Long-Term Results from an Open-Label Extension Study of Atacicept for the Treatment of IgA Nephropathy


Barratt J., Barbour S., Brenner R., Cooper K., Wei X., EREN N., ...More

Journal of the American Society of Nephrology, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2024
  • Doi Number: 10.1681/asn.0000000541
  • Journal Name: Journal of the American Society of Nephrology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, CAB Abstracts, CINAHL, MEDLINE, Veterinary Science Database
  • Keywords: IgA nephropathy, kidney disease
  • Kocaeli University Affiliated: Yes

Abstract

Background B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) play key roles in the pathogenesis of IgA nephropathy. Atacicept is a novel fully humanized fusion protein, self-administered at home by subcutaneous injection, that binds and inhibits BAFF and APRIL. By inhibiting BAFF and APRIL, atacicept targets the underlying B-cell-mediated pathogenesis driving disease progression. This study evaluated the long-term efficacy and safety of atacicept in patients with IgA nephropathy over 96 weeks. Methods Participants with IgA nephropathy who received atacicept (25, 75, or 150 mg) or placebo in a 36-week phase 2b, randomized, blinded trial were enrolled in an open-label extension study 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, urine protein-creatinine ratio (UPCR), and eGFR over 96 weeks. Long-term safety data were also evaluated. Results There were 113 participants (67 [59%] male; 46 [41%] female) who ranged in age from 18 to 67 years who received ≥1 atacicept dose. Over 96 weeks, safety data demonstrated that atacicept was generally well tolerated. There were also sustained reductions (mean±SEM) in Gd-IgA1 (-66%±2%), percentage of participants with hematuria (-75%; 95% confidence intervals, -87 to -59; in participants with baseline hematuria), and UPCR (-52%±5%). The mean annualized slope of eGFR was -0.6±0.5 ml/min per 1.73 m2 through 96 weeks. Conclusions Atacicept was also well tolerated over the duration of the study. Atacicept treatment reduced Gd-IgA1, hematuria, and UPCR with stabilization of eGFR through 96 weeks.