The FDA has approved the twice-daily oral capsule iptacopan (Fabhalta; Novartis) for the treatment of adults with complement 3 glomerulopathy (C3G) to reduce proteinuria.1
C3G is a rare disease, affecting an estimated 2 to 3 of every 1 million people, that causes inflammation and damage to the kidney glomeruli, which are responsible for filtering blood and producing urine. In C3G, the complement system becomes abnormally activated. Complement products can become lodged in the glomeruli, causing them to become leaky and harming their ability to filter blood. Waste products and toxins then build up in the blood, which decreases the kidneys’ ability to balance salts and minerals, decreases urine production, and causes continued kidney damage.
The efficacy and safety of iptacopan were evaluated in a randomized, double-blind, placebo-controlled study in 74 adults with biopsy-confirmed C3G who had a urine protein-to-creatinine ratio (UPCR) ≥1 g/g and an estimated glomerular filtration rate ≥30 mL/min/1.73 m2. Patients were randomly assigned to receive either iptacopan or placebo for 6 months, followed by a 6-month open-label treatment period in which all patients received iptacopan.
The primary efficacy end point assessed the percent change in proteinuria (UPCR sampled from a 24-hour urine collection) after 6 months of treatment. At 6 months, there was a 35% reduction from baseline in 24-hour UPCR in the study treatment group compared with placebo.
In patients initially randomized to iptacopan, the reduction in 24-hour UPCR seen at 6 months was maintained at 12 months. In patients who switched from placebo to iptacopan, the magnitude of the reduction in 24-hour UPCR from 6 to 12 months was similar to the reduction seen in patients initially randomized to the study treatment.
Iptacopan increases the risk of serious and life-threatening infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. Patients should complete or update vaccination for encapsulated bacteria at least 2 weeks before the first dose of iptacopan, unless the risks of delaying treatment outweigh the risks of developing a serious infection. Healthcare providers should monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.
The most common adverse reactions (reported in at least 10% of patients) to iptacopan were nasopharyngitis (common cold) and viral infections.
The FDA first approved iptacopan in 2023 for the treatment of adults with paroxysmal nocturnal hemoglobinuria. It is also approved under accelerated approval for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy at risk of rapid disease progression.
Reference
- Food and Drug Administration. FDA approves first treatment for adults with complement 3 glomerulopathy, a rare kidney disease, to reduce proteinuria [press release]. March 20, 2025. Accessed April 14, 2025. www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-adults-complement-3-glomerulopathy-rare-kidney-disease-reduce