When Vera Therapeutics in-licensed atacicept from Merck KGaA about six years ago, patients with IgA nephropathy (IgAN) had no FDA-approved treatment options. Today, the dual-target drug has crossed the regulatory finish line but is entering a vastly different landscape as the sixth drug approved for the rare kidney disease.
Atacicept, a recombinant fusion protein to be marketed under the brand name Trutakna, is now the first drug in the U.S. that inhibits both B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL), two cytokines involved in B-cell survival and the production of autoantibodies associated with IgAN.
The FDA doled out its first IgAN approval to Calliditas Therapeutics’ corticosteroid Tarpeyo in 2021. Since then, the agency has cleared a dual endothelin angiotensin receptor antagonist in Travere Therapeutics’ Filspari, plus Novartis’ endothelin A receptor blocker Vanrafia and complement inhibitor Fabhalta. Otsuka’s Voyxact, which targets APRIL alone, reached the market toward the end of 2025.
“Mechanistically, there are multiple places in IgAN pathogenesis to intervene, and Vera’s approach has been to intervene as far upstream as possible,” Marshall Fordyce, M.D., founder and CEO of Vera, said in an interview with Fierce Pharma ahead of the approval.
IgAN is a progressive autoimmune disease of the kidney. As IgA antibodies build up, the kidneys gradually lose their ability to filter waste, causing protein to spill into the urine.
As it did with Otsuka’s Voyxact, the FDA does not restrict who may be eligible for Vera’s Trutakna based on the protein levels in their urine, measured by the urinary protein-to-creatinine ratio (UPCR) test.
Trutakna’s accelerated approval is supported by data from an interim analysis of the phase 3 Origin 3 trial, which linked the drug to a statistically significant 42% reduction in UPCR compared with placebo at week 36.
To win a full FDA approval, an IgAN drug needs to show it can slow disease progression, as measured by changes in estimated glomerular filtration rate (eGFR). While the timeframe for that confirmatory eGFR evidence was put at about two years for past cases, including Voyxact, Vera said it recently reached an agreement with the FDA to conduct that analysis earlier.
The FDA signed off on that plan “because the effect size of atacicept’s impact on eGFR,” Fordyce said. In a phase 2b study, atacicept showed it could stabilize eGFR among patients who were expected to see a decline.
“We asked the question, is it really necessary to run that trial where you have over 400 patients going for two years, if that separation is very meaningful before two years,” Fordyce said. “We’ve questioned the ethics of continuing patients on placebo, rather than watch them go on to dialysis on placebo.”
In Vera’s Origin phase 2b trial, patients who took atacicept experienced an average annualized eGFR decline of 0.6 mL/min/1.73 m² over 96 weeks, which matches the natural aging decline in healthy adults. That eGFR number was accompanied by a 52% absolute reduction in proteinuria as measured by UPCR versus baseline.
“What’s really important for value for patients in the field is durable eGFR stability over time,” Fordyce said. “That’s what’s different about atacicept.”
Sizing up competition
However, that competitive edge from a midphase trial appears to be shrinking. In a July 1 announcement, Otsuka said Voyxact demonstrated statistically significant stabilization of kidney function, “with evidence of improvement” over two years in its phase 3 Visionary trial. Although the Japanese pharma didn’t spell out the exact data, it added that the outcomes “align with the KDIGO 2025 IgAN Guidelines of reducing kidney function decline to near physiological levels (<1 mL/min/1.73 m² per year).”
Just a month before that, detailed interim eGFR data from the phase 3 Visionary trial showed an annualized slope of eGFR indicating a kidney function decline of 3 mL/min/1.73 m² over 48 weeks.
Previously, in Novartis’ phase 3 Applause-IgAN study, Fabhalta demonstrated an annualized eGFR slope of negative 3.1 mL/min/1.73m² over 24 months. Based on the data, the FDA has accepted Novartis’ application, granting priority review for a traditional, full approval.
Direct cross-trial comparisons are flawed because of varying patient characteristics, but industry watchers perform them anyway to understand each product’s profile in a competitive landscape.
