Sanofi's First-in-Class Oral Reversible BTK Inhibitor Rilzabrutinib Fails Phase 3 Trial in Pemphigus

September 9, 2021 News /BioonBIOON/ --Sanofi recently announced,The Phase 3 PEGASUS study evaluating rilzabrutinib for the treatment of pemphigus did not meet its primary and key secondary endpoints.。In this study, the safety profile of rilzabrutinib was consistent with previous results, and no new safety signals were identified. Pemphigus is a rareAutoimmunitydisease, characterized by vesicles and ulcers on the skin and mucous membranes.

rilzabrutinib is a potential first-in-class oral Bruton's tyrosine kinase (BTK) inhibitor., incorporating Sanofi's TAILORED COVALENCY® technology, is currently being developed for the treatment of immune-mediated diseases. BTK is an intracellular signaling molecule involved in the innate and adaptive immune responses associated with certain immune-mediated diseases. By inhibiting BTK, rilzabrutinib has the potential to target the underlying disease pathogenesis. Previously, in the United StatesFDARilzabrutinib has been granted Orphan Drug Designation (ODD) and Fast Track Designation (FTD) for the treatment of pemphigus vulgaris and immune thrombocytopenia (ITP). In the European Union, rilzabrutinib has been granted Orphan Drug Designation for the treatment of pemphigus.

Notably,The Phase 3 PEGASUS study is the first placebo-controlled study of a BTK inhibitor for the treatment of pemphigus., the enrolled patients were adults with moderate to severe pemphigus vulgaris or pemphigus foliaceus. The primary endpoint was complete remission with a minimal corticosteroid dose (≤10 mg/day) between weeks 29 and 37. Complete remission was defined as the absence of new and pre-existing skin lesions. The results showed that,There was no significant difference in the proportion of patients achieving the primary endpoint between the rilzabrutinib treatment group and the placebo group.Currently, Sanofi is continuing to evaluate the data and plans to at future medicalMeetingShare detailed results above.

Sanofi Global Development、ImmunologyHead of Immunology and Inflammation Naimish Patel stated: "While these results are disappointing, we believe the rilzabrutinib clinical program holds significant potential in addressing the unmet treatment needs of patients with immune-mediated diseases. Our mission is to elevate the standard of care and improve treatment outcomes by exploring novel scientific approaches and new therapies. We remain committed to further investigating rilzabrutinib and advancing our clinical program to provide new treatment options for patients."

Chemical structure of rilzabrutinib (Image source: PubChem)

Pemphigus is a group of potentially life-threatening disorders characterized by blisters and ulcers on the skin and mucous membranes. Currently, treatment options for pemphigus (including pemphigus vulgaris and pemphigus foliaceus) are limited, and systemic corticosteroid therapy remains the standard of care.

Rilzabrutinib is a potential first-in-class, reversible covalent, oral Bruton's tyrosine kinase (BTK) inhibitor for the treatment of immune-mediated diseases. The BTK enzyme plays a critical role in various immune processes, including B cell proliferation, immunoglobulin production, and the activation of innate immune cells (such as mast cells, eosinophils, and basophils).

Positive Results from Placebo-Controlled Studies of BTK InhibitorsClinical TrialData show that BTK in the classRheumatic Arthritisand demonstrates potential therapeutic efficacy in chronic spontaneous urticaria. Therefore, the diverse biological functions of BTK support continued research into a range of serious diseases involving BTK that represent significant unmet medical needs.

Currently, rilzabrutinib is being evaluated in a Phase 3 clinical trial for the treatment of the rare blood disorder immune thrombocytopenia (ITP), in Phase 2Clinical TrialInterim Treatment AssessmentAutoimmunityIgG4-Related Disease. Rilzabrutinib TreatmentAsthma、atopic dermatitis, chronic spontaneous urticaria, and heat-inducedAutoimmunityhemolyticAnemiaAdditional Phase 2 studies for immune-mediated diseases, including previously mentioned indications, are expected to be initiated in 2021. (Bioon.com)

Original Source:Sanofi provides update on Phase 3 study evaluating rilzabrutinib for the treatment of pemphigus