New data from the open-label extension of the ORIGIN trial suggests that atacicept, a dual BAFF/APRIL inhibitor, could significantly slow the rate of kidney function decline in patients with IgA nephropathy, potentially mirroring the physiological aging process of kidneys without the disease. The findings, presented at the American Society of Nephrology’s Kidney Week 2024, highlight atacicept's potential as a disease-modifying therapy.
Sustained Reductions in Key Disease Markers
The ORIGIN trial's extension demonstrated that atacicept was associated with sustained reductions in several key markers of IgA nephropathy, including galactose-deficient IgA1 (Gd-IgA1), hematuria, and urine protein to creatinine ratio (UPCR). The 96-week data revealed a 66% mean reduction in Gd-IgA1 levels and a 52% reduction in UPCR. The percentage of patients with hematuria also decreased significantly.
Impact on Kidney Function
Notably, the mean eGFR annualized slope was -0.6 (SE, 0.5) mL/min/1.73m2 per year. According to principal investigator Jonathan Barratt, PhD, Mayer Professor of Renal Medicine at the University of Leicester, this indicates a slowing in the loss of kidney function to a level associated with physiological aging. "So, actually, back to almost health for kidneys, and this is in a high-risk group of patients with IgA nephropathy, where, traditionally, we would expect them to lose 5 to 6 mLs of GFR every year. So, really astounding results and something that I certainly didn't think I was going to see in terms of new therapies."
Trial Design and Patient Population
The phase 2b ORIGIN trial initially enrolled participants from 65 centers across 13 countries, who were administered atacicept or placebo weekly for 36 weeks. Following this, patients entered an open-label extension where all received atacicept 150 mg for an additional 60 weeks. Of the 113 patients who received at least one dose of atacicept, 90% completed the open-label extension. The cohort had a median age of 37 years, with a mean baseline eGFR of 62 mL/min/1.73m2 and a mean UPCR of 1.8 g/g.
Safety Profile
The safety data from the 60-week open-label extension period showed a similar proportion of patients with treatment-emergent adverse events (77%) compared to the atacicept group during the 36-week double-blind period (73%) and the placebo group (82%).
Future Implications
Atacicept is currently under evaluation in a phase 3 trial, ORIGIN. Vera Therapeutics announced the completion of enrollment for this trial in September 2024, with topline results anticipated in Q2 2025. These findings could represent a significant advancement in preventing kidney failure in patients with IgA nephropathy.
