Sibeprenlimab

Vertex, Novartis and Vor Bio are developing anti-APRIL drugs against IgAN, too. A new FDA approval for a first-in-class drug has vaulted Otsuka into immunoglobulin A nephropathy (IgAN), an increasingly competitive kidney disease field targeted by multiple biopharma companies.The new drug, called Voyxact, has won an FDA accelerated approval to be used to reduce proteinuria in adults with primary IgAN who are at risk of progression, Otsuka said Tuesday.A self-administered injection given once per month, the drug works by blocking A proliferation-inducing ligand (APRIL), a protein that promotes autoantibody production that may trigger inflammation and kidney damage, causing IgAN.The drug, also known as sibeprenlimab, is the first in a growing list of candidates to reach the market targeting this pathway. Other drugmakers, including Vertex, Novartis and Vor Bio are working on anti-APRIL agents against IgAN and other disorders. Voyxact is also the first biologic drug approved for IgAN, whereas all four earlier IgAN FDA approvals went to small molecules.Voyxact won the FDA’s endorsement by proving its ability to reduce proteinuria, or protein in the urine, as measured by the urinary protein-to-creatinine ratio (UPCR). In a phase 3 trial coded Visionary, Voyxact led to a significant placebo-adjusted 51% reduction in proteinuria at nine months of treatment. Patients enrolled in the trial were receiving standard therapies such as ACE inhibitors, angiotensin II receptor blockers and/or SGLT2 inhibitors.After one year of treatment, Voyxact’s placebo-adjusted treatment effect on proteinuria reached 54.3%, according to results presented a few days ago at the American Society of Nephrology Kidney Week 2025 and published in The New England Journal of Medicine.“The availability of Voyxact represents a novel targeted approach to help manage this complex disease for patients living with IgAN,” John Kraus, M.D., Ph.D., chief medical officer of Otsuka, said in a Nov. 25 release. “With its targeted mechanism, strong efficacy, safety profile, and once-every-four-weeks dosing, Voyxact offers a new option for IgAN patients.”Unlike previous accelerated approvals in IgAN, the FDA is not restricting the patient population eligible for Voyxact based on a specific UPCR level. Novartis’ endothelin A receptor antagonist (ERA) Vanrafia, the most recent accelerated approval in IgAN doled out by the FDA in April, is currently allowed for patients with UPCR of at least 1.5 g/g. Travere Therapeutics’ dual ARB/ERA drug Filspari shook off that same UPCR limitation only after winning a full approval last year.To win a traditional nod, Otsuka is on the hook to show whether Voyxact can slow disease progression, as measured by estimated glomerular filtration rate (eGFR) decline, at two years in the ongoing Visionary study. Otsuka said it expects to have that data in early 2026.“We think FDA is comfortable with the eGFR trajectory of this class of drugs to allow broad use,” Jefferies analysts said of Voyxact’s label in a Nov. 25 note.The FDA’s decision here bodes well for future contenders in the APRIL class, the Jefferies team observed.According to Jefferies’ calculations, IgAN represents a large market worth around $6 billion to $10 billion in potential sales per year. But competition within the APRIL class will be intense, the analysts said, and the space is poised to get crowded fast.Several companies are developing BAFF/APRIL duo inhibitors. BAFF, or B-cell activating factor, is another key mediator in the production of abnormal proteins and autoantibodies involved in IgAN.Vera Therapeutics announced on Nov. 7 that it has submitted an FDA application for its BAFF/APRIL med, atacicept, which yielded a 42% reduction in UPCR compared with placebo at nine months at an interim analysis of the phase 3 Origin 3 trial.Through its $4.9 billion acquisition of Alpine Immune Sciences last year, Vertex is preparing an FDA application for an accelerated approval for its BAFF/APRIL drug, povetacicept, in IgAN. The company has said it will begin an FDA rolling submission this year and intends to use a priority review voucher to expedite the regulatory process, potentially leading to a go-ahead by the end of 2026.In the phase 2 Ruby-3 trial, povetacicept elicited absolute proteinuria reductions of 64% at 48 weeks, according to data presented at the recent ASN annual meeting. The trial does not have a placebo control arm.Meanwhile, Vor Bio’s partner RemeGen just reported positive China phase 3 data for its BAFF/APRIL duo inhibitor telitacicept in IgAN, although the drug’s U.S. clinical development plan in the disease remains unclear. What’s more, Novartis has an anti-APRIL drug called zigakibart in addition to FDA-approved Vanrafia and factor B inhibitor Fabhalta, which the company said has shown it can slow kidney function decline and IgAN progression in the final analysis of a phase 3 trial.Otsuka has some experience in the kidney disease space with Jynarque, which was approved by the FDA in 2018 as the first treatment to slow kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD).

The Food and Drug Administration on Tuesday granted accelerated approval to Otsuka Pharmaceutical's injectable medicine, the first in a class of medicines for a rare, potentially life-threatening kidney disease.The new medicine, known as Voyxact, is now approved for its ability to reduce protein in the urine of people with IgA nephropathy, or IgAN, an autoimmune disease that causes protein to build up in the kidneys and that can lead to failure of the organ. Voyxact comes as a self-administered, subcutaneous injection given every four weeks. Otsuka did not disclose pricing.The availability of Voyxact represents a novel targeted approach to help manage this complex disease for patients living with IgAN, said John Kraus, executive vice president and chief medical officer of Otsuka, in a statement.Several therapies exist to treat IgAN. However, because the disease still leads to kidney function decline, demand remains for new treatments. Some estimates hold that up to 130,000 people in the U.S. have the disease, presenting a market opportunity in the range of $6 billion to $10 billion, according to Jefferies analyst Farzin Haque.Such an opportunity has attracted interest from large drugmakers like Vertex Pharmaceuticals, Biogen and Novartis.Otsuka acquired Voyxact, scientifically known as sibeprenlimab, through a 2018 buyout of Visterra. The drug works by blocking a protein called A-proliferation-inducing-ligand, or APRIL, which plays a key role in the development and progression of IgAN.Supporting the approval are interim results from a late-stage study, in which Voyxact reduced proteinuria levels by 51% after nine months compared to a 2% increase in a placebo group. The most common side effects observed were infections and injection site reactions.The study is still ongoing to evaluate a change in kidney function measured by estimated glomerular filtration rate, or eGFR, over 24 months. Data is expected in 2026.Other drugs with the same mechanism may arrive on market in the coming years. Most notably, Voyxact could compete with atacicept, a drug from Vera Therapeutics that targets APRIL as well as a protein called B cell activating factor, or BAFF.In a note to clients, Leerinks Haque argued that Voyxacts labeling bodes well for Vera, as it omits a urine protein/creatinine cutoff, breaking precedent set by four prior accelerated approvals, which would have restricted use to a smaller patient population.Vera submitted the drug to the FDA earlier this month. If approved, it could join enter the market as soon as next year. '