Kidney Compass: Atacicept for IgAN with Jonathan Barratt, MD, PhD, at Kidney Week 2024

Key Takeaways

Atacicept demonstrated significant reductions in Gd-IgA1 levels, hematuria, and UPCR, with minimal eGFR decline in IgA nephropathy patients.
The drug targets disease-causing cytokines and is administered as a weekly self-injection, enhancing long-term patient accessibility.
Ongoing phase 3 trials and extended access initiatives may redefine treatment outcomes for IgA nephropathy, marking a pivotal shift in disease management.

Neuen, Wadhwani, and Barratt discuss atacicept promise in IgA nephropathy based on phase 2b ORIGIN OLE results, at-home use, and the future of kidney disease care.

Key Timestamps

00:00 – Introduction

01:26 – Understanding Atacicept's MoA

04:30 – 96-Week ORIGIN Data

07:30 - Reaction to Data/Landscape of IgAN

10:00 – Safety Data

13:45 – Future of IgA Nephropathy Treatment and Phase 3 Trials

The release of 96-week data from the open-label extension period of the phase 2b ORIGIN trial provides evidence of the disease-modifying potential of atacicept in patients with IgA nephropathy.

Results, which were presented at the American Society of Nephrology Kidney Week 2024, indicate atacicept use was associated with sustained reductions across multiple endpoints of interest, including a 66% (SE, 2%) mean reduction in Gd-IgA1 levels, a reduction in percentage of patients with hematuria from baseline (percentage change, 75%; 95% CI, -87% to -59%), and a mean reduction in UPCR of 52% (SE, 5%). Investigators highlighted the mean eGFR annualized slope was just -0.6 (SE, 0.5) mL/min/1.73m2 per year.

“We are one step closer to preventing kidney failure in the lifetime of our patients with IgA nephropathy, which is an amazing turnaround compared to the first 50 years of knowing about this disease, when we couldn't do very much at all other than just watch them just progressively decline in kidney function [and] end up on dialysis,” explained Jonathan Barratt, MD, PhD, the Mayer Professor of Renal Medicine at the University of Leicester. “So, a massive turnaround in terms of what we potentially could achieve with the new therapies.”

At Kidney Week 2024, Barratt sat down for a special edition recording of Kidney Compass: Navigating Clinical Trials. In the episode, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, are taken on a deep dive into the results of the trial and what it means for the treatment landscape of IgA nephropathy.

As the discussion unfolds, Barratt explains atacicept’s unique approach of targeting disease-causing cytokines and highlights the drug’s practical benefit as a weekly self-administered injection, making it accessible for long-term patient use. The conversation wraps up with insights into the global impact of ongoing phase 3 trials, the sponsor’s commitment to extended access, and how these steps could redefine outcomes for patients with IgA nephropathy.

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Relevant disclosures of interest for Barratt included Argenx, Calliditas Therapeutics, Chinook Therapeutics, Galapagos NV, GSK, Novartis, and Travere Therapeutics. Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for Wadhwani include the National Institute of Diabetes and Digestive and Kidney Diseases, GSK, Calliditas and Travere Therapeutics.

References:

^{Barratt J, Barbour S, Brenner RM, et al. Long-Term Results from the ORIGIN Phase 2b Study of Atacicept for the Treatment of IgA Nephropathy (IgAN). Presented at American Society of Nephrology Kidney Week 2024. San Diego, CA. October 23-27, 2024.}
^{Campbell P. ORIGIN OLE Data Solidify Atacicept Disease-Modifying Potential for IgA Nephropathy. HCPLive. October 26, 2024. Accessed October 26, 2024. https://www.hcplive.com/view/origin-ole-data-solidify-atacicept-disease-modifying-potential-for-iga-nephropathy.}