Novartis Fabhalta® shows statistically significant and clinically meaningful improvements in hemoglobin in new population of patients with PNH

“Today, some patients living with PNH have unmet needs not addressed by eculizumab or ravulizumab,” said Austin Kulasekararaj, Consultant Hematologist, Kings College Hospital and Kings College London. “The positive results from APPULSE-PNH reinforce that Fabhalta can provide clinically meaningful improvements in hemoglobin among patients with higher baseline hemoglobin levels than those enrolled in previous trials, while offering an oral monotherapy for patients.”

No patients required transfusion during the study, and the vast majority (92.7%) achieved Hb ≥12g/dL, reaching normal or near-normal levels¹. Patients treated with Fabhalta also reported clinically meaningful improvements in fatigue (as measured by FACIT-Fatigue score) through Day 168, reaching absolute levels similar to those reported in the general population^1,3,4.

Furthermore, patients treated with Fabhalta maintained intravascular hemolysis control and resolved extravascular hemolysis control, as demonstrated by lactate dehydrogenase levels (<1.5 upper limit of normal) and a reduction in absolute reticulocyte count¹.

“Novartis is dedicated to advancing research and innovation that can transform care and significantly improve the lives of people living with PNH and those who support them,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “New data from APPULSE-PNH, combined with findings from the Phase III roll-over extension of the APPLY-PNH and APPOINT-PNH studies, reinforce the efficacy and safety profile of Fabhalta in delivering real benefits to patients. Fabhalta is the first and only oral monotherapy currently available for the treatment of adults with PNH, regardless of previous treatment experience."

Alongside APPULSE-PNH, longer-term data from patients initially included in the APPLY-PNH and APPOINT-PNH Phase III studies will be presented at EHA¹. In APPULSE-PNH and the Phase III roll-over extension study of the APPLY-PNH and APPOINT-PNH studies, Fabhalta was well-tolerated with no new safety signals, consistent with previously reported data^1,5.

About paroxysmal nocturnal hemoglobinuria (PNH)
PNH is a rare, chronic and serious complement-mediated blood disorder⁶. People with PNH have an acquired mutation in some of their hematopoietic stem cells (which are located in the bone marrow and can grow and develop into red blood cells [RBCs], white blood cells and platelets) that causes them to produce RBCs that are susceptible to premature destruction by the complement system^6,7. This leads to intravascular hemolysis (destruction of RBCs within blood vessels) and extravascular hemolysis (destruction of RBCs mostly in the spleen and liver), which cause anemia (low levels of circulating RBCs), thrombosis (formation of blood clots), fatigue and other debilitating symptoms^6,7.
   
It is estimated that approximately 10-20 people per million worldwide live with PNH⁶. Although PNH can develop at any age, it is often diagnosed in people between 30-40 years old^8,9.

PNH has a significant unmet need not addressed by anti-C5 therapies (eculizumab or ravulizumab). Anti-C5 therapies (eculizumab or ravulizumab) are commonly administered every 2-8 weeks as intravenous infusions, and treatment visits (including journey, waiting, infusion and recovery time) can take approximately 4 to 5 hours¹⁰. Despite treatment with anti-C5 therapies, a large proportion of people with PNH remain anemic, and some dependent on blood transfusions^7,11-16.

About APPULSE-PNH
APPULSE-PNH (NCT05630001) is a Phase IIIB, multinational, multicenter, single-arm, open-label study to evaluate the efficacy and safety of twice-daily oral Fabhalta^® (iptacopan) monotherapy (200mg) in adults with PNH who were switched from anti-C5 therapies (eculizumab or ravulizumab)². The trial enrolled 52 participants who received Fabhalta for 24 weeks².

Participants enrolled were required to be on a stable regimen with anti-C5 therapies (eculizumab or ravulizumab) for at least 6 months prior to screening with average hemoglobin (Hb) ≥10g/dL and no red blood cell transfusions in this period^2,17. The primary endpoint is change from baseline Hb levels after 24 weeks of treatment with Fabhalta^2,17.

About APPLY-PNH
APPLY-PNH (NCT04558918) is a Phase III, randomized, multinational, multicenter, active-comparator controlled, open-label trial to evaluate the efficacy and safety of twice-daily, oral Fabhalta^® (iptacopan) monotherapy (200mg) for the treatment of PNH by demonstrating the superiority of Fabhalta compared to anti-C5 therapies (eculizumab or ravulizumab) in adult patients presenting with residual anemia (Hb <10 g/dl) despite a stable regimen of anti-C5 treatment in the last six months prior to randomization^5,18.

