Novartis announces iptacopan met Phase II study primary endpoint in rare kidney disease IgA nephropathy (IgAN)
- Phase II primary endpoint results forinvestigational iptacopan in IgANdemonstrated effectiveand clinically meaningful reduction of proteinuria1 – a key risk predictor in kidney disease progression2
- Iptacopan also showed a trend toward stabilization of kidney function1; Phase III clinical trial APPLAUSE is underway
- There are no currently approved treatments for IgAN – a rare and oftenprogressive kidney disease that mainly affectsyoung adults and can progress to kidney failure3-7
- Iptacopan is in development for several complement-driven renal diseases (CDRDs), including IgAN and C3 glomerulopathy (C3G), and the blood disorder paroxysmal nocturnal hemoglobinuria (PNH), targeting a key driver of these diseases
Basel, June 06, 2021 — Novartis today announced Phase II primary endpoint data showing investigational iptacopan (LNP023) – a first-in-class, oral, targeted factor B inhibitor – reduced protein in the urine (proteinuria), an increasingly recognized surrogate marker correlating with progression to kidney failure2, and showed promise in stabilizing kidney function in patients with IgA nephropathy (IgAN)1. The data were presented at the 58th ERA-EDTA Congress held virtually from June 5–8, 2021.
In the Phase II study (NCT03373461), patients (n=112) with IgAN were randomized to placebo or different doses of iptacopan1. The primary endpoint was met with a statistically significant (p=0.038) dose response effect on reduction in proteinuria (as measured by 24-hour urinary protein to creatine ratio [UPCR 24h]) with iptacopan vs. placebo, at 90 days1. At the highest dose of 200mg twice daily a 23% reduction in proteinuria was predicted, compared with placebo, at 90 days1.
“IgAN is a devastating disease with no currently approved treatments. These efficacy data, seen after 90 days of treatment, along with the safety profile, offer hope that inhibition of the alternative complement pathway with iptacopan may be an effective way to delay IgAN disease progression,” said study lead author Jonathan Barratt, Professor of Renal Medicine, University of Leicester and nephrology consultant, Leicester General Hospital. “These data highlight the ability of iptacopan to address one of the key drivers for this disease and its potential to provide a much-needed, targeted treatment for people living with IgAN.”
Iptacopan also demonstrated a trend towards stabilizing kidney function, as assessed by estimated glomerular filtration rate (eGFR)1: a key measure of kidney clearance function that estimates the rate of blood passing through and being filtered by the kidneys8. Additionally, iptacopan showed a favorable safety and tolerability profile1.
“Complement-driven renal diseases, such as IgAN, are devastating and mostly affect young adults, imposing a high disease burden. These new data in IgAN add to the growing body of evidence around the potential of iptacopan to target a key driver in these rare renal diseases,” said John Tsai, Head of Global Drug Development and Chief Medical Officer at Novartis. “Conscious of the significant patient need for disease-modifying treatment options, we are rapidly advancing clinical development of iptacopan with the Phase III IgAN trial APPLAUSE already underway.”
Iptacopan is the most advanced asset in the company’s nephrology pipeline and targets the alternative complement pathway, a key driver of complement-driven renal diseases (CDRDs). New data from an interim analysis of a Phase II study of iptacopan in C3 glomerulopathy (C3G) – another CDRD – will also be presented at the congress on Monday 07 June 2021 at 12:30 p.m. CEST9. Novartis has plans to initiate additional Phase III studies in other renal indications.
Iptacopan is also in development for a life-threatening blood disorder, paroxysmal nocturnal hemoglobinuria (PNH). Based on disease prevalence and positive data from Phase II studies, iptacopan has received EMA orphan drug designation in IgAN10, orphan drug designations from the FDA and EMA in C3G and PNH11, FDA Breakthrough Therapy Designation in PNH12, and EMA PRIME designation for C3G13.
