Novartis investigational oral therapy iptacopan (LNP023) shows benefit as monotherapy in treatment-naïve patients with rare and life-threatening blood disorder paroxysmal nocturnal hemoglobinuria


  • First-in-class, oral, targeted factor B inhibitor iptacopan substantially reduced both intra- and extravascular hemolysis when given as monotherapy in a Phase II study of anti-C5 naïve paroxysmal nocturnal hemoglobinuria (PNH) patients1

  • New results are promising for potential use of iptacopan as monotherapy in PNH, a rare and life-threatening blood disorder2,3; results from a previous Phase II study showed iptacopan substantially improved hematological response as add-on to standard-of-care (eculizumab)4

  • The FDA has granted Breakthrough Therapy Designation to iptacopan for PNH5; it also has received orphan drug designation for PNH from both the FDA and EMA6

  • Iptacopan is also in development for several rare renal conditions with complement system (part of the innate immune system) involvement, targeting a key driver of these diseases7,8

  • Recently presented Phase II data showed iptacopan reduced proteinuria and stabilized kidney function in IgA nephropathy (IgAN)9, and improved estimated glomerular filtration rate (eGFR) slope and stabilized kidney function in C3 glomerulopathy (C3G)10

Basel, June 11, 2021 — Novartis today announced new Phase II data for iptacopan (LNP023), an investigational oral treatment for paroxysmal nocturnal hemoglobinuria (PNH), presented at the 26th Annual Congress of the European Hematology Association (EHA). In the study (NCT03896152), treatment with 12 weeks of iptacopan monotherapy was generally well tolerated with no unexpected safety findings and resulted in rapid and durable transfusion-free improvement of hemoglobin levels in the majority of patients1.

“Currently, 20-50% of PNH patients treated with standard-of-care anti-C5 therapies remain transfusion-dependent due to persistent extravascular hemolysis, and an additional 20-40% exhibit varying degrees of residual anemia,” said lead author Professor Jun Ho Jang, Division of Hematology-Oncology, Sungkyunkwan University School of Medicine. “These results show that oral iptacopan blocks both intra- and extravascular hemolysis in patients with hemolytic PNH who have not previously been treated with an anti-C5. When considered with the findings of the previous Phase II study, these data suggest that iptacopan may provide additional benefits beyond those seen with current standard-of-care therapies, and may potentially change the PNH treatment paradigm.”

All patients completing at least 12 weeks of iptacopan treatment (n=11) achieved the primary endpoint of at least a 60% reduction in their lactate dehydrogenase (LDH) levels, a biomarker of intravascular hemolysis1. Importantly, with the exception of one patient receiving a single red blood cell (RBC) transfusion, all patients remained transfusion-free through 12 weeks of study1. Patients also showed improvement in other biomarkers of hemolysis and a marked increase in the proportion of PNH-type RBCs, indicating overall control of both intra- and extravascular hemolysis1.

No serious adverse events or thromboembolic events were reported during the 12-week treatment period and the study yielded no unexpected safety results1. Two participants discontinued iptacopan treatment before completing 12 weeks of treatment: one due to a non-serious headache, the other by physician decision due to worsening of pre-existing neutropenia1. The most common adverse events were headache (31% of patients), abdominal discomfort (15%), blood alkaline phosphatase increase (15%), cough (15%), oropharyngeal pain (15%), pyrexia (raised body temperature; 15%), and upper respiratory infection (15%)1.

“PNH is a rare and life-threatening blood disorder with often debilitating symptoms,” said John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis. “New treatment options are needed, and these positive results further strengthen the profile of iptacopan as a promising oral monotherapy. We are excited to continue to explore the potential of iptacopan as new standard-of-care treatment for PNH in the ongoing Phase III study.”

PNH, which is characterized by complement-driven hemolysis, thrombosis and impaired bone marrow function11,12, results in anemia, fatigue and other debilitating symptoms that can impact patients’ quality of life13-15. Despite treatment with current anti-C5 standard-of-care therapies, a large proportion of PNH patients remain anemic and dependent on transfusions2,3,11,13,15.

In results from the separate open-label Phase II study (NCT03439839), published in The Lancet Haematology, iptacopan improved hematological response and biomarkers of disease activity in PNH patients with active hemolysis despite treatment with the anti-C5 eculizumab4. This benefit was maintained in patients who stopped eculizumab treatment4.

About iptacopan
Iptacopan is an investigational first-in-class, orally administered targeted factor B inhibitor of the alternative complement pathway7,8. It acts upstream of the C5 terminal pathway, preventing not only intravascular but also extravascular hemolysis in PNH1. In doing so, iptacopan may have a therapeutic advantage over current standard-of-care by targeting a key part of the biology responsible for PNH7,8.

Discovered at the Novartis Institutes for BioMedical Research, iptacopan is currently in development for a number of complement-driven diseases where significant unmet needs exist, including IgAN, C3G, atypical hemolytic uremic syndrome (aHUS), and membranous nephropathy (MN), as well as the blood disorder PNH. Novartis has initiated a Phase III study of iptacopan as monotherapy in PNH.