Otsuka’s latest readout is poised to escalate the market battle between its APRIL-only agent and Vera’s BAFF/APRIL dual inhibitor. Otsuka expects to finish a rolling submission with the FDA this year. Vera’s confirmatory data are expected in the third quarter with potential to support a regulatory filing before the end of the year, as its phase 3 trial continues toward its two-year eGFR analysis.
Meanwhile, more BAFF/APRIL inhibitors are lining up. In a direct threat to Vera, Vertex Pharmaceuticals’ povetacicept has posted a 49.8% reduction in UPCR compared with placebo at week 36 of a phase 3 trial. The FDA is scheduled to deliver a verdict on the med in IgAN by Nov. 30, 2026.
In a recent conversation with Jefferies, Krzysztof Kiryluk, M.D., chief of Nephrology at Columbia University, suggested that differentiation remains elusive among BAFF/APRIL drugs, and that two-year eGFR data will be critical for each product’s market positioning.
“If efficacy and eGFR outcomes are equivalent, differentiation will hinge on safety, dosing convenience (frequency of admin), monitoring requirements (for [anti-drug antibodies]/IgGs, if mandated) and insurance coverage/pricing,” according to a June 21 Jefferies note summarizing the conversation.
“Our understanding of the market is that there’s real excitement about the overall class of B cell modulation,” Fordyce told Fierce. “The most important thing, I think, is safety, and having placebo-like safety is important.”
The Vera exec suggested that IgAN likely will not see a dominant drug controlling a substantial share, and that the market is large enough for multiple agents.
A sizeable opportunity in IgAN and beyond
Vera’s conservative estimate has framed IgAN’s prevalence at 160,000 patients in the U.S. and an incidence rate of 5,000 per year. The California biotech is targeting about half of the entire population, or about 9,000 patients, who are fast progressors, as those enrolled in the company’s clinical trials.
Using Otsuka’s pricing for Voyxact, Vera estimates the IgAN market is worth about $20 billion in the U.S. alone.
“We are working to be the leader in the space,” Fordyce said. “Commercial launch of a new category of medicines is not a switch that turns on at launch, it’s something that’s been built over years.”
Over the past few years, Vera has built physician awareness around Trutakna at medical meetings, and it hired its full sales force about three months ago with multiple blockbuster launches in their experience, Fordyce said.
Vera also believes that Trutakna’s mechanism holds potential in other autoantibody-driven kidney diseases such as membranous nephropathy, in which antibodies attack the small glomeruli filters in the kidneys, and autoimmune-driven focal segmental glomerulosclerosis (FSGS), according to Fordyce.
The BAFF/APRIL drug class has shown promise in other autoimmune disorders outside the kidney, as well. Vor Bio recently in-licensed a rival BAFF/APRIL drug, telitacicept, from China’s RemeGen, and it’s prioritizing myasthenia gravis and Sjögren’s disease for global phase 3 development. The drug is already approved in multiple indications, including IgAN, in China.
For now, Fordyce is not looking to cast a broad net for Trutakna.
“We think in the scaling and building of our company that a stepwise approach, starting with leadership in IgAN and moving into adjacent autoantibody-driven kidney disease, builds real organic value and leverages the operational excellence that we’ve been building for years,” Fordyce said. “We can say that we can do everything all at once, but we like to do what we say.”
Fordyce is already thinking about improving on Trutakna. Last year, the company licensed a next-generation fusion protein targeting BAFF and APRIL from Stanford University for an undisclosed sum. Preclinical data for the asset, coded VT-109, suggest “very infrequent dosing on the order of quarterly or less frequently,” according to Fordyce, who stressed that the asset remains in the preclinical stage. Trutakna is administered via a self-administered autoinjector every week, whereas Otsuka’s Voyxact and Vertex’s povetacicept are both administered once every four weeks.
“What it reflects is confidence that dual BAFF/APRIL inhibition, as led by atacicept, is an enormous new category,” Fordyce said, “and Vera is going to continue to invest in that category for sustained leadership in the space.”