Novartis Announces Iptacopan Met Primary Endpoint in Phase 2 Trial for IgA Nephropathy

Compiled & Translated | newborn

On June 6, Novartis announced primary endpoint data from a Phase 2 study of iptacopan, the most advanced asset in its nephrology pipeline. The results showed that patients with IgA nephropathy (IgAN) treated with iptacopan experienced a clinically meaningful reduction in urinary protein (proteinuria), a key predictive risk factor for kidney disease progression. Additionally, patients with IgAN receiving iptacopan also demonstrated a trend toward stabilized kidney function.

In this study (NCT03373461), 112 patients with IgAN were randomized to receive placebo or different doses of iptacopan. The primary endpoint was the dose-response effect of iptacopan versus placebo in reducing proteinuria at 90 days of treatment (measured by the 24-hour urine protein-to-creatinine ratio [UPCR 24h]).

According to the Novartis announcement, this is the first study to report the efficacy and safety of selectively inhibiting the alternative complement pathway in IgAN. The results showed that the study met its primary endpoint: at Day 90 of treatment, iptacopan demonstrated a statistically significant (p=0.038) dose-response effect in reducing proteinuria compared with placebo. Specifically, compared with placebo, treatment with the highest dose of iptacopan (200 mg twice daily) was projected to reduce proteinuria by 23% at Day 90.

Additionally, based on the estimated glomerular filtration rate (eGFR), iptacopan also demonstrated a trend toward stabilizing renal function. In this study, iptacopan was safe and well tolerated.

Chemical structure of iptacopan (Image source: medchemexpress.cn)

IgA nephropathy (IgAN) is classified as a complement-driven renal disease (CDRD). These disorders are believed to be partially caused by the overactivation of the alternative complement pathway, which triggers an inflammatory response and leads to renal injury. CDRD predominantly affects younger individuals, frequently progressing to renal failure that necessitates dialysis or kidney transplantation, and may result in premature death.

IgA nephropathy (IgAN) is a rare progressive kidney disease. Patients with persistent proteinuria ≥1 g/day are at a higher risk of disease progression, with approximately 30% progressing to renal failure within 10 years. Currently, there are no approved treatments specifically for IgAN. While corticosteroids are commonly used in clinical practice, data regarding their efficacy are inconsistent, and these agents are associated with well-known adverse effects, some of which can be severe. There is currently an urgent need for effective and well-tolerated targeted therapies to delay the progression of IgAN.

iptacopan treats this category of kidney diseases by targeting key drivers of CDRD. iptacopan is a first-in-class, oral Factor B inhibitor, and Factor B is a key enzyme in the alternative complement pathway. iptacopan has the potential to become the first targeted therapy capable of delaying the progression of IgAN to dialysis. In addition to IgAN, Novartis is also developing iptacopan for the treatment of various CDRDs, including C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS), membranous nephropathy (MN), and paroxysmal nocturnal hemoglobinuria (PNH).

Although Novartis has a 35-year history in kidney transplant therapy, iptacopan is the first drug in the company’s nephrology pipeline designed to address CDRD, aiming to transform the treatment paradigm by targeting the key drivers of this rare disease and extending dialysis-free survival for patients with CDRD.

Source: Novartis announces iptacopan met Phase II study primary endpoint in rare kidney disease IgA nephropathy (IgAN)