GlobeNewswire by notified

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

Share
  • 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.

Disclaimer
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 https://www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnews
For Novartis multimedia content, please visit https://www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com

References

  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: https://www.novartis.com/news/media-releases/novartis-investigational-oral-therapy-iptacopan-lnp023-receives-fda-breakthrough-therapy-designation-pnh-and-rare-pediatric-disease-designation-c3g. 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: https://www.novartis.com/news/media-releases/novartis-announces-iptacopan-met-phase-ii-study-primary-endpoint-rare-kidney-disease-iga-nephropathy-igan. 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: https://www.novartis.com/news/media-releases/novartis-announces-new-interim-analysis-phase-ii-data-iptacopan-rare-kidney-disease-c3-glomerulopathy-c3g. 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: https://www.novartis.com/news/media-releases/novartis-received-european-medicines-agency-ema-prime-designation-iptacopan-lnp-c3-glomerulopathy-c3g. 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: https://www.novartis.com/news/media-releases/novartis-announces-european-medicines-agency-ema-has-granted-orphan-drug-designation-iptacopan-lnp023-iga-nephropathy-igan. Accessed March 2021.

# # #

Novartis Media Relations
E-mail: media.relations@novartis.com

Anja von Treskow
Novartis Strategy & Financial
Communications
+41 79 392 8697 (mobile)
anja.von_treskow@novartis.com



Julie Masow
Novartis US External Communications
+1 862 579 8456 (mobile)
julie.masow@novartis.com
Michael Billings
Novartis Oncology Communications
+1 862 778 8656 (direct)
+1 201 400 1854 (mobile)
michael.billings@novartis.com



Phil McNamara
Novartis Cardio-Renal- Metabolic Communications
+1 862 778 0218 (direct)
+1 862 274 5255 (mobile)
philip.mcnamara@novartis.com

Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations@novartis.com

CentralNorth America
Samir Shah+41 61 324 7944Sloan Simpson+1 862 778 5052
Thomas Hungerbuehler+41 61 324 8425
Isabella Zinck+41 61 324 7188
To view this piece of content from www.globenewswire.com, please give your consent at the top of this page.
To view this piece of content from ml-eu.globenewswire.com, please give your consent at the top of this page.

About GlobeNewswire by notified

GlobeNewswire by notified
GlobeNewswire by notified
One Liberty Plaza - 165 Broadway
NY 10006 New York

https://notified.com

GlobeNewswire by notified is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.

Subscribe to releases from GlobeNewswire by notified

Subscribe to all the latest releases from GlobeNewswire by notified by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from GlobeNewswire by notified

Public announcement in accordance with article 7:97, §4/1 of the Belgian Companies and Associations Code (“BCAC”) concerning a capital increase by contribution in kind29.3.2024 07:00:00 CET | Press release

Press release Brussels, 29 March 2024 Regulated information – Inside information Public announcement in accordance with article 7:97, §4/1 of the Belgian Companies and Associations Code (“BCAC”) concerning a capital increase by contribution in kind On 20 November 2023, Orange Belgium SA (the “Company”) received notification from Nethys SA (“Nethys”) of its wish to contribute its 25% + 1 shareholding in VOO Holding SA (“VOO”) to the capital of the Company, provided that such contribution results in Nethys holding at least 11% of the Company's share capital (after contribution), pursuant to the provisions of the shareholders' agreement entered into by and between the Company, Atlas Services Belgium SA (“ASB”) and Nethys on 2 June 2023. Nethys can be considered a “related” party to the Company within the meaning of the IAS standards, as it has significant influence over VOO within the meaning of IAS and VOO is part of the group to which the Company belongs. Date and value of the planned t

McWhorter Foundation Combats Nelson Peltz’s Outdated Ideologies and Advocates for Sustainable Inclusivity In Corporate Leadership29.3.2024 06:59:56 CET | Press release

PALM BEACH, Calif., March 29, 2024 (GLOBE NEWSWIRE) -- C.K. McWhorter, chairman of the McWhorter Foundation, voices concerns over outdated perspectives in corporate leadership, exemplified by recent remarks from Nelson Peltz regarding Disney's film direction. After encountering instances of racism and exclusivity on Town of Palm Beach Island (known as home to Jeffrey Epstein, Nelson Peltz and others), McWhorter reflects on the disconnect between elite boardroom discussions and the realities faced by diverse communities. While briefly meeting Nelson Peltz and shaking hands after both departed separate lunches, McWhorter initially respected his insights. However, recent comments made by Peltz suggesting Disney should avoid inclusive films have raised eyebrows and prompted McWhorter to speak out. "It's concerning when influential figures like Peltz advocate against inclusivity in entertainment," McWhorter comments. "The future is in diversity and representation, especially as millennial a

Junshi Biosciences Announces 2023 Full Year Financial Results and Provides Corporate Updates29.3.2024 05:24:27 CET | Press release

SHANGHAI, China, March 29, 2024 (GLOBE NEWSWIRE) -- Shanghai Junshi Biosciences Co., Ltd (“Junshi Biosciences,” HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, announced its financial results for the full year of 2023 and provided corporate updates. FINANCIAL HIGHLIGHTS Total revenue was approximately RMB1,503 million during 2023. The revenue from pharmaceutical products increased by approximately 58% compared to 2022. The sales revenue of TUOYI® (toripalimab) was approximately RMB919 million, representing an increase of approximately 25% compared to the previous year.Total research and development (“R&D”) expenses were approximately RMB1,937 million in 2023, representing a decrease of approximately 19% compared to 2022. The decrease in R&D expenses was mainly due to the strategic management of R&D investments in certain early-stage pipelines, while optimizing resource all

Robex Announces Share Consolidation29.3.2024 00:30:00 CET | Press release

NOT FOR DISTRIBUTION TO U.S. NEWSWIRE SERVICES OR DISSEMINATION IN THE UNITED STATES QUEBEC CITY, March 28, 2024 (GLOBE NEWSWIRE) -- Robex Resources Inc. ("Robex" or the "Company") (TSXV: RBX) announces today that its Board of Directors has approved the implementation of the consolidation of the issued and outstanding common shares of the Company approved by its shareholders on June 29, 2023, on the basis of one (1) post-consolidation common share for ten (10) pre-consolidation common shares (the "Consolidation"), which will take effect on April 1st, 2024 (the "Effective Date"). As a result, the Company's consolidated shares are expected to commence trading on the TSX Venture Exchange a few days after the Effective Date. After the Consolidation, the shares will have a new CUSIP number and a new ISIN number. The Consolidation will reduce the number of issued and outstanding common shares of the Company from approximately 844,054,403 common shares to 84,405,449 common shares upon complet

Golar LNG Limited - Announcement of filing of Form 20-F Annual Report28.3.2024 22:47:27 CET | Press release

Golar LNG Limited announces that it has filed its Form 20-F for the year ended December 31, 2023 with the Securities and Exchange Commission in the U.S. Form 20-F can be downloaded from the link below, is available on our website (www.golarlng.com) and shareholders may receive a hard copy free of charge upon request. March 28, 2024 The Board of Directors Hamilton, Bermuda Enquiries: Golar Management Limited: + 44 207 063 7900 Stuart Buchanan This information is subject to the disclosure requirements pursuant to Section 5-12 the Norwegian Securities Trading Act Attachment GLNG 2023 Annual Report Form 20-F

HiddenA line styled icon from Orion Icon Library.Eye