About APPOINT-PNH 
APPOINT-PNH (NCT04820530) is a Phase III, multinational, multicenter, open-label, single-arm study to evaluate the efficacy and safety of twice-daily, oral Fabhalta^® (iptacopan) monotherapy (200mg) in adult PNH patients who are naïve to complement inhibitor therapy, including anti-C5 therapies (eculizumab or ravulizumab)^19,20.

About Fabhalta® (iptacopan) 
Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative complement pathway^21,22.

Discovered at Novartis, Fabhalta received US Food and Drug Administration (FDA) and European Commission (EC) approval in December 2023 and May 2024 respectively for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH) and accelerated approval in the US in August 2024 for the reduction of proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression (generally UPCR ≥1.5 g/g 1.5 g/g)^1,23,24. In 2025, Fabhalta received FDA and EC approval for the treatment of adults with C3 glomerulopathy (C3G) to reduce proteinuria, making it the first and only treatment approved for this condition^25-31.

Fabhalta is being studied in a broad range of rare kidney diseases, including atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN). Studies are ongoing to evaluate the safety and efficacy profiles in these investigational indications and support potential regulatory submissions^32-35.

Disclaimer
This media update 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,” “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 media update, 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 media update 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; 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 media update as of this date and does not undertake any obligation to update any forward-looking statements contained in this media update as a result of new information, future events or otherwise.

