Novartis released promising interim Phase II data of iptacopan in C3 glomerulopathy (C3G). The analysis was presented at the virtual American Society of Nephrology (ASN) 2020 Annual Meeting.
Novartis CEO Vasant Narasimhan pictured above. Photo courtesy of Novartis.
Novartis released promising interim Phase II data of iptacopan in C3 glomerulopathy (C3G). The analysis was presented at the virtual American Society of Nephrology (ASN) 2020 Annual Meeting.
C3G is an ultra-rare and severe type of primary glomerulonephritis. It is marked by complement dysregulation, which is a major component of the immune system. It occurs in about 1-2 per million people worldwide and about 10,000 in the U.S. It is most commonly diagnosed in adolescents and young adults and has a poor prognosis, with about half of patients progressing to end-stage renal disease (ESRD) within 10 years and 50-70% experience recurrence after a kidney transplant.
Iptacopan is a first-in-class oral, small molecule that inhibits factor B. Factor B is a key serine protease of the alternative pathway of the complement cascade. In addition to C3G, the drug is in parallel development for a range of renal conditions associated with complement system dysregulation, including IgA nephropathy, atypical hemolytic uremic syndrome and membranous nephropathy. It is also being evaluated in paroxysmal nocturnal hemoglobinuria (PNH).
In the interim data analysis, after 12 weeks iptacopan significantly decreased proteinuria (protein in the urine) by 49% compared to baseline values. It was measured by 24-hour urine protein/creatinine ratio (UPCR) evaluation in 12 patients with C3G. The drug strongly inhibited alternative complement pathway activity and improved plasma C3 levels. It also stabilized renal function.
“Proteinuria indicates the presence of inflammation in the kidney,” said Edwin Wong, the study’s lead investigator, Consultant Nephrologist at the National Renal Complement Therapeutics Centre, Newcastle upon Tyne NHS Foundation Trust, Newcastle University. “Results from this study demonstrate that iptacopan significantly reduces proteinuria in patients with C3G. This data also highlights iptacopan’s ability to strongly and specifically inhibit the alternative complement pathway, targeting the underlying cause of this disease and potentially providing a much-needed treatment option for C3G patients who have significant unmet needs.”
The drug recently received Orphan Drug Status by the European Medicines Agency (EMA) after a recommendation from the organization’s Committee for Orphan Medicinal Products (COMP) for IgAN. IgAN, although a rare disorder, is the most common form of primary glomerulonephritis, an inflammatory kidney disease.
Novartis stated, “Orphan drug designation is granted to medicines that treat, prevent or diagnose a life-threatening or chronically debilitating rare disease, with a prevalence in the EU of below 5 in 10,000, and with either no current approved method of diagnosis, prevention or treatment or with significant benefit to those affected by the disease.”
In IgAN, an abnormal type of IgA (immunoglobulin A) antibody develops. This leads to immune complex deposits in the glomerular mesangium, a network of small blood vessels at the beginning of a kidney nephron. The network of small blood vessels is called a tuft and it is structurally supported by the mesangium, which is the space between the blood vessels. It leads to loss of kidney function.
Proteinuria in IgAN is an independent risk factor of poor prognosis. About 30% of patients with persistent protein in the urine end up with ESRD within 10 years.
John Tsai, head of Global Drug Development and chief medical officer of Novartis, said, “Iptacopan is the most advanced asset in our nephrology pipeline. These data demonstrate that it has the potential to improve the lives of patients with C3G.”
