SOUTH SAN FRANCISCO, CA, USA I September 17, 2020 I Principia Biopharma Inc. (Nasdaq: PRNB), a late-stage biopharmaceutical company focused on developing treatments for immune mediated diseases, today announced that the first patient was dosed in an open label two-arm trial to evaluate rilzabrutinib in IgG4-related disease (RD).
“IgG4-RD is a serious fibro-inflammatory disease that can affect nearly any organ. The disease has long been under-diagnosed and under-treated, so we believe there is a significant medical need to have fast acting steroid free treatments with persistent responses. We believe rilzabrutinib has the potential to lead to positive outcomes in IgG4-RD by impacting many of the driving effector cells of the disease, including inflammatory monocytes, macrophages, eosinophils, B cells, IgG4+ plasmablasts and cytotoxic T-cells,” said Martin Babler, president and chief executive officer of Principia.
About the Phase 2A Trial
This multicenter Phase 2A trial is anticipated to enroll approximately 25 patients with active IgG4-RD in two arms, rilzabrutinib with glucocorticoids or glucocorticoids only. Patients who meet all the inclusion criteria after completion of the four-week screening period will be randomized in a 3:1 ratio to the rilzabrutinib with glucocorticoids arm or the glucocorticoids only arm. The main treatment period is 12 weeks, and patients may then be eligible to enter a treatment extension period of 40 weeks, followed by a four-week safety follow-up period. The primary endpoint of the trial is the proportion of patients who achieve complete remission at week 12 with no glucocorticoid use at Week 4 for the rilzabrutinib arm and week 12 for the glucocorticoids arm.
About IgG4 Related Disease
There is significant need for new treatment options for patients with IgG4-RD. IgG4-RD is an immune-mediated disease of chronic inflammation and fibrosis that, if left untreated, can lead to severe morbidity including organ dysfunction and organ failure, which can be fatal. IgG4-related disease typically manifests with multiple organ involvement including but not limited to exocrine glands, GI tract organs (liver, pancreas), and kidneys.
Treatment is typically glucocorticoids (GCs); however, patients often relapse after GCs are tapered and thus require chronic GC dosing, which can lead to severe and debilitating side effects. Rituximab has been shown to have an effective clinical response; however, patients frequently relapse after treatment as well. Recent advances in the field have led to recognition of this disease and the many unmet needs for the patients diagnosed with it. Awareness and recognition of IgG4-RD is growing, and the exact prevalence remains unknown, with estimates ranging from 40,000 to 180,000 in the United States alone.
About Rilzabrutinib
Rilzabrutinib, Principia’s most advanced drug candidate, is an oral, first-in-class, reversible covalent, Bruton tyrosine kinase (BTK) inhibitor optimized for the treatment of immune mediated diseases. BTK is involved in innate and adaptive immune responses and is a critical signaling molecule in immune mediated diseases. Rilzabrutinib data demonstrates an ability to block inflammatory immune cells, eliminate autoantibody destructive signaling, and prevent new autoantibody production without depleting B cells. Rilzabrutinib’s unique attributes are based in the power of the bond from Principia’s proprietary Tailored Covalency® platform. This enabled the company to optimize rilzabrutinib’s safety and efficacy profile, with prolonged and reversible action at the target site while being rapidly eliminated from the body. Principia believes this bonding and the limited systemic exposure of rilzabrutinib enables rapid clinical reversibility of effects on the immune system, and it is thus designed for safety in immune mediated diseases.
About Principia Biopharma
Principia is a late-stage biopharmaceutical company dedicated to bringing transformative therapies to patients with significant unmet medical needs in immune mediated diseases. Through Principia’s proprietary Tailored Covalency® platform, our strategy is to build and advance a pipeline of best-in-class drug candidates with significant therapeutic benefits, limit unintended side effects, improve quality of life and over time modify the course of disease. This highly reproducible approach enables the company to pursue multiple programs efficiently, having discovered three drug candidates. Rilzabrutinib, a reversible covalent BTK inhibitor, is being evaluated in a global Phase 3 clinical trial in pemphigus, a Phase 1/2 clinical trial in immune thrombocytopenia (ITP), a Phase 2A clinical trial in IgG4-RD and the company plans to initiate a Phase 3 trial in ITP. PRN2246/SAR442168 is a covalent BTK inhibitor which crosses the blood-brain barrier and is licensed to Sanofi. Sanofi has announced that SAR442168 has entered Phase 3 clinical trials in multiple sclerosis. PRN473 Topical, a topical reversible covalent BTK inhibitor designed for immune-mediated diseases that could benefit from localized application to the skin, is being evaluated in Phase 1 trials. For more information, please visit www.principiabio.com.
SOURCE: Principia Biopharma
