Novartis reports positive data from the Phase III APPLAUSE study which reinforces the potential of iptacopan

Novartis announced Monday positive top-line results from the pre-specified interim analysis of the Phase III APPLAUSE-IgAN study (NCT04578834) at 9 months.

Iptacopan, an investigational factor B inhibitor targeting the alternative complement pathway, demonstrated superiority versus placebo in proteinuria (protein in urine) reduction and provided a clinically meaningful and highly statistically significant proteinuria reduction on top of supportive care in patients with IgA nephropathy (IgAN), a complement-mediated disease, Novartis said in the press release..

In the study, the safety profile of iptacopan (200 mg twice daily) was consistent with previously reported data. The study continues in a double-blind fashion to evaluate iptacopan’s ability to slow IgAN progression by measuring estimated glomerular filtration rate (eGFR) slope over 24 months – the primary endpoint at the study end with topline results expected in 2025, Novartis said in the press release..

Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis, said: “These positive data from the Phase III APPLAUSE study reinforce the potential of iptacopan to provide clinically meaningful benefit to patients with IgAN, a debilitating disease that affects mostly young adults.”

It is estimated that approximately 25 people per million worldwide are newly diagnosed with IgAN each year. Up to 30% of people who have IgAN with persistent higher levels of proteinuria (≥1 g/day) may progress to kidney failure within 10 years, Novartis said in the press release.

There is a need for effective, targeted therapies for IgAN that slow or prevent progression to kidney failure. Although current supportive care and treatment can help, they don’t address a key pathogenic step in the progression of IgAN: activation of the complement system, Novartis said in the press release.

Discovered and developed by Novartis, iptacopan aims to address IgAN and other complement-mediated diseases by inhibiting factor B, a protease essential to the alternative complement pathway.

Iptacopan is under review by regulators following positive Phase III results in paroxysmal nocturnal hemoglobinuria (APPLY-PNH [NCT04558918] and APPOINT-PNH [NCT04558918]). Iptacopan is also being investigated in Phase III studies for C3 glomerulopathy (APPEAR-C3G [NCT04817618]), atypical hemolytic uremic syndrome (APPELHUS [NCT04889430]) and immune complex membranoproliferative glomerulonephritis (APPARENT [NCT05755386]). With the recent acquisition of Chinook Therapeutics, the Novartis renal portfolio expands with two additional late-stage medicines in development for IgAN, complementing the existing pipeline.

Novartis intends to submit for possible accelerated approval with the FDA in 2024.