About the studies
NCT03373461 is a Phase II randomized, double-blind, placebo-controlled, dose-ranging, parallel-group adaptive design study to investigate the efficacy and safety of iptacopan in primary IgAN1. It is the first study to report the efficacy and safety of selective inhibition of the alternative complement pathway in IgAN1. The primary endpoint, and the primary aim of the interim analysis presented at the 2021 ERA-EDTA Congress, was to evaluate the dose response effect of iptacopan versus placebo on the reduction in urinary protein to creatinine ratio (UPCR 24h) at 90 days of treatment1. Secondary endpoints include safety and tolerability of iptacopan, eGFR, and biomarkers reflecting activity of the alternative complement pathway1.
Iptacopan is an investigational, first-in-class, orally administered factor B inhibitor of the alternative complement pathway, targeting one of the key drivers of these diseases14-16. It has the potential to become the first targeted therapy to delay progression to dialysis in IgAN. Discovered at the Novartis Institutes for BioMedical Research, iptacopan is currently in development for a number of CDRDs where significant unmet needs exist, including IgAN, C3G, atypical hemolytic uremic syndrome (aHUS), and membranous nephropathy (MN), as well as the blood disorder PNH.
While Novartis has a 35-year history in kidney transplantation treatments, iptacopan is the first treatment in the nephrology pipeline addressing CDRDs. Our aim is to transform treatment by targeting one of the key drivers of these rare and often progressive diseases15 and, in doing so, potentially extend dialysis-free life for people with CDRDs.
About complement-driven renal diseases (CDRDs)
CDRDs, which include IgAN, are thought to be partly caused by an overactivation of the alternative complement pathway – part of the immune system – creating an inflammatory response, which can lead to kidney damage15,17-20. CDRDs mainly affect young adults, and can often lead to kidney failure which requires dialysis or transplantation and can lead to premature death3-7.
IgAN patients with persistent proteinuria levels of ≥1 g/day are at higher risk of disease progression, with about 30% progressing to kidney failure within 10 years21-23. Corticosteroids are often used to treat IgAN, as there are no approved treatment options. However, data on their efficacy have been inconsistent and this class of drugs has well-known side effects, which can be severe24-26.
There is a need for effective and well-tolerated, targeted therapies for IgAN that can delay disease progression.
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.
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 email@example.com
- Barratt J, Rovin B, Zhang H, et al. Interim analysis of a Phase 2 dose ranging study to investigate the efficacy and safety of iptacopan in primary IgA nephropathy. Presented at the ERA-EDTA congress.
- Thompson A, Carroll K, Inker LA, et al. Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy. Clin J Am Soc Nephrol. 2019;14(3):469–481.
- McGrogan A, Franssen CFM, de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transplant. 2011;26(2):414–430.
- Nam KH, Kie JH, Lee MJ, et al. Optimal proteinuria target for renoprotection in patients with IgA nephropathy. PLoS One. 2014;9(7):e101935.
- Abbasi MA, Chertow GM, Hall YN. End-stage renal disease. BMJ Clin Evid. 2010;2010.
- Bulut IK, Mir S, Sozeri B, et al. Outcome results in children with IgA nephropathy: a single center experience. Int J Nephrol Renovasc Dis. 2012;5:23–28.
- Selvaskandan H, Cheung CK, Muto M, et al. New strategies and perspectives on managing IgA nephropathy. Clin Exp Nephrol. 2019;23(5):577–588.
- Lopez-Giacoman S, Madero M. Biomarkers in chronic kidney disease, from kidney function to kidney damage. World J Nephrol. 2015;4(1):57–73.
- Wong E, Praga M, Nester C, et al. Iptacopan (LNP023): a novel oral complement alternative pathway factor B inhibitor safely and effectively stabilises eGFR in C3 glomerulopathy. To be presented at the ERA-EDTA congress.
- 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 April 2021.
- Novartis. Data on file.
- 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 April 2021.
- 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 April 2021.
- Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I – molecular mechanisms of activation and regulation. Front Immunol. 2015;6:262.
- Schubart A, Anderson K, Mainolfi N, 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.
