?Orphan drug designation is reserved for medicines treating rare, life-threatening or chronically debilitating diseases
?IgA nephropathy (IgAN), while rare, is the most common form of glomerulonephritis, affecting mostly young adults with no approved treatment option and significant risk to progress to end stage renal disease (ESRD) 1,2,3
?Iptacopan (LNP023) is a potential first-in-class, oral, potent and selective factor B inhibitor of the alternative complement pathway, which is involved in the underlying pathophysiology of IgA nephropathy4
?Iptacopan is in parallel development for a number of renal conditions, including IgAN, C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS), and membranous nephropathy (iMN) as well as in paroxysmal nocturnal hemoglobinuria (PNH), a hematological disease.

Basel, October 23, 2020 — Novartis today announced that the European Medicines Agency (EMA) has granted an orphan drug designation for iptacopan (LNP023) in IgA nephropathy (IgAN), following a recommendation from the Committee for Orphan Medicinal Products (COMP).

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 currently approved method of diagnosis, prevention or treatment or with significant benefit to those affected by the disease.

IgAN is the most common form of primary glomerulonephritis – an inflammatory kidney disease where abnormal IgA antibody is formed, which results in immune complex deposition in the glomerular mesangium, leading to deteriorating kidney function.1,2

In patients with IgAN, proteinuria is recognized as an independent risk factor of poor prognosis. Around 30% of patients with persistent proteinuria progress to end stage renal disease (ESRD) within 10 years5. No approved targeted therapy is available.

ESRD requires dialysis or kidney transplant and is associated with significant risk of complications, considerable impact on quality of life as well as an increased risk of premature death.5

About iptacopan
Iptacopan (LNP023) is a first-in-class oral, small-molecule, selective inhibitor of factor B, a key serine protease of the alternative pathway of the complement cascade mediating inflammatory responses.6-8

In addition to IgAN, iptacopan is in parallel development for a number of other renal conditions with complement system involvement where significant unmet needs exist, including C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS), and membranous nephropathy (iMN). Novartis is also investigating iptacopan in paroxysmal nocturnal hemoglobinuria (PNH), a hematological disease.

Positive Phase II data in PNH were presented at the European Society for Blood and Marrow Transplantation (EBMT) congress in August9, and Phase II interim analysis results in C3G will be presented at the upcoming virtual 2020 Annual Meeting of the American Society of Nephrology (ASN). Novartis is planning to initiate Phase III studies in several indications.

Iptacopan has the potential to become the first alternative complement pathway inhibitor to slow disease progression in a number of complement-driven diseases. Based on disease prevalence and the interim data from Phase II studies, iptacopan has also received orphan drug designations from the FDA and EMA in C3G and PNH10 as well as EMA PRIME designation for C3G.11

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References
1. Rodrigues JC et al. IgA Nephropathy. Clin J Am Soc Nephrol. 2017 Apr 3; 12(4): 677–686.
2. Rizk DV et al. The Emerging Role of Complement Proteins as a Target for Therapy of IgA Nephropathy. Front Immunol. 2019; 10: 504.
3. Xie, J et al. Predicting Progression of IgA Nephropathy: New Clinical Progression Risk ScorePLoS One. 2012; 7(6): e38904.
4. Thurman, J and al. Complement and Glomerulonephritis. Clin J Am Soc Nephrol 11: 1856-1866.
5. Reich HN et al. Remission of Proteinuria Improves Prognosis in IgA Nephropathy Am Soc Nephrol 18: 3177–3183, 2007
6. Merle NS, et al. Complement System Part II: Role in Immunity. Front Immunol. 2015;6:257.
7. Schubart A, et al. Small-molecule factor B inhibitor for the treatment of complement-mediated diseases. Proc Natl Acad Sci U S A. 2019;116(16):7926–7931.
8. Harris CL. Expanding horizons in complement drug discovery: challenges and emerging strategies. Semin Immunopathol. 2018;40(1):125–140.
9. Novartis. Novartis announces positive results from Phase II study of LNP023 in patients with paroxysmal nocturnal hemoglobinuria (PNH). Available at: https://www.novartis.com/news/media-releases/novartis-announces-positive-results-from-phase-ii-study-lnp023-patients-paroxysmal-nocturnal-hemoglobinuria-pnh. Accessed September 2020.
10. Novartis Data on File
11. Novartis. Novartis received European Medicines Agency (EMA) PRIME designation for iptacopan (LNP) in C3 glomerulopathy (C3G). Available at: https://www.novartis.com/news/media-releases/novartis-received-european-medicines-agency-ema-prime-designation-iptacopan-lnp-c3-glomerulopathy-c3g. Accessed October 2020.

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