Vertex Pharmaceuticals and Ono Pharmaceutical have announced an exclusive collaboration and license agreement for the development and commercialization of povetacicept in Japan and South Korea, marking a significant strategic expansion for Vertex's nephrology pipeline into key Asian markets.
The partnership centers on povetacicept, a recombinant fusion protein therapeutic and dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines. The investigational therapy is being developed for multiple serious B cell-mediated diseases, including IgA nephropathy (IgAN) and primary membranous nephropathy (pMN).
Addressing Critical Unmet Medical Needs
IgAN represents the most common cause of primary glomerulonephritis, affecting approximately 300,000 people in the United States and Europe, with an estimated 33,000 diagnosed patients in Japan. The disease results from deposition of circulating immune complexes in the renal glomerular mesangium, triggering kidney injury and fibrosis. Up to 72% of adult IgAN patients progress to end-stage renal disease within 20 years, yet there are no approved therapies that specifically target the underlying cause of IgAN.
Primary membranous nephropathy affects approximately 150,000 people in the U.S. and Europe, with an estimated 6,000 diagnosed patients with pMN in Japan. This rare glomerular disease occurs when the body generates an abnormal immune response, including autoantibodies, against kidney proteins, leading to progressive loss of kidney function. Like IgAN, there are no approved therapies that specifically target the underlying cause of pMN.
Strategic Partnership Terms
Under the agreement terms, Ono will pay Vertex an upfront payment, along with certain regulatory and commercial milestone payments and tiered royalties. Ono will utilize its extensive development expertise to help advance Vertex's clinical trials for povetacicept and will be responsible for obtaining marketing authorizations in Japan and South Korea. Following approval, Ono will be solely responsible for commercializing povetacicept in these regions.
"Vertex has a strong track record of developing innovative therapies for serious diseases. Through this strategic partnership, we can strengthen our late-stage pipeline in the immunology field, which is a key focus area for Ono," said Toichi Takino, Representative Director, President and Chief Operating Officer of Ono.
Clinical Development Program
Povetacicept is currently being evaluated in the RAINIER Phase 3 pivotal trial, a global study of povetacicept 80 mg versus placebo on top of standard of care in approximately 480 people with IgAN. The study includes 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.
The Phase 3 clinical trial is underway in multiple regions, including the U.S., EU and Asia. Japanese and South Korean regulatory authorities have approved the Clinical Trial Application (CTA) for RAINIER, where the Phase 3 trial is currently underway.
Additionally, the RUBY-3 study is an ongoing, multiple ascending dose, multi-cohort, open label, Phase 1/2 basket study of povetacicept in autoimmune glomerulonephritis, including IgAN, primary membranous nephropathy, lupus nephritis, and ANCA-associated vasculitis with glomerulonephritis.
Therapeutic Mechanism and Potential
Based upon an engineered TACI (transmembrane activator and calcium modulator ligand interactor) domain, povetacicept has demonstrated higher binding affinity and greater potency in preclinical studies versus other inhibitors of BAFF and/or APRIL alone. The therapy has shown potential best-in-class efficacy in clinical trials in patients with IgA nephropathy and primary membranous nephropathy.
"Ono is a proven leader in Japan and South Korea, bringing established local relationships, infrastructure, and nephrology expertise that make them a perfect partner for Vertex as we look to deliver povetacicept to the thousands of potential patients in these countries," said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex.
The collaboration includes povetacicept for both IgAN and pMN, with the potential to add other indications as the companies continue to explore the therapeutic's application across multiple serious B cell-mediated diseases.
