New deal aims to develop, market povetacicept for AAV in Asia
Vertex, Ono sign agreement for Japan, South Korea on B-cell-targeting therapy
Vertex Pharmaceuticals has signed a license agreement with Ono Pharmaceutical to develop and market povetacicept — a B-cell-targeting candidate for treating ANCA-associated vasculitis (AAV) and other autoimmune diseases driven by self-reactive antibodies and marked by signs or symptoms of kidney involvement — in Japan and South Korea.
Under the agreement, Ono will support the clinical development of povetacicept and file for regulatory approval in the two Asian countries. If approved, Ono will also market the treatment in both nations. In return, Vertex will receive an upfront payment and additional milestone-based payments, as well as royalties on potential future sales. No details on the financial arrangements were provided by the company.
“Ono is a proven leader in Japan and South Korea, bringing established local relationships, infrastructure and [kidney] expertise that make them a perfect partner for Vertex as we look to deliver povetacicept to the thousands of potential patients in these countries,” Reshma Kewalramani, MD, CEO and president of Vertex, said in a company press release.
The agreement covers the use of povetacicept for immunoglobulin A nephropathy (IgAN) and primary membranous nephropathy (pMN) — two diseases where B-cells produce immune complexes or self-reactive antibodies that damage the kidneys’ filtering units, known as glomerulonephritis — with the option to include additional indications later.
“We look forward to collaborating with Vertex to provide this new therapeutic option for patients with IgAN and other autoimmune diseases in Japan and South Korea, and to maximize the value of this treatment,” said Toichi Takino, representative director, president, and chief operating officer at Ono.
Immune B-cells normally produce antibodies that help the body fight infections. In AAV and other autoimmune diseases, some antibodies mistakenly attack the body’s own tissues instead, driving a lasting autoimmune response. This often damages the kidneys.
Originally developed by Alpine Immune Sciences and later acquired by Vertex, povetacicept is designed to block two targets simultaneously for a potentially enhanced therapeutic effect. Its targets are BAFF and APRIL, proteins that help B-cells survive and multiply. Blocking them is expected to reduce the production of disease-causing antibodies, easing symptoms.
Povetacicept now being tested in 2 clinical trials
Povetacicept is now being tested in RUBY-3 (NCT05732402), an open-label Phase 1/2 clinical study that has enrolled 72 adults with a “biopsy-confirmed autoantibody-associated glomerular disease.” Eligible diagnoses include AAV with kidney involvement, IgAN, pMN, and lupus nephritis — an inflammation of the kidneys that occurs as a complication of lupus, also an autoimmune disease.
The ongoing study is looking at the safety of povetacicept and how well it works to treat kidney disease when given as a subcutaneous, or under-the-skin, injection at a dose of 80 or 240 mg every four weeks for six months. Participants have the option to continue treatment for six more months and, if eligible, for an additional year.
Data from 12 adults with IgAN showed that multiple 80 mg doses of povetacicept over six months were well tolerated and more than halved a measure of damage to the kidneys known as the protein-to-creatinine ratio in urine. Treatment also stabilized estimated glomerular filtration rate, which normally declines as the kidneys stop functioning properly.
We are very pleased to partner with Ono and look forward to close collaboration as we continue to advance this potentially best-in-class treatment for … serious B cell-mediated diseases.
Another Phase 3 clinical study, dubbed RAINIER (NCT06564142) and launched last year, is testing 80 mg doses of povetacicept against a placebo in as many as 480 adults with IgAN. An interim analysis will compare the protein-to-creatinine ratio in urine after 36 weeks, or about eight months. If the results are positive, Vertex may seek accelerated U.S. approval for the therapy candidate. The final analysis, after two years, will focus on the decline in estimated glomerular filtration rate.
“We are very pleased to partner with Ono and look forward to close collaboration as we continue to advance this potentially best-in-class treatment for IgAN, pMN and other serious B cell-mediated diseases,” Kewalramani said. The company also is testing povetacicept for autoimmune cytopenias, or low numbers of blood cells.
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