Atacicept May Offer Durable Benefits in IgAN with Ongoing Use, with Jonathan Barratt, MD, PhD

Fresh on the heels of ORIGIN phase 3 topline results, new follow-up data from the phase 2b ORIGIN study highlight the consequences of atacicept discontinuation in patients with IgA nephropathy (IgAN), underscoring the potential need for sustained B-cell–targeted therapy in this population.

Presented at the 62nd European Renal Association (ERA 2025) Congress, the analysis evaluated changes in galactose-deficient IgA1 (Gd-IgA1) and estimated glomerular filtration rate (eGFR) during the 26-week period after stopping atacicept.

“What this is showing us is that atacicept, over the timeframe that it was given in the phase 2 trial, is not a curative treatment—it suppresses and controls the disease, and that you are going to need to use this drug on a long term basis to maintain control of IgA nephropathy,” explained lead investigator Jonathan Barratt, MD, PhD, the Mayer Professor of Renal Medicine at the University of Leicester, in an interview with HCPLive Nephrology.

The phase 2b ORIGIN study was a double-blind, randomized trial with a population of 116 adults with biopsy-confirmed IgAN, proteinuria greater than 0.75 grams per day or UPCR greater than 0.75 grams per gram, and eGFR greater than or equal to 30 mL/min/1.73 m² despite optimized renin–angiotensin system inhibition. Patients received atacicept or placebo for up to 36 weeks, followed by an open-label extension (OLE) with atacicept 150 mg weekly for up to 60 additional weeks. After completing 96 weeks of treatment, 103 participants entered a 26-week post-treatment follow-up period with evaluations at weeks 12 and 26.

The original results of the trial demonstrated use of atacicept was associated with a statistically significant and clinically meaningful UPCR reduction compared to placebo at 24 weeks, with a further reduction and eGFR stabilization through 36 weeks.

At ERA 25, Barratt presented data from participants who had available Gd-IgA1 and eGFR values at week 96 and follow-up. This data suggested serum Gd-IgA1 increased by 90% at week 12 and by 117% at week 26 post-treatment. Additionally, eGFR declined by 1.6 mL/min/1.73 m² at week 12 and 3.9 mL/min/1.73 m² at week 26. Investigators noted no urine samples were collected during follow-up and proteinuria data were not included in this analysis.

Eligible participants are now enrolling in a new long-term OLE, ORIGIN Extend, to evaluate the effects of atacicept reinitiation. According to investigators, the next phase of research will help determine whether the observed benefits of atacicept can be consistently sustained with prolonged therapy.

Relevant disclosures of interest for Barratt included Argenx, Calliditas Therapeutics, Chinook Therapeutics, Galapagos NV, GSK, Novartis, Travere Therapeutics, and others.

References:

Barratt J, Barbour S, Brenner R, et al. ORIGIN 2b: Changes in Gd-IgA1 and eGFR After Discontinuation of Atacicept Treatment in IgA Nephropathy. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.