Kidney Week

Abstract: SA-OR102

Long-Term Results from the ORIGIN Phase 2b Study of Atacicept for the Treatment of IgA Nephropathy (IgAN)

Session Information

• Late-Breaking Science Orals - 2
  October 26, 2024 | Location: Room 6C, Convention Center
  Abstract Time: 05:20 PM - 05:30 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Barratt, Jonathan, University of Leicester, Leicester, United Kingdom

Jonathan Barratt, MBChB, PhD

• Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada

Sean Barbour, MD, MS, MSc

• Brenner, Robert M., Vera Therapeutics, Inc., Brisbane, California, United States

Robert M. Brenner, MD

• Cooper, Kerry, Vera Therapeutics, Inc., Brisbane, California, United States

Kerry Cooper, MD

• Wei, Xuelian, Vera Therapeutics, Inc., Brisbane, California, United States

Xuelian Wei

• Eren, Necmi, Kocaeli Universitesi, Kocaeli, Turkey

Necmi Eren, MD

• Floege, Jürgen, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Nordrhein-Westfalen, Germany

Jürgen Floege, MD

• Jha, Vivekanand, The George Institute for Global Health India, New Delhi, Delhi, India

Vivekanand Jha, MD

• Kim, Sung Gyun, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea (the Republic of)

Sung Gyun Kim, MD, PhD

• Maes, Bart D., AZ Delta vzw, Roeselare, West-Vlaanderen, Belgium

Bart D. Maes, MD, PhD

• Phoon, Richard K S, The University of Sydney, Sydney, New South Wales, Australia

Richard K S Phoon, MBBS

• Singh, Harmeet, Western Nephrology, Arvada, Colorado, United States

Harmeet Singh, MD, FASN

• Tesar, Vladimir, Univerzita Karlova, Praha, Czechia

Vladimir Tesar, MD, PhD, MBA, FASN

• Lafayette, Richard A., Stanford University, Stanford, California, United States

Richard A. Lafayette, MD

Group or Team Name

• ORIGIN Phase 2b Study Team.

Background

B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) play key roles in IgAN pathogenesis. Atacicept is a humanized TACI-Fc fusion protein that inhibits both BAFF and APRIL and is self-administered at home by subcutaneous injection. The ORIGIN Phase 2b study met the primary endpoint 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. This analysis reports 96-week results from the open-label extension (OLE).

Methods

Participants with IgAN who received atacicept or placebo in the 36-week Phase 2b, randomized, blinded study period were enrolled in an OLE and received atacicept 150 mg for an additional 60 weeks. Key efficacy outcomes were changes in galactose-deficient IgA1 (Gd-IgA1), percentage of participants with hematuria, UPCR, and eGFR over 96 weeks. Long-term safety data were also evaluated.

Results

There were 113 participants who received ≥1 atacicept dose. Over 96 weeks, there were sustained reductions (mean ±SE) in Gd-IgA1 (-65.9% ±1.7%), the percentage of participants with hematuria (-75.0%, 95% CI -87.3, -58.8; in participants with baseline hematuria), and UPCR (-52.2% ±4.7%). Importantly, long-term eGFR was maintained near baseline levels with a mean annualized slope of -0.6 ±0.5 mL/min/1.73m²/year at 96 weeks (Figure). Safety data showed atacicept was generally well tolerated.

Conclusion

Gd-IgA1, hematuria, and UPCR reductions with eGFR stabilization through 96 weeks demonstrate that atacicept offers a potentially safe, long-term, disease-modifying treatment for IgAN. Specifically, the conversion of an eGFR profile in patients with IgAN from one of steady decline to one representative of the general population without kidney disease¹ supports the potential of atacicept to decrease the high lifetime risk of kidney failure in patients with IgAN.
1. Baba M. PLoS One 2015.

Funding

• Commercial Support – Vera Therapeutics, Inc.