Novartis Announces Iptacopan Met Primary Endpoint in Rare Kidney Disease IgA Nephropathy

Novartis announced Phase II primary endpoint data showing investigational iptacopan (LNP023) – a first-in-class, oral, targeted factor B inhibitor – reduced protein in the urine (proteinuria), an increasingly recognized surrogate marker correlating with progression to kidney failure, and showed promise in stabilizing kidney function in patients with IgA nephropathy (IgAN).

In the Phase II study (NCT03373461), patients (n=112) with IgAN were randomized to placebo or different doses of iptacopan. The primary endpoint was met with a statistically significant (p=0.038) dose-response effect on reduction in proteinuria (as measured by 24-hour urinary protein to creatine ratio [UPCR 24h]) with iptacopan vs. placebo, at 90 days. At the highest dose of 200mg twice daily a 23% reduction in proteinuria was predicted, compared with placebo, at 90 days.

“IgAN is a devastating disease with no currently approved treatments. These efficacy data, seen after 90 days of treatment, along with the safety profile, offer hope that inhibition of the alternative complement pathway with iptacopan may be an effective way to delay IgAN disease progression,” said study lead author Jonathan Barratt, Professor of Renal Medicine, University of Leicester and nephrology consultant, Leicester General Hospital.

Iptacopan also demonstrated a trend towards stabilizing kidney function, as assessed by estimated glomerular filtration rate (eGFR): a key measure of kidney clearance function that estimates the rate of blood passing through and being filtered by the kidneys. Additionally, iptacopan showed a favorable safety and tolerability profile.

Iptacopan is the most advanced asset in the company’s nephrology pipeline and targets the alternative complement pathway, a key driver of complement-driven renal diseases (CDRDs). Novartis has plans to initiate additional Phase III studies in other renal indications.

Iptacopan is also in development for a life-threatening blood disorder, paroxysmal nocturnal hemoglobinuria (PNH).