Novartis First Complement Inhibitor Wins Full Approval in IgA Nephropathy

 The FDA fully approved iptacopan (Fabhalta) to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) at risk of disease progression, drugmaker Novartis announced on Friday.

The complement inhibitor's conversion from accelerated to traditional approval hinged on findings from APPLAUSE-IgAN. The phase III study demonstrated a 48% reduction in the rate of estimated glomerular filtration rate (eGFR) decline compared with placebo over 24 months. Patients treated with iptacopan had an annualized mean change from baseline in eGFR of -3 mL/min/1.73 m² per year versus -5.7 mL/min/1.73 m² per year for those on placebo.

"The ability to significantly slow kidney function decline is a critical treatment goal," said investigator Dana Rizk, MD, of the University of Alabama at Birmingham, in the company's press release. "This approval of Fabhalta reinforces the importance of targeting underlying disease mechanisms, including complement activation, in treating IgAN to help preserve kidney health."

The treatment effect in the trial was consistent across all prespecified subgroups, indicating that iptacopan can mitigate kidney function decline in a broad population of patients with IgAN.

Iptacopan is a first-in-class Factor B inhibitor designed to selectively target the alternative complement pathway -- one of several key drivers of glomerular inflammation and kidney damage in IgAN. The drug also holds indications for paroxysmal nocturnal hemoglobinuria and complement 3 glomerulopathy.

As one of the most common autoimmune kidney diseases, IgAN is diagnosed in an estimated 2.5 per 100,000 adults worldwide each year. Approximately half of these patients progress to kidney failure or death within 10 to 20 years of diagnosis, which typically occurs in young adulthood.

Patients with the disease develop kidney damage due to an abnormal accumulation of IgA antibodies. This buildup damages the glomeruli, leading to inflammation, proteinuria, and potentially end-stage renal disease.

Iptacopan is the third IgAN therapy to receive traditional FDA approval, joining the corticosteroid budesonide (Tarpeyo) and the endothelin and angiotensin II receptor antagonist sparsentan (Filspari), following their own accelerated approvals.

A handful of other IgAN agents -- the endothelin receptor antagonist atrasentan (Vanrafia), the activity of a proliferation-inducing ligand (APRIL) blocker sibeprenlimab (Voyxact), and the dual APRIL/B-cell activating factor (BAFF) blocker atacicept (Trutakna) -- have also secured accelerated approvals based on proteinuria reduction, but the regulatory pathway requires confirmation of clinical benefit.

The safety profile of iptacopan remained consistent with previously reported data, with abdominal pain, dizziness, and nausea reported as the most common adverse events.

The drug carries a boxed warning for an increased risk of infections caused by encapsulated bacteria, and is only available through a risk evaluation and mitigation strategy program requiring appropriate vaccinations prior to treatment.

https://www.medpagetoday.com/nephrology/generalnephrology/122246