Two posters on tacicepts caught our eyes.
First is the Tumlin publication on povetacicept, an oral presentation in the “Late-Breaking Research” session. This is an interim look at Phase 1b study data reporting on 17 IgAN patients treated for 48 weeks with a dose of 80 mg and 30 patients with a 240 mg dose; both arms are dosed SC q4w.[1]
Given the small patient cohort, open study design and absence of a placebo arm, this is just a first glimpse at efficacy. As it was a late-breaker, nobody bothered to check for typos either.
We are told that the GFR ‘stabilized’; UPCR, hematuria and Gd-IgA1 levels were reduced. These early data confirm what we already know about the class of BAFF/APRIL inhibitors; namely, that povetacicept does well on all accounts. It is too early to make any quantitative comparisons or claims. No need to update our tacicept comparison table from a prior blog yet, as we are only tracking pivotal Phase 3 trials. We are puzzled, however, by the lack of a dose response despite the 3-fold difference in dosing regimens.
We interpret these data as a signal or trend in the right direction.
Second, the Lafayette poster is about the atacicept ORIGIN-3 study, labeled correctly a “High-Impact Clinical Trial”.[2] Here, dosing was150 mg SC weekly. The 36-wk results are indeed impressive but wait, where are the new data? Could this be a duplicate publication?
A recent NEJM article by Lafayette and the Vera team provided outcome information on the same population, now with graphs stacked vertically [3]:
While the data for UPCR and Gd-IgA1 reductions are identical, we noticed some subtle changes to the hematuria graph: atacicept no longer comes out at -81.0% but at -82.1%, while hematuria in the placebo arm now shows a -19.4% reduction, somewhat less than the -20.7% quoted in the (earlier) NEJM article. Of note, the odds ratios are nevertheless unchanged.
Both graphs and publications deal with the same IA of 203 patients (atacicept N=106; placebo N=97) at Week 36. Why this difference?
Usually, we are not sticklers about a 1-2% deviation in results from an IA, and neither should you be. Data correction of a single patient outcome may account for such small discrepancies. What seems like a duplicate publication is probably meant to be an update, a correction of sorts, to a secondary endpoint.
This is, however, more than a routine IA. This data set with UPCR reduction at 36-wk as the primary efficacy outcome for ORIGIN-3 is at the core of Vera’s FDA submission. The 203-patient FAS that constitutes the IA should be rock-solid by now (see timeline of primary study completion) and we should be told which graph is correct.
The Vera team is now compiling the atacicept NDA dossier. We are anxious to learn the final results.
ABBREVIATIONS
Gd-IgA1 galactose-deficient IgA1
IA interim analysis
FAS full analysis set
UPCR urinary protein to creatinine ratio
REFERENCES
[1] Tumlin J. Efficacy and Safety of Povetacicept in Patients with IgAN and Primary Membranous Nephropathy (pMN) at 48 Weeks of Treatment: The RUBY-3 Study. SA-OR091. JASN 36(10S):10.1681/ASN.20253s04myx7, October 2025
[2] Lafayette R. ORIGIN 3: A Phase 3 Trial of Atacicept in IgAN. TH-OR083JASN (10S):10.1681/ASN.202589fw4b2p, October 2025.
[3] Lafayette R. A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy. NEJM. 2025 Nov 6. doi: 10.1056/NEJMoa2510198.
