Novartis’ Oral Factor B Inhibitor Iptacopan Receives FDA Breakthrough Therapy Designation for PNH and Rare Pediatric Disease Designation for C3G

December 17, 2020 /BioonBIOON/ --Novartis(Novartis) recently announced that the U.S. Food and Drug Administration (FDA) has been granted Breakthrough Therapy designation for iptacopan (LNP023) in the treatment of paroxysmal nocturnal hemoglobinuria (PNH), and Rare Pediatric Disease (RPD) designation for the treatment of C3 glomerulopathy (C3G). In October this year, the European Medicines Agency (EMA) granted Priority Medicines (PRIME) designation to iptacopan for the treatment of C3G.

Iptacopan is a first-in-class, oral, potent, selective, small-molecule, reversible Factor B inhibitor. Factor B is a key serine protease in the alternative pathway of the complement system. In addition to PNH and C3G, iptacopan is currently being developed for the treatment of other kidney diseases involving the complement system with significant unmet medical needs, including IgA nephropathy (IgAN) and atypical hemolyticUremiasyndrome (aHUS), membranous nephropathy (MN).

NovartisIt is expected that the first indication application will be submitted to the U.S. FDA in 2023.In many complement-driven diseases, iptacopan has the potential to become the first complement pathway inhibitor that delays disease progression.Based on the disease prevalence and positive interim data from Phase 2 studies, iptacopan was also approved by the U.S.FDAand orphan drug designation (ODD) granted by the EU EMA for the treatment of C3G and PNH, as well as by the EMA for the treatment of IgAN.

Chemical Structure of Iptacopan (Image source: medchemexpress.cn)

Breakthrough Therapy Designation (BTD) is a new drug review pathway established by the FDA in 2012, aimed at accelerating the development and review of new drugs intended to treat serious or life-threatening diseases, where preliminary clinical evidence indicates that the drug demonstrates significant improvement over existing therapies on one or more clinically meaningful endpoints. Drugs granted BTD can receive, during their development, includingFDACloser guidance, including from senior officials, to ensure that new treatment options are made available to patients in the shortest possible time.

FDABTD Granted for Iptacopan in the Treatment of PNH, Based on Positive Interim Results from Two Ongoing Phase II Studies. Data Showed that Iptacopan Was Effective in Patients Who RemainedAnemiaSignificant therapeutic benefits were observed in patients with PNH who are transfusion-dependent, as well as in treatment-naïve (anti-C5 naïve) patients with PNH receiving monotherapy who had not previously received anti-C5 therapy.

PNH is a rare, life-threatening blood disorder characterized by complement-mediated hemolysis, thrombosis, and impaired bone marrow function, leading to anemia, fatigue, and other debilitating symptoms that may affect patients’ quality of life. Although the current standard of care is anti-C5 therapy with Soliris (eculizumab) or Ultomiris (ravulizumab), a significant proportion of PNH patients remain anemic and transfusion-dependent.

Kidney (Image source: parashospitals.com)

FDARare Pediatric Disease (RPD) designation targets severe or life-threatening diseases that primarily affect individuals under 18 years of age and have a prevalence of fewer than 200,000 affected individuals.C3G is an extremely rare and severe primary glomerulonephritis characterized by dysregulation of complement regulation.

C3G is typically seen in adolescents and young adultsDiagnosisthis disease has a very poor prognosis, with approximately 50% of patients progressing to end-stage renal disease (ESRD) within 10 years, and 50-70% experiencing recurrence after kidney transplantation. Worldwide, the annual incidence of C3G is 1-2 per million, with approximately 10,000 cases in the United States, 10,500 in Europe, 3,200 in Japan, and 32,000 in China.

The positive Phase II data for iptacopan in the treatment of PNH were presented at the European Society for Blood and Marrow Transplantation (EBMT) Congress this August, and the interim analysis results from the Phase II study in C3G were presented at the virtual annual meeting of the American Society of Nephrology (ASN) held this October.NovartisPhase III trials have been planned to be initiated across multiple indicationsClinical Trial(Bioon.com)

Original source: Novartis investigational oral therapy iptacopan (LNP023) receivesFDA Breakthrough Therapy Designation for PNH and Rare Pediatric Disease Designation for C3G