Zai Lab and Vertex Pharmaceuticals Team Up for Povetacicept: A Promising Therapy for IgA Nephropathy
Saturday, Jan 11, 2025 7:51 am ET
Zai Lab Limited (ZLAB) and Vertex Pharmaceuticals Incorporated (VRTX) have announced an exclusive collaboration and licensing agreement for the development and commercialization of Vertex's povetacicept in mainland China, Hong Kong SAR, Macau SAR, Taiwan region, and Singapore. This strategic partnership aims to bring a potential best-in-class therapy for Immunoglobulin A nephropathy (IgAN) and other B cell-mediated diseases to patients in need.
Povetacicept is a recombinant fusion protein therapeutic and a dual antagonist of BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand), which play key roles in the pathogenesis of multiple autoimmune diseases. Based on an engineered TACI (transmembrane activator and CAML interactor) domain, povetacicept has higher binding affinity and greater potency in preclinical studies compared to other inhibitors of BAFF and/or APRIL alone. It has demonstrated potential best-in-class efficacy in clinical trials for IgA nephropathy and primary membranous nephropathy.
Under the terms of the agreement, Vertex will receive an upfront payment, regulatory milestone payments, and tiered royalties on net sales of povetacicept in the licensed territories. Zai Lab will leverage its extensive research and development expertise to help advance clinical trials and make regulatory submissions in the licensed territory. Leveraging its large commercial footprint, Zai Lab will be responsible for all commercialization activities in the licensed territory once povetacicept becomes an approved product.
IgAN is a serious, progressive, life-threatening, B cell-mediated chronic kidney disease that is the most common cause of primary (idiopathic) glomerulonephritis, affecting approximately 300,000 people in the United States and Europe. It is estimated that there are three to five million patients with IgAN in China, including approximately 750,000 people who are already diagnosed with the disease. IgAN results from deposition of circulating immune complexes consisting of immunoglobulins and galactose-deficient immunoglobulin A (Gd-IgA1) in the renal glomerular mesangium, triggering kidney injury and fibrosis. A high percentage of people with IgAN progress to end-stage renal disease. There are no approved therapies that specifically target the underlying cause of IgAN.
The RAINIER trial is a global Phase 3 pivotal trial of povetacicept 80 mg vs. placebo on top of standard of care in approximately 480 people with IgAN. The study is designed to have a pre-planned interim analysis evaluating urine protein to creatinine ratio (UPCR) for the povetacicept arm versus placebo after a certain number of patients reach 36 weeks of treatment. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval in the U.S. Final analysis will occur at two years of treatment, with a primary endpoint of total eGFR slope through Week 104.
The RUBY-3 trial is an ongoing, multiple ascending dose, multi-cohort, open-label, Phase 1b/2a study evaluating the safety, tolerability, and pharmacokinetics of povetacicept in healthy volunteers and patients with IgAN. The trial is designed to assess the dose-response relationship, identify the maximum tolerated dose, and evaluate the safety and pharmacokinetics of povetacicept in patients with IgAN.
The collaboration between Zai Lab and Vertex Pharmaceuticals is a significant development in the biopharmaceutical landscape, particularly in the Asian market. The focus on povetacicept, a dual antagonist with best-in-class potential, addresses a critical unmet need in treating IgAN and other B cell-mediated diseases. With a large patient population in China and surrounding regions, the market potential is substantial. This partnership not only strengthens Zai Lab's position in immunology but also enhances Vertex's global footprint.