- Sarma JV, Ward PA. The complement system. Cell Tissue Res. 2011;343(1):227–235.
- Willows J, Brown M, Sheerin NS. The role of complement in kidney disease. Clin Med. 2020;20(2):156–160.
- Łukawska E, Polcyn-Adamczak M, Niemir ZI. The role of the alternative pathway of complement activation in glomerular diseases. Clin Exp Med. 2018;18(3):297–318.
- Koscielska-Kasprzak K, Bartoszek D, Myszka M, Zabinska M, Klinger M. The complement cascade and renal disease. Arch Immunol Ther Exp (Warsz). 2014;62(1):47–57.
- De Vriese AS, Sethi S, Van Praet J, Nath KA, Fervenza FC. Kidney disease caused by dysregulation of the complement alternative pathway: An etiologic approach. J Am Soc Nephrol. 2015;26(12):2917–2929.
- Reich HN, Troyanov S, Scholey JW, Cattran DC, Toronto Glomerulonephritis Registry. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol. 2007;18(12):3177–3183.
- Sevillano AM, Gutiérrez E, Yuste C, et al. Remission of hematuria improves renal survival in IgA nephropathy. J Am Soc Nephrol. 2017;28(10):3089–3099.
- Xie J, Kiryluk K, Wang W, et al. Predicting Progression of IgA Nephropathy: New Clinical Progression Risk Score. PLoS One. 2012;7(6):e38904.
- Ramamoorthy S, Cidlowski JA. Corticosteroids-Mechanisms of Action in Health and Disease. Rheum Dis Clin North Am. 2016;42:15–31.
- Coppo R. Corticosteroids in IgA Nephropathy: Lessons from Recent Studies. J Am Soc Nephrol. 2017;28:25–33.
- Rodrigues JC, Haas M, Reich HN. IgA Nephropathy. Clin J Am Soc Nephrol. 2017;12(4):677–686.
# # #
Novartis Media Relations
|Jamie Bennett||Phil McNamara|
|Novartis US External Communications||Novartis Cardio-Renal- Metabolic|
|+1 862 778 3503||Communications|
|firstname.lastname@example.org||+1 862 778 0218 (direct)|
|+1 862 274 5255 (mobile)|
|Novartis US External Communications|
|+1 862 579 8456 (mobile)|
Novartis Investor Relations
Central investor relations line: +41 61 324 7944
|Samir Shah||+41 61 324 7944||Sloan Simpson||+1 862 778 5052|
|Thomas Hungerbuehler||+41 61 324 8425|
|Isabella Zinck||+41 61 324 7188|
To view this piece of content from ml-eu.globenewswire.com, please give your consent at the top of this page.
One Liberty Plaza - 165 Broadway
NY 10006 New York
GlobeNewswire 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
Subscribe to all the latest releases from GlobeNewswire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from GlobeNewswire
New Zolgensma data demonstrate age-appropriate development when used presymptomatically and rapid, clinically meaningful efficacy in symptomatic children, even those with severe SMA at baseline18.6.2021 18:30:00 CEST | Press release
All children (100%) treated presymptomatically in the SPR1NT two-copy cohort survived without respiratory or nutritional support, and sat independently for ≥30 seconds, most (11/14) within the WHO window of expected normal development The majority of children (82%) treated in STR1VE-EU achieved developmental motor milestones not observed in the natural history of SMA Type 1, including patients with more severe disease More than 1,200 patients have now been treated with Zolgensma globally across clinical trials, managed access programs, and in the commercial setting1 Basel, June 18, 2021– Novartis today announced data that reinforce the transformational benefit of Zolgensma® (onasemnogene abeparvovec), an essential, one-time treatment and the only gene therapy for spinal muscular atrophy (SMA). New late-breaker data from the completed two-copy cohort of the Phase 3 SPR1NT clinical trial demonstrate age-appropriate milestone development in presymptomatic children with SMA without respira
