Vera Therapeutics has put a two-year kidney function dataset behind its bid for IgAN full approval. On 15 September 2026, the company reported the final efficacy analysis of the Phase 3 ORIGIN 3 trial. The trial tested Trutakna (atacicept-vymj) in adults with primary IgA nephropathy (IgAN). Vera says it met all prespecified endpoints. It plans a supplemental Biologics License Application in the fourth quarter of 2026.
The readout matters beyond one company. Several IgAN medicines reached the US market on proteinuria, a surrogate marker. Each must now show that it slows the loss of kidney function. That confirmatory step is where the commercial field will be sorted. In the UK, meanwhile, the regulatory picture is far less advanced.
What ORIGIN 3 Reported on 15 September
Vera’s 15 September announcement covers 428 patients. At 52 weeks, mean estimated glomerular filtration rate (eGFR) changed by minus 0.1 mL/min/1.73m² on Trutakna. The placebo group changed by minus 5.7. The treatment effect was 5.6 (95 per cent CI 3.7 to 7.5; p<0.0001).
Through 104 weeks, the annualised eGFR slope was minus 0.6 on Trutakna and minus 5.6 on placebo. That gives a difference of 5.0 mL/min/1.73m² per year (95 per cent CI 3.6 to 6.5; p<0.0001). Composite kidney disease progression events numbered 11 on Trutakna against 38 on placebo. Vera reports a hazard ratio of 0.24 (95 per cent CI 0.12 to 0.48).
Dialysis for at least 30 days, transplant or death occurred in no Trutakna patients and eight placebo patients. Vera also reports statistically significant reductions in proteinuria, galactose-deficient IgA1 and haematuria. Richard Lafayette is a principal investigator for ORIGIN 3. He is Professor of Medicine, Nephrology, and Director of the Glomerular Disease Center at Stanford University Medical Center. “Prevention of kidney failure or kidney-related death is the ultimate goal,” he said in the release.
Vera calls ORIGIN 3 the first reported Phase 3 IgAN trial with FDA alignment on an earlier final analysis. The company says this gives placebo patients an earlier chance to move onto open-label Trutakna. Marshall Fordyce is Vera’s Founder and Chief Executive. “We plan to submit the supplemental BLA in the fourth quarter of this year. We look forward to the potential full approval of TRUTAKNA in 2027,” he said.
What the Release Did Not Quantify
The release leaves several gaps that matter for any IgAN full approval review. It does not define the components of the composite progression endpoint. It gives no proteinuria, galactose-deficient IgA1 or haematuria figures, only statistical significance. Nor does it say how many patients completed 104 weeks of treatment.
It also reports no serious adverse event rates, no deaths by arm outside the composite, and no discontinuation rates. Vera says detailed results will appear at an upcoming scientific congress. The release does not name the congress.
Safety: What the Release Says and What the Label Adds
Vera’s release says rates of overall adverse events and infections were similar between the two groups. It reports no opportunistic infections and no “clinically relevant hypogammaglobulinemia.” The approved label gives a fuller picture.
The US prescribing information lists two warnings. The first covers immunosuppression and increased risk of infections. The second covers immunisation, and says live vaccines are not recommended within 30 days before or during treatment.
On the label, infections occurred in 32 per cent of Trutakna patients versus 28 per cent on placebo. Local administration reactions affected 30 per cent against 5 per cent. Injection site reactions alone affected 19 per cent against 2 per cent. By week 36, serum IgG had fallen 36 per cent from baseline. IgA fell 64 per cent and IgM fell 75 per cent. Anti-drug antibodies developed in 43.2 per cent of patients, with no clinically significant effect reported.
The label also records the current limit of the evidence. “It has not been established whether TRUTAKNA slows kidney function decline over the long-term,” it states. The FDA granted accelerated approval on 7 July 2026. The indication is to reduce proteinuria in adults at risk of progression. That limitation is what an IgAN full approval filing would seek to remove.
How the IgAN Full Approval Race Stands
LSDN covered the July accelerated approval when it landed. Two months on, the IgAN full approval question now separates the class into four positions.
Novartis’s Fabhalta (iptacopan) has already converted. Novartis announced FDA traditional approval on 17 July 2026. The new indication is to slow kidney function decline in adults with primary IgAN at risk of progression. Novartis cites an annualised eGFR change of minus 3.0 on Fabhalta against minus 5.7 on placebo over 24 months.
Otsuka’s Voyxact (sibeprenlimab) is part way through its filing. Its rolling supplemental application for traditional approval was already under way by June 2026. On 3 August 2026 Otsuka said the two-year data marked another milestone in that submission.
In VISIONARY, the key secondary endpoint was eGFR slope over 24 months. It was plus 0.3 against minus 4.2. Otsuka called that difference the largest treatment effect reported in a Phase 3 IgAN trial. It made that claim on 3 August, six weeks before the ORIGIN 3 readout.