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References

1. Novartis. Data on file.
2. Clinicaltrials.gov. NCT05630001. Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan. (APPULSE). Available from: https://clinicaltrials.gov/study/NCT05630001 Accessed May, 2025.
3. Montan I, Löwe B, Cella D, Mehnert A, Hinz A. General Population Norms for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale. Value Health. 2018;21(11):1313-1321. doi:10.1016/j.jval.2018.03.013
4. Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002;94(2):528-538. doi:10.1002/cncr.10245
5. Peffault de Latour R, Röth A, Kulasekararaj AG, et al. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2024;390(11):994-1008. doi:10.1056/NEJMoa2308695
6. Cançado RD, Araújo ADS, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematol Transfus Cell Ther. 2021;43(3):341-348.
7. Dingli D, Matos JE, Lehrhaupt K, et al. The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey. Ann Hematol. 2022;101(2):251-263.
8. Hill A, DeZern AE, Kinoshita T, Brodsky RA. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primers. 2017;3:17028.
9. Röth A, Maciejewski J, Nishimura JI, Jain D, Weitz JI. Screening and diagnostic clinical algorithm for paroxysmal nocturnal hemoglobinuria: Expert consensus. Eur J Haematol. 2018;101(1):3-11.
10. Levy AR, Dysart L, Patel Y, et al. Comparison of Lost Productivity Due to Eculizumab and Ravulizumab Treatments for Paroxysmal Nocturnal Hemoglobinuria in France, Germany, Italy, Russia, Spain, the United Kingdom, and the United States. Blood. 2019;134(Supplement_1):4803.
11. McKinley CE, Richards SJ, Munir T, et al. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130(Supplement 1):3471.
12. Risitano AM, Marotta S, Ricci P, et al. Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT. Front Immunol. 2019;10:1157.
13. Shammo J, Kim J, Georget M, et al. P796: Hospitalization in patients with paroxysmal nocturnal hemoglobinuria: a retrospective analysis of observational study data from the United States. Hemasphere. 2023;7(Suppl):e22585a2.
14. Debureaux PE, Kulasekararaj AG, Cacace F, et al. Categorizing hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: a multicenter real-life study. Bone Marrow Transplant. 2021;56(10):2600-2602.
15. Schrezenmeier H, Kulasekararaj A, Mitchell L, et al. One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naïve to complement inhibitor therapy: open-label extension of a randomized study. Ther Adv Hematol. 2020;11:2040620720966137.
16. Young NS, Meyers G, Schrezenmeier H, Hillmen P, Hill A. The management of paroxysmal nocturnal hemoglobinuria: recent advances in diagnosis and treatment and new hope for patients. Semin Hematol. 2009;46(1 Suppl 1):S1-S16.
17. Risitano AM, Araten DJ, Kuter D, et al. Pb2063: APPULSE-PNH: A phase IIIB trial to evaluate the efficacy and safety of switching to iptacopan in patients with paroxysmal nocturnal hemoglobinuria (PNH) on anti-c5 therapy with hemoglobin >10g/dl. Hemasphere. 2023;7(Suppl):e08587b7.
18. Clinicaltrials.gov. NCT04558918. Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment (APPLY-PNH). Available from: https://clinicaltrials.gov/study/NCT04558918 Accessed May, 2025.
19. Risitano AM, Han B, Ueda Y, et al. Oral Complement Factor B Inhibitor Iptacopan Monotherapy Improves Hemoglobin to Normal/Near-Normal Levels in Paroxysmal Nocturnal Hemoglobinuria Patients Naïve to Complement Inhibitors: Phase III APPOINT-PNH Trial. Presented at: 49th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT); April 23-36, 2023; Paris, France.
20. Clinicaltrials.gov. NCT04820530. Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy (APPOINT-PNH). Available from: https://clinicaltrials.gov/study/NCT04820530 Accessed May, 2025.
21. Kavanagh D, Bomback A, Vivarelli M, et al. Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy: Results from the Phase 3 APPEAR-C3G Trial. Presented at European Renal Association (ERA) Congress; May 25, 2024; Stockholm, Sweden.
22. Smith RJ, Kavanagh D, Vivarelli M, et al. Efficacy and safety of iptacopan in patients with C3 glomerulopathy: 12-Month results from the Phase 3 APPEAR-C3G study. Presented at American Society of Nephrology (ASN) Kidney Week 2024; October 23-27, 2024; San Diego, CA.
23. Novartis. Press release. Novartis receives FDA approval for Fabhalta® (iptacopan), offering superior hemoglobin improvement in the absence of transfusions as the first oral monotherapy for adults with PNH. Available from: https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-fabhalta-iptacopan-offering-superior-hemoglobin-improvement-absence-transfusions-first-oral-monotherapy-adults-pnh Accessed May, 2025.
24. Novartis. Press release. Novartis receives FDA accelerated approval for Fabhalta® (iptacopan), the first and only complement inhibitor for the reduction of proteinuria in primary IgA nephropathy (IgAN). Available from: https://www.novartis.com/news/media-releases/novartis-receives-fda-accelerated-approval-fabhalta-iptacopan-first-and-only-complement-inhibitor-reduction-proteinuria-primary-iga-nephropathy-igan Accessed May, 2025.
25. Novartis. Press release. Novartis receives third FDA approval for oral Fabhalta® (iptacopan) – the first and only treatment approved in C3 glomerulopathy (C3G). Available from: https://www.novartis.com/news/media-releases/novartis-receives-third-fda-approval-oral-fabhalta-iptacopan-first-and-only-treatment-approved-c3-glomerulopathy-c3g Accessed May, 2025.
26. Novartis. Press release. Novartis oral Fabhalta® (iptacopan) receives positive CHMP opinion for the treatment of adults living with C3 glomerulopathy (C3G). Available from: https://www.novartis.com/news/media-releases/novartis-oral-fabhalta-iptacopan-receives-positive-chmp-opinion-treatment-adults-living-c3-glomerulopathy-c3g Accessed May, 2025.
27. Fabhalta®. US FDA Prescribing information. East Hanover, NJ:Novartis Pharmaceuticals Corp; 2024. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218276s001lbl.pdf Accessed May, 2025.
28. Fabhalta®. EMA Summary of Product Characteristics. Novartis Europharm Limited; 2024. Available from: https://www.ema.europa.eu/en/documents/product-information/fabhalta-epar-product-information_en.pdf Accessed May, 2025.
29. Martín B, Smith RJH. C3 Glomerulopathy. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2025. Updated April 5, 2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1425/ Accessed May, 2025. 
30. Schena FP, Esposito P, Rossini M. A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease. Int J Mol Sci. 2020;21(2):525. 
31. Caravaca-Fontán F, Lucientes L, Cavero T, Praga M. Update on C3 Glomerulopathy: A Complement-Mediated Disease. Nephron. 2020;144(6):272-280. 
32. Clinicaltrials.gov. NCT04578834. Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients (APPLAUSE-IgAN). Available from: https://clinicaltrials.gov/study/NCT04578834 Accessed May, 2025.
33. Clinicaltrials.gov. NCT04889430. Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy (APPELHUS). Available from: https://clinicaltrials.gov/study/NCT04889430 Accessed May, 2025.
34. Clinicaltrials.gov. NCT05755386. Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN (APPARENT). Available from: https://clinicaltrials.gov/study/NCT05755386 Accessed May, 2025.
35. Clinicaltrials.gov. NCT05268289. Study of Efficacy and Safety of LNP023 in Participants With Active Lupus Nephritis Class III-IV, +/​- V. Available from: https://clinicaltrials.gov/study/NCT05268289 Accessed May, 2025.
    

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