Sibeprenlimab Designated Breakthrough Therapy for IgA Nephropathy

The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to sibeprenlimab for the treatment of immunoglobulin A nephropathy (IgAN).

Sibeprenlimab is a humanized IgG2 monoclonal antibody that reduces the production of galactose deficient IgA1 by binding to and neutralizing a proliferation-inducing ligand (APRIL). The designation was granted based on data from the phase 2 ENVISION trial (ClinicalTrials.gov Identifier: NCT04287985), which included adults with biopsy-confirmed IgAN at high risk of progression.

Study participants (N=155) were randomly assigned to receive monthly injections of sibeprenlimab  (2, 4, or 8mg/kg) or placebo for 12 months. The primary endpoint was the change from baseline in 24-hour urine protein-to-creatinine ratio (uPCR). 

Findings showed treatment with sibeprenlimab significantly reduced proteinuria compared with placebo at 12 months. Geometric mean ratio reduction in 24-hour uPCR from baseline was 47.2% with the 2mg/kg dose, 58.8% with the 4mg/kg dose, and 62% with the 8mg/kg dose vs 20% with placebo.

At 12 months, annual eGFR changes (secondary endpoint) were -2.7, +0.2, and -1.5mL/1.73m² for the sibeprenlimab 2, 4, and 8mg/kg doses, respectively, compared with -7.4mL/1.73m² with placebo. The incidence of adverse events was similar in the  sibeprenlimab and placebo groups.

“We are encouraged by the FDA’s decision to grant Breakthrough Therapy status for the sibeprenlimab program,” said John Kraus, MD, PhD, executive vice president and chief medical officer at Otsuka. “This is an important milestone that recognizes the potential value that this investigational candidate may have in the future for people living with one of the most common causes of kidney failure.”