Phase 2b Data, Phase 3 Trial Design Provide New Insight into Atacicept in IgAN


Data from multiple presentations at ASN Kidney Week 2023 offer insight into the effects of atacicept in patients with IgA nephropathy as well as the design of the phase 3 trial, which is currently enrolling.

New data on the effects of atacicept 150 mg from the phase 2b ORIGIN trial and details regarding the design of the ORIGIN 3 trial provide new insight into the potential of the agent in the management of IgA nephropathy.

In the phase 2b ORIGIN trial, receiving atacicept 150 mg, which is the same dose examined in ORIGIN 3, was associated with a mean placebo-adjusted UPCR reduction of 35% (P=.012; in the study’s intention-to-treat analysis and 43% (P=.003) in a prespecified per-protocol analysis. At the American Society of Nephrology Kidney Week 2023, additional data from the phase 2b ORIGIN trial indicated use of atacicept was associated with an increased likelihood of achieving resolution of hematuria, with 80% of the atacicept arm meeting this endpoint compared with just 5% of the placebo arm.

In ORIGIN 3, investigators randomized patients in a 1:1 ratio to self-administered subcutaneous atacicept 150 mg or placebo for 104 weeks in a double-blind period, followed by a 52-week open-label extension. Investigators aim to enroll 376 patients in the trial, with 188 randomized into each arm.

For inclusion in the trial, patients are required to be at least 18 years or older, have biopsy-confirmed IgA nephropathy, be receiving RAASi at maximally-tolerated doses for 12 weeks, a UPCR of 1.0 g/g or greater or urine protein of 1.0 grams per 24 hours, n eGFR of 30 mL/min/1.73m2 or greater.

The primary endpoint of interest for the trial is the percentage change in UPCR from baseline at 36 weeks using a mixed-effects model with repeated measurement, with annualized eGFR slope up to 104 weeks serving as the key secondary endpoint.

For more on the potential of atacicept and what the nephrology community can hope to learn from the ORIGIN 3 trial, HCPLive Nephrology sat down with study investigator Richard Lafayette, MD, founder and director of the Stanford Glomerular Disease Center, at Kidney Week 2023.

Relevant disclosures for Lafayette include Aurinia, Callidatas, Complexa, Mallinckrodt, Omeros, Pfizer, and others.


  1. Barratt J, Maes BD, Israeli RK, et al. ORIGIN 3: Pivotal Ph3 Study Evaluating Effect of Atacicept vs. Placebo on Proteinuria and Renal Function Preservation in IgA Nephropathy (IgAN). Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023.
  2. Vera Therapeutics. Vera Therapeutics presents positive data from phase 2B origin study showing resolution of hematuria in majority of patients at the American Society of Nephrology Kidney Week 2023. Vera Therapeutics. November 4, 2023. Accessed November 4, 2023.
  3. Vera Therapeutics. Vera Therapeutics to present three posters at the American Society of Nephrology Kidney Week 2023 annual meeting. Vera Therapeutics. October 13, 2023. Accessed November 4, 2023.
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