First, a reminder where the name ‘Berger’s disease’ or Morbus Berger comes from. It was Jean Berger, a French pathologist and doctor, who initially identified IgA deposits on the glomeruli of nephritic patients. This was not so long ago; his publication (in French) dates from 1968.[1]
Now the race is heating up among all those newer treatments for IgA nephropathy, also known as IgAN. The market is forecast to explode to over US$ 3.4 bio within the next 8 years. A few drugs are already on the market with many more still to come. The MoA of these drugs is quite diverse. Some target the renal vasculature, others are immune inhibitors. Some are complement blockers and others are degraders of (pathologic) IgA.[2] An overview of this emerging landscape is provided in a recent publication by Floege et al.[3]
The race is heating up, especially among the 3 BAFF/APRIL inhibitors, all of which are in late stage development vying for approval in the US with the most competitive label. We are, of course, talking about atacicept, telitacicept, and povetacicept, together known as the tacicepts. Of the three, atacicept has been around in development the longest. But it was telitacicept that beat atacicept to the market, at least in China. Povetacicept is the third wheel on this tricycle.
In the months ahead we will be inundated with TV ads with actors advising us to do urine dipsticks for hematuria and proteinuria and – talk to your doctor! While the disease, IgAN, is more prevalent in SEA and Japan than in Western countries, companies still stand to make most of their money with a US approval, not a China label. Such is the effect of pricing restrictions in China that it more than offsets the ‘volume effect’ of a much larger population and a higher disease burden.
The global market for IgAN is forecast to reach US$ 3.238 bio by 2033 by one report, and as high as US$ 4.12 bio by 2035 in another. [4],[5]
Here we provide our impartial no-hype comparison of the efficacy profiles of the 3 tacicepts. We are fairly certain that all 3 drugs will be efficacious in IgAN, achieving significant reduction in proteinuria and hematuria. There may be some numerical differences but reduction in proteinuria by approx. 50% is feasible with all 3 drugs. The big unknown is their longer-term effect on GFR – we just do not have enough data to tell whether and how much the slope returns to a ‘normal’ age-appropriate decline.
IgAN is a much under-diagnosed condition that progresses to kidney disease in an insidious manner. Many patients are asymptomatic and less than half progress to CKD in a more aggressive fashion. There are many good reviews in the recent literature; as mentioned, interest in the disease has risen exponentially in recent years, because new treatments have emerged.[6] There still is no approved tacicept on the US market, but one can safely assume that we will see fierce competition, a lot of posters and teasers at the upcoming ASN Kidney Week meeting in Houston later this month.
Here is a direct comparison of the 3 contenders based on released Phase 3 trial data. This table reflects the current status (November 2025), but we will periodically update the information and reduce the greyed-out areas as more Phase 3 info becomes available.
Note the following:
- we can take the IgA-reducing activity of tacicepts for granted; numerous studies confirm a significant percent lowering of S-IgA with this class of drugs
- so far, there are no published peer-reviewed Phase 3 data for any of the tacicepts. The telitacicept Phase 3 trial is a China-only trial and as such needs confirmation
- many articles describe case series and ‘real world’ experiences; we will not comment on these except to say that the reports from Chinese patients (all for telitacicept) are confirmatory of what is already known from clinical Phase 2 trials
- we are not aware of any IgAN-specific FDA Guidance that would codify criteria for enrollment and evaluation of efficacy. Traditionally, FDA used eGFR as the clinically relevant kidney parameter for primary efficacy; however, this is no longer the case. Proteinuria reduction (or improvement of UPCR) can serve as a surrogate endpoint for preliminary/conditional approval, with a full approval later based on GFR benefit.
- Even this 2-step procedure may change in the future. An expert data review and a recent publication by FDA regarding FSGS trials suggest that reduction of proteinuria is an acceptable surrogate given a strong correlation with GFR.[7],[8]
- it seems that demonstrating a reduction in UPCR at the 36 wk / 9-mo timepoint is now the norm for Phase 3 IgAN programs.
So far, relevant differentiating features are hard to discern among the 3 tacicepts, but less frequent dosing could become a big advantage for povetacicept. This prolonged efficacy is not a consequence of a higher MW or extended half-life but seems to reflect stronger and longer target engagement. Such target mediated drug disposition (TMDD) is not new for biologicals. It explains why povetacicept can be dosed lower and at longer dosing intervals.[13]
ABBREVIATIONS
ADA anti-drug antibody
APRIL a proliferation-inducing ligand
ASN American Society of Nephrology
BAFF B-cell activating factor
BL baseline
CKD chronic kidney disease
eGFR estimated glomerular filtration rate
FSGS focal segmental glomerulosclerosis
GdIgA galactose-deficient IgA
IA interim analysis
IgAN immunoglobulin A nephropathy
MW molecular weight
PBO placebo
SEA South East Asia
TMDD target mediated drug disposition
UPCR urine protein to creatinine ratio
REFERENCES
[1] Berger J, Les depôts intercapillaires d’IgA-IgG. J Urol Nephrol (Paris). 1968 Sep;74(9): 694
[2] Noor S. IgA nephropathy: A review of existing and emerging therapies. Front. Nephrol. 3:1175088, 2023
[3] Floege J. Treatment of patients with IgA nephropathy: a call for a new paradigm. Kidney Internat 107, 4: 640, 2025
[4] https://www.datamintelligence.com/research-report/iga-nephropathy-treatment-market (accessed 10/26/2025)
[5] https://www.marketresearchfuture.com/reports/iga-nephropathy-treatment-market-24490 (accessed 10/26/2025)
[6] Hassler J. IgA nephropathy: A brief review. Seminars in diagnostic Pathology 37: 143, 2020
[7] Thompson A. Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy. Clin J Am Soc Nephrol 14: 1, 2019
[8] Mariani L. Proteinuria as an Endpoint in Clinical Trials of Focal Segmental Glomerulosclerosis. Am J Kidney Dis. 2025; 85: 610
[9] Vera Therapeutics Announces Atacicept Achieved 46% Proteinuria Reduction in ORIGIN Phase 3 Trial in Adults with IgA Nephropathy. Press Release June 2, 2025
[10] Telitacicept Achieved Primary Endpoint in Phase 3 Clinical Study for IgA Nephropathy. Vor Bio Press Release August 27, 2025
[11] Barratt J. J Am Soc Nephrol 2024 Oct 26:10.1681/ASN.0000000541
[12] https://www.globenewswire.com/news-release/2025/08/27/3139971/0/en/Telitacicept-Achieved-Primary-Endpoint-in-Phase-3-Clinical-Study-for-IgA-Nephropathy.html
[13] Davies R. A first-in-human, randomized study of the safety, pharmacokinetics and pharmacodynamics of povetacicept,an enhanced dual BAFF/APRIL antagonist, in healthy adults. Clin Transl Sci. 2024;17: 1
