peanut allergy (Phase 2). (Bioon.com)

Source of the original text:Second positive Phase 3 Dupixent® (dupilumab) trial confirms significant improvements for patients with prurigo nodularis