Based on disease prevalence and the positive interim data from Phase II studies, iptacopan has received orphan drug designations from the FDA and EMA in C3G and PNH6, FDA Breakthrough Therapy Designation in PNH5, EMA PRIME designation for C3G16, and EMA orphan drug designation in IgAN17.

About the Study
NCT03896152 is a Phase II, multinational, multicenter, open-label, randomized, 2-cohort, dose-ranging trial to evaluate the efficacy, safety and pharmacokinetics/pharmacodynamics of iptacopan monotherapy in adult PNH patients with active hemolysis and no complement inhibition in the prior 3 months1. The primary objective of the study was to assess the percentage of patients with 60% reduction in LDH or LDH below upper limit of normal (ULN) up to 12 weeks of treatment1.

The study assessed four iptacopan doses in two separate cohorts with two sequential treatment periods each1. A total of 13 patients were randomized to receive either 25 mg iptacopan twice daily up to week four, rising to 100 mg iptacopan twice daily from weeks five to 12 (cohort 1; n=7), or 50 mg iptacopan twice daily up to week four, rising to 200 mg iptacopan twice daily from weeks five to 12 (cohort 2; n=6)1. Two participants discontinued iptacopan treatment before completing 12 weeks of treatment: one due to a non-serious headache, the other by physician decision due to worsening of pre-existing neutropenia1.

After the 12-week main treatment period, patients responding to iptacopan treatment had the option to enter an approximately two-year treatment extension period1.

This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 110,000 people of more than 140 nationalities work at Novartis around the world. Find out more at

Novartis is on Twitter. Sign up to follow @Novartis at
For Novartis multimedia content, please visit
For questions about the site or required registration, please contact


  1. Jang JH, et al. Iptacopan Effectively Controls Intra- And Extravascular Hemolysis And Leads To Durable Hemoglobin Increase In Patients With Treatment-Naïve PNH. Abstract presented at the 26th Annual Congress of the European Hematology Association (EHA) 2021.
  2. Risitano AM. Anti-Complement Treatment in Paroxysmal Nocturnal Hemoglobinuria: Where we Stand and Where we are Going. Transl Med UniSa 2014;8:43–52.
  3. Debureaux P, et al. Hematological Response to Eculizumab in Paroxysmal Nocturnal Hemoglobinuria: Application of a Novel Classification to Identify Unmet Clinical Needs and Future Clinical Goals. Blood 2019;134(Suppl 1):3517.
  4. Risitano AM, Röth A, Soret J, et al. Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol. Published online 2021. doi:10.1016/S2352-3026(21)00028-4..
  5. Novartis. Novartis investigational oral therapy iptacopan (LNP023) receives FDA Breakthrough Therapy Designation for PNH and Rare Pediatric Disease Designation for C3G. Available at: Accessed March 2021.
  6. Novartis. Data on file.
  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. Merle NS, et al. Complement system part II: role in immunity. Front Immunol 2015;6:257.
  9. Novartis press release. Novartis announces iptacopan met Phase II study primary endpoint in rare kidney disease IgA nephropathy (IgAN). Available at: Accessed June 2021.
  10. Novartis press release. Novartis announces new interim analysis Phase II data for iptacopan in rare kidney disease C3 glomerulopathy (C3G). Available at: Accessed June 2021.
  11. Hill A, et al. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primers 2017;3:17028.
  12. Risitano AM. Paroxysmal nocturnal hemoglobinuria and the complement system: recent insights and novel anticomplement strategies. Adv Exp Med Biol. 2013;735:155–72.
  13. Risitano AM and Rotoli B. Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents. Biologics 2008;2(2):205–222.
  14. Hill A, et al. Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization. Haematologica 2010;95(4):567–573.
  15. Schrezenmeier H, et al. Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. Haematologica 2014;99(5):922–929.
  16. Novartis. Novartis received European Medicines Agency (EMA) PRIME designation for iptacopan (LNP) in C3 glomerulopathy (C3G). Available at: Accessed March 2021.
  17. Novartis. Novartis announces European Medicines Agency (EMA) has granted orphan drug designation for iptacopan (LNP023) in IgA nephropathy (IgAN). Available at: Accessed March 2021.

# # #

Novartis Media Relations

Anja von Treskow
Novartis Strategy & Financial
+41 79 392 8697 (mobile)


Julie Masow
Novartis US External Communications
+1 862 579 8456 (mobile)
Michael Billings
Novartis Oncology Communications
+1 862 778 8656 (direct)
+1 201 400 1854 (mobile)


Phil McNamara
Novartis Cardio-Renal- Metabolic Communications
+1 862 778 0218 (direct)
+1 862 274 5255 (mobile)

Novartis Investor Relations
Central investor relations line: +41 61 324 7944

Central North America 
Samir Shah+41 61 324 7944Sloan Simpson+1 862 778 5052
Thomas Hungerbuehler+41 61 324 8425  
Isabella Zinck+41 61 324 7188  


Media release (PDF).pdf