Cemdisiran shows promise in IgA nephropathy

Monthly subcutaneous administration of cemdisiran was shown to suppress hepatic complement component 5 (C5) production, resulting in clinically meaningful improvements in proteinuria in patients with immunoglobulin A nephropathy (IgAN). The drug was well tolerated and no major safety issues occurred. These results support further evaluation of cemdisiran as a potential therapy in IgAN [1].

“IgAN is the most common type of glomerulonephritis and carries a serious lifetime risk of kidney failure,” Prof. Jonathan Barratt (University of Leicester, UK) explained. “The current treatment options are limited, and we are in high need for new therapies.” Cemdisiran is an investigational RNA interference therapeutic that suppresses liver production of C5. It is delivered SC and is in development for the treatment of complement-mediated disease. Cemdisiran was assessed in a randomised, double-blind, placebo-controlled, phase 2 study (NCT03841448). Patients with IgAN, proteinuria >1 g/24 hours, estimated glomerular filtration rate ≥30 mL/min/1.73m², stable optimal treatment ≥3 months, and no recent steroid or other immunosuppressive treatment in the past 6 months were randomised (2:1) to cemdisiran 600 mg or placebo Q4W alongside standard of care. The primary endpoint was the change from baseline to week 32 in 24-hour urine protein-to-creatinine ratio (UPCR). “We included a total of 31 patients of whom 22 were treated with cemdisiran and 9 received placebo, both with standard of care,” Prof. Barratt said. “These were patients with relatively early disease, and the vast majority were treated with renin–angiotensin–aldosterone system inhibitors (RAASis). Despite optimal treatment they had high baseline eGFR, which meant they were a high-risk population.” Treatment with cemdisiran resulted in a rapid and sustained decrease in C5 protein level and complement activity compared with placebo. Cemdisiran achieved a mean percent reduction in circulating C5 of 98.7% from baseline at week 32. The change from baseline proteinuria in 24-hour UPCR with placebo at week 32 was −37.4% (90% CI −61.0 to 0.5). The improvements in 24-hour UPCR were consistent in pre-defined subgroups. Prof. Barratt also addressed safety and tolerability of cemdisiran: “The drug was generally well tolerated. No treatment-related serious adverse events (AEs) or severe AEs occurred. The most important AEs in ≥10% of cemdisiran-treated patients were injection-site reactions (41%) and peripheral oedema (14%).”

1. Barratt J, et al. Exploratory Results From the Phase 2 Study of Cemdisiran in Patients With IgA Nephropathy. FR-OR67 ASN Kidney Week 2022, 3–6 Nov.

 

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Posted on 8 December 2022