atuzabrutinib (SAR444727) / Sanofi - LARVOL DELTA

Atuzabrutinib Topical Gel Does Not Improve Disease Activity in Patients with Mild-to-Moderate Atopic Dermatitis: Findings from a Phase 2a Trial. (PubMed, J Invest Dermatol) - No abstract available

Journal • P2a data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus

Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2 & PRN473 reduces venous thrombosis formation in mice. (PubMed, Blood Adv) - "Treatment with ibrutinib is associated with increased bleeding due to off-target inhibition of Src family kinases (SFKs). PRN473 significantly reduced the number of thrombi in podoplanin positive vessels following Salmonella infection and the presence of IVC thrombosis following vein stenosis. The potent inhibition of human platelet CLEC-2, and reduced thrombosis in in vivo models, together with the lack of off-target SFK inhibition and absence of bleeding reported in rilzabrutinib treated immune thrombocytopenia patients, suggest Btk inhibition as a promising antithrombotic strategy."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Immunology • Infectious Disease • Primary Immunodeficiency • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis • Venous Thromboembolism • PDPN

Phase 2a Study of the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis (clinicaltrials.gov) - P2 | N=39 | Completed | Sponsor: Principia Biopharma, a Sanofi Company | Phase classification: P2a ➔ P2

Phase classification • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CRP

Phase 2a Study of the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis (clinicaltrials.gov) - P2a | N=38 | Completed | Sponsor: Principia Biopharma, a Sanofi Company | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Phase 2a Study of the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis (clinicaltrials.gov) - P2a | N=38 | Active, not recruiting | Sponsor: Principia Biopharma, a Sanofi Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

What's New in Topicals for Atopic Dermatitis? (PubMed, Am J Clin Dermatol) - "First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and, more recently, the phosphodiesterase inhibitor crisaborole...This review summarizes selected therapeutic topical agents in later phases of development that target various aspects in the pathogenesis of AD such as Janus kinase inhibition (ruxolitinib and delgocitinib), phosphodiesterase-4 inhibition (roflumilast and difamilast), aryl hydrocarbon modulation (tapinarof), and modulation of the microbiome. We also review novel targeted therapies that are in early phase clinical trials, including AMTX-100, BEN-2293, and PRN473. Preliminary findings on efficacy and tolerability of most of these agents are promising, but further studies are warranted to evaluate the long-term safety and efficacy of these novel agents against the current standard of care."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Phase 2a Study of the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis (clinicaltrials.gov) - P2a | N=40 | Recruiting | Sponsor: Principia Biopharma, a Sanofi Company | Trial completion date: Aug 2022 ➔ Feb 2023 | Trial primary completion date: Aug 2022 ➔ Feb 2023

Trial completion date • Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Translational autoimmunity in pemphigus and the role of novel Bruton tyrosine kinase inhibitors. (PubMed, J Transl Autoimmun) - "Assorted clinical trials are underway to assess the safety, tolerability, and pharmacokinetics of distinct BTK inhibitors, including PRN473 and remibrutinib. The current review evaluates translational autoimmunity in pemphigus and discusses BTK inhibitors in the treatment of pemphigus."

Journal • Review • Dermatology • Immunology • Pemphigus Vulgaris

Discovery of Reversible Covalent Bruton's Tyrosine Kinase Inhibitors PRN473 and PRN1008 (Rilzabrutinib). (PubMed, J Med Chem) - "These compounds have exhibited potent and durable inhibition of BTK, in vivo efficacy in rodent arthritis models, and clinical efficacy in canine pemphigus foliaceus. Compound 11 has completed phase 1 trials as a topical agent, and 12 is in phase 3 trials for pemphigus vulgaris and immune thrombocytopenia."

Journal • Dermatology • Hematological Disorders • Immunology • Oncology • Pemphigus Vulgaris • Rheumatology • Thrombocytopenia • Thrombocytopenic Purpura

Sanofi : Strong Q3 performance drives guidance upgrade to around 14% business EPS growth at CER(1) (GlobeNewswire) - "Dupixent® met its primary and all key secondary endpoints in Study A (the first of two trials) of the pivotal LIBERTY CUPID clinical program....in patients with moderate-to-severe chronic spontaneous urticaria (CSU)....This study is expected to read out in H1 2022....SAR444727 (formerly known as PRN473)...entered Phase 2a study, evaluating safety, tolerability, and pharmacokinetics in patients with mild-to-moderate atopic dermatitis..."

P3 data • Trial status • Atopic Dermatitis • Chronic Spontaneous Urticaria • Dermatology • Immunology

Phase 2a Study of the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis (clinicaltrials.gov) - P2a; N=40; Recruiting; Sponsor: Principia Biopharma, a Sanofi Company; Not yet recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Phase 2a Study of the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis (clinicaltrials.gov) - P2a; N=40; Not yet recruiting; Sponsor: Principia Biopharma, a Sanofi Company

New P2a trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Preclinical Mechanisms of Topical PRN473, a Bruton Tyrosine Kinase Inhibitor, in Immune-Mediated Skin Disease Models. (PubMed, Immunohorizons) - "These preclinical studies provide a strong biologic basis for targeting innate immune cell responses locally in the skin, with rapid onset of action following once-daily topical PRN473 administration and minimal systemic exposure. Dose-dependent inhibition in these preclinical models of immune-mediated skin diseases support future clinical studies."

Journal • Preclinical • Dermatology • Inflammation • Pemphigus Vulgaris

[VIRTUAL] Mechanisms of topical Bruton tyrosine kinase inhibitor PRN473 in immune-mediated models of skin disease (EADV 2020) - No abstract available

Dermatology