Study Supports the Efficacy, Safety of Ravulizumab for Patients with IgA Nephropathy

Credit: George Clinical

A new study demonstrated the efficacy and safety of ravulizumab for treating patients with Immunoglobulin A Nephropathy (IgAN) or Berger’s disease, presented as a late-breaking poster on November 2, 2023, at the Pennsylvania Convention Center during Kidney Week.¹

Led by Jonathan Barratt, PhD, FRCP, of the University of Leicester in Leicester, United Kingdom, the study compared ravulizumab’s efficacy and safety versus a placebo. The US Food and Drug Administration (FDA) previously approved ravulizumab-cwvz (Ultomiris) to treat the life-threatening blood disease, paroxysmal nocturnal hemoglobinuria (PNH) in patients aged ≥1 month old.²

IgAN is the most prevalent primary glomerular disease, which can progress to end-stage kidney disease, when the kidney can no longer support a body’s needs.3 The immune response releases Immunoglobulin A, a protein that helps the body fight infections. But IgAN occurs when the protein gets stuck in the kidneys causing inflammation—or in other words, glomerular damage by immune complex disposition.4 After this, the body releases proinflammatory cytokines. The investigators found inhibiting the complement system might be an effective way to reach better outcomes for the kidneys.

In the phase 2 randomized controlled trial (NCTO4564339), eligible patients were 18 – 75 years old with IgAN, an elevated protein in the urine (proteinuria), on stable maximally tolerated renin-angiotensin system inhibitors with a stale blood pressure of >3 months. The 66 patients were randomized 2:1 into the ravulizumab group (n = 43) and the placebo group (n = 23). The mean age sat at 40.1 years, 46% were female, and 21% were Asian.

The primary endpoint was the percentage change in proteinuria from baseline to 26 weeks based on 24-hour urine. The secondary endpoint included spot urine protein: creatinine ratio (UPCR), an alternative test used to detect proteinuria, as well as change in baseline to 26 weeks for estimated glomerular filtration rate (eGFR), which measures how well the kidneys work. The investigators also did a pharmacokinetic-pharmacodynamic analysis, measuring drug effects to a measure of drug concentration.

At 26 weeks, the investigators found proteinuria reduction—so less proteins in the urine—was greater in the ravulizumab group (40.3%) than the placebo group (10.9%). The treatment effect had been 33.1% (90% CI, 14.7% - 47.5%; P = .0012).

For patients treated with ravulizumab, proteinuria reduction was rapid and continued through week 26. Also, the glomerular filtration rate was stable. Ravulizumab had a safety profile like the placebo and was effective in treatment. Though, for adverse events, 74.4% in the ravulizumab group experienced them (n = 32) while 82.6% did in the placebo group (n = 19). The ravulizumab group experienced 1 serious adverse event (2.3%), though it was investigated as unrelated to the drug; the patient had COVID-19 which led to hospitalization.

“This analysis supports clinically meaningful efficacy of [ravulizumab] based on rapid and sustained proteinuria reduction, providing proof-of-concept for a phase 3 trial of [ravulizumab] as a potential treatment for IgAN,” the investigators wrote.

References

1. ^{Efficacy and Safety of Ravulizumab in a Phase 2 Randomized Controlled Trial in IgA Nephropathy. American Society of Nephrology. November 2, 2023. https://www.asn-online.org/education/kidneyweek/2023/program-abstract.aspx?controlId=3979029. Accessed November 15, 2023.}
2. ^{Kunzmann, K. FDA Approves Ravulizumab Injection for Pediatric PNH Patients. HCPLive. https://www.hcplive.com/view/fda-approves-ravulizumab-injection-for-pediatric-pnh-patients. Accessed November 15, 2023.}
3. ^{IgA Nephropathy. National Kidney Foundation. https://www.kidney.org/atoz/content/iganeph. Accessed November 15, 2023.}
4. ^{Proteinuria. Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-diseases/proteinuria#:~:text=Proteinuria%2C%20also%20called%20albuminuria%2C%20is,certain%20conditions%20affecting%20the%20kidneys. Accessed November 15, 2023.}