The IgAN full approval path is less clear for Novartis’s Vanrafia (atrasentan). On 13 February 2026, Novartis reported a Week 136 eGFR difference of 2.39 versus placebo. The two-sided p value was 0.057. At Week 132, the end of treatment, the difference was 2.59 with a nominal p value of 0.039. Novartis said it “plans to submit for traditional approval in 2026.” LSDN found no traditional approval for Vanrafia as at 17 September 2026.
Vertex’s povetacicept, a second dual BAFF and APRIL inhibitor, has not yet reached market. The FDA accepted its application for accelerated approval in June. The target action date is 30 November 2026, as tracked in LSDN’s FDA decision calendar. Vertex says RAINIER continues to a final analysis. Its primary endpoint there is total eGFR slope through Week 104. That is the dataset its own IgAN full approval case will rest on.
These trials differ in population, baseline kidney function, background therapy and duration. ORIGIN 3 enrolled a population that was 55 per cent Asian, according to the label. None of the trials was designed for cross-trial comparison, and no conclusion about relative efficacy should be drawn.
Market Reaction on 15 September
Investors gave the readout a mixed reception. Vera shares rose in premarket trading on 15 September. They then reversed during the regular session, according to Invezz and Schaeffer’s Investment Research. Invezz described a “sell the news” pattern. It pointed to the July approval and gains already priced in. Outlets reported different percentages across different windows, so LSDN reports the direction only.
Vera also used the release to promote early uptake. Chief Commercial Officer Matt Skelton cited over 350 patient start forms in the launch’s first ten weeks. That is a company metric, not audited sales.
The UK Picture: Trial Sites, but No Disclosed Filing
UK patients helped generate the ORIGIN 3 evidence. A Health Research Authority research summary records a favourable ethics opinion on 21 December 2023. It came from the Yorkshire and The Humber, Leeds East Research Ethics Committee, reference 23/YH/0259. The protocol describes a 104-week double-blind period followed by a 52-week open-label extension.
Neither the 15 September release nor Vera’s 10 August business update mentions a UK, EU or other ex-US filing. LSDN found no NICE project for atacicept as at 17 September 2026. No filing outside the US has been disclosed. LSDN draws no inference from that silence and found no company explanation.
One IgAN medicine has already left the UK appraisal pipeline. NICE suspended its appraisal of iptacopan for primary IgAN on 1 April 2026. NICE says the company advised that it is “no longer pursuing a Marketing Authorisation Application” from the MHRA. NICE adds that this applies “for this indication at this time.” That is the same medicine that won US traditional approval in July.
What NICE does recommend is narrower. TA1128, published on 4 February 2026, recommends targeted-release budesonide as an add-on. Patients need a urine protein-to-creatinine ratio of 90 mg/mmol or more, or 1.0 g a day or more. Optimised standard care must include the highest tolerated renin-angiotensin system inhibitor or a dual endothelin angiotensin receptor antagonist.
TA1074 recommends sparsentan, that dual antagonist, at a threshold of 85 mg/mmol or 1 g a day. The committee noted “considerable uncertainty” about its longer-term effects on kidney function. In LSDN’s reading, confirmatory eGFR data are precisely what would test that uncertainty for any newcomer. NICE has not framed it that way for atacicept.
What UK Registry Data Add
UK registry data explain why two-year kidney function results carry such weight. The UK National Registry of Rare Kidney Diseases (RaDaR) followed 2,439 patients. The analysis was published in CJASN in 2023. Half reached kidney failure or died during the study period. Median kidney survival was 11.4 years.
Jonathan Barratt of the University of Leicester was senior author. The authors concluded that “few patients” were “expected to avoid kidney failure in their lifetime.” The authors found almost all patients at risk unless eGFR loss stays at 1 mL/min/1.73m² a year or less.
The ORIGIN 3 slope of minus 0.6 sits within that threshold on its point estimate. Its confidence interval runs from minus 1.6 to 0.4.
Vera makes a similar point in its release. It says the results align with the KDIGO goal of keeping decline below 1 mL/min/1.73m² a year. Otsuka made the same KDIGO claim for VISIONARY in August. A registry threshold and a two-year trial slope are not directly comparable measures.
What to Watch Next
For Vera, the next markers are the named congress presentation, the supplemental filing and the FDA’s review timetable. The composite endpoint definition and the serious adverse event data will matter as much as the headline slope. Otsuka’s rolling submission and Novartis’s Vanrafia filing will show how the FDA weighs a borderline eGFR result.
There is a precedent for IgAN full approval on a borderline endpoint. Fierce Pharma reported that the FDA converted Filspari to full approval in 2024. Its PROTECT trial had missed statistical significance on eGFR at two years.
Vertex’s 30 November decision would bring a second dual BAFF and APRIL inhibitor to the US market. In England, the question is different. The two NICE recommendations covered here each carry a proteinuria threshold. For now, the IgAN full approval race is a US contest. Whether its newest entrants will reach UK patients is not yet clear.
