Novartis Reports Positive Interim Phase 2 Results for First-in-Class Oral Complement Inhibitor Iptacopan in C3 Glomerulopathy

Novartis Announces Positive Interim Phase 2 Clinical Results for Iptacopan (LNP023), a Potential First-in-Class Oral Therapy Targeting the Complement Pathway, in Patients with C3 Glomerulopathy (C3G); Iptacopan Significantly Reduces Proteinuria Levels in C3G Patients

C3 glomerulopathy (C3G) is a severe form of primary glomerulonephritis characterized by dysregulation of the complement signaling pathway. The disease carries a poor prognosis, with approximately 50% of patients progressing to end-stage renal disease (ESRD) within 10 years, and 50–70% experiencing disease recurrence after kidney transplantation. Currently, there are no approved therapies specifically targeting the underlying complement dysregulation in patients with C3G. The existing standard of care consists of non-specific immunosuppressants, which offer limited clinical benefit. Therefore, new therapeutic approaches are needed to address disease manifestations and slow the progression of C3G.

Iptacopan (LNP023) is a first-in-class, oral, small-molecule, reversible inhibitor of complement factor B, a key serine protease in the alternative pathway of the complement cascade. In addition to C3 glomerulopathy (C3G), iptacopan is being developed for other complement-mediated diseases with significant unmet medical needs, including IgA nephropathy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and membranous nephropathy. Iptacopan has the potential to become the first alternative complement pathway inhibitor to slow disease progression in many complement-driven disorders. Last year, Novartis listed it as one of 25 potential blockbuster therapies during its R&D Day event.

Interim data from this open-label Phase 2 clinical trial showed that, in 12 patients with C3 glomerulopathy (C3G), iptacopan significantly reduced proteinuria by 49% compared with baseline (P=0.0005). Iptacopan potently inhibited alternative complement pathway activity and improved plasma C3 levels. Furthermore, iptacopan stabilized renal function as assessed by estimated glomerular filtration rate (eGFR) at Week 12 of treatment. This effect was maintained in the seven patients who had received six months of treatment after enrolling in the long-term extension study.

References:

[1] Novartis presents promising interim Phase II data of potential first-in-class oral therapy iptacopan (LNP023) in rare renal disease C3 glomerulopathy (C3G). Retrieved October 26, 2020, from https://www.novartis.com/news/media-releases/novartis-presents-promising-interim-phase-ii-data-potential-first-class-oral-therapy-iptacopan-lnp023-rare-renal-disease-c3-glomerulopathy-c3g

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