Atacicept

96-week ORIGIN trial data shows atacicept's potential in treating IgA nephropathy, with sustained reductions in Gd-IgA1 levels, hematuria, and UPCR, and a minimal decline in eGFR. Atacicept's weekly self-administered injection and ongoing phase 3 trials could redefine treatment outcomes.

Atacicept shows potential to prevent kidney failure in IgAN patients, with long-term stabilization of kidney function observed in ORIGIN Phase 2b study, published in the Journal of the American Society of Nephrology.

A randomized, double-blind, phase III clinical trial (Aug 2019–Oct 2021) in Iran compared Xacrel (300 mg, then 600 mg every 24 weeks) to Ocrevus (same regimen) in MS patients. Primary outcome was ARR reduction equivalence at week 48. Secondary outcomes included disability progression, relapse-free patients, MRI lesion changes, and safety assessments. The study adhered to ethical and regulatory standards.

Otsuka's anti-APRIL antibody sibeprenlimab showed significant reduction in uPCR in a phase 3 trial for IgA nephropathy, prompting potential FDA submission. Final results expected in 2026. Competitors include Novartis' zigakibart, Vertex's povetacicept, and Vera's atacicept.

IgA nephropathy (IgAN) is a common autoimmune kidney disease characterized by IgA deposits, leading to progressive damage and chronic kidney disease (CKD). 40-53% of patients progress to end-stage renal disease (ESRD) within two decades, necessitating interventions like dialysis or transplantation. The treatment landscape for IgAN is evolving with ongoing phase 3 trials for 11 agents, including budesonide and sparsentan, which have received FDA approval. Early detection and intervention are crucial to delay progression, reduce healthcare costs, and improve patient outcomes.

Vera Therapeutics to host R&D Day in NY on Oct 2, 2024, featuring experts discussing atacicept R&D beyond ORIGIN Phase 2b/3. Event precedes 96-week ORIGIN study data presentation in Q4 2024. Atacicept received FDA Breakthrough Therapy Designation for IgAN treatment.

Vera Therapeutics completed early enrollment for ORIGIN 3 trial of atacicept in IgAN, with 200 participants for 36-week UPCR primary endpoint. Topline results expected Q2 2025, and 96-week data from ORIGIN Phase 2b trial to be presented Q4 2024.

Lena Tholen, Meinhard Hasslacher, and Neeraj Pakala discuss early process decisions' impact on novel protein therapeutics, emphasizing cell line selection, regulatory scrutiny, and monitoring key attributes. They highlight the importance of early formulation and product stability studies, and the need for robust control strategies to avoid later-stage issues.