The results of the private placement of Subordinated Convertible Notes and private placement of Secured Notes of AS PRFoods / transactions with persons connected with the issuer18.6.2021 16:22:48 CEST | Press release
THIS NOTICE IS NOT INTENDED FOR PUBLICATION, ALLOCATION OR TRANSMISSION, IN PART OR WHOLLY, DIRECTLY OR INDIRECTLY, IN THE UNITED STATES, AUSTRALIA, CANADA, HONG KONG, JAPAN, NEW ZEALAND, SINGAPORE, SOUTH AFRICA, OR ELSEWHERE THE DISCLOSURE OR TRANSMISSION OF THIS INFORMATION IS NOT ALLOWED. By a company announcement dated 04.06.2021, AS PRFoods (hereinafter "PRFoods") informed investors that it was conducting an issue of subordinated convertible notes, whereunder PRFoods is to issue up to 350 subordinated convertible notes, with the maximum aggregate nominal value of up to EUR 3,500,000, nominal value of EUR 10,000 per subordinated convertible note, interest rate of 7% per annum and maturity date on 01.10.2025 (hereinafter the “ConvertibleNotes”). The subscription period for the Convertible Notes ended on 14.06.2021. In course of the private placement, investors subscribed for 237 Convertible Notes, with the aggregate nominal value of EUR 2,370,000, i.e. for approximately 67% of the m
CONDITIONS FOR PURCHASES OF CORPORATE BONDS18.6.2021 16:20:00 CEST | Press release
Bid procedure, 2021-06-23BondsBonds issued in SEK by Swedish non-financial undertakings. The following bonds are eligible for delivery: RIKSHEM AB: SE0011452507, 2023-07-18 RIKSHEM AB: SE0011869981, 2023-05-08 EPIROC AB: XS1918042364, 2023-12-06 EPIROC AB: XS2258568778, 2026-05-18 SCANIA CV AB: XS2042641121, 2022-08-22 SCANIA CV AB: XS2332891089, 2023-04-19 AB INDUSTRIVARDEN: SE0011869668, 2022-02-28 AB INDUSTRIVARDEN: SE0012676724, 2023-02-20 SVENSK FASTIGHETS FIN: SE0012194058, 2022-02-28 SVENSK FASTIGHETS FIN: SE0012676872, 2022-09-07 Delivery of a Bond may not occur if the Counterparty has purchased the Bond from the issuer more recently than one month prior to the date of announcement of the Special terms, that is, the purchase may not have taken place after: 2021-05-23Bid date2021-06-23Bid times10.00-11.00 (CET/CEST) on the Bid dateRequested volume (corresponding nominal amount)SE0011452507: 30 mln SEK +/-30 mln SEK SE0011869981: 30 mln SEK +/-30 mln SEK XS1918042364: 30 mln SEK
CONDITIONS FOR RIKSBANK BID PROCEDURE KOMMUNINVEST BONDS18.6.2021 16:20:00 CEST | Press release
Bid procedure, 2021-06-22BondsKOMMUNINVEST I SVERIGE: 2311. SE0010948240. 2023-11-13 KOMMUNINVEST I SVERIGE: 2505, SE0011414010, 2025-05-12 KOMMUNINVEST I SVERIGE: 2805, SE0015660139, 2028-05-12 BidsBids on interest and volume are entered via Bloomberg Bond Auction SystemBid date2021-06-22Bid times10.00-11.00 (CET/CEST) on the Bid dateRequested volume (corresponding nominal amount)2311: 500 mln SEK +/-250 mln SEK 2505: 1000 mln SEK +/-500 mln SEK 2805: 750 mln SEK +/-350 mln SEK Highest permitted bid volume (corresponding nominal amount)2311: 500 mln SEK per bid 2505: 1000 mln SEK per bid 2805: 750 mln SEK per bid Lowest permitted bid volume (corresponding nominal amount)SEK 50 million per bidExpected allocation timeNot later than 11.15 (CET/CEST) on the Bid dateDelivery and payment date2021-06-24Delivery of bondsTo the Riksbank's account in Euroclear Sweden AB's securities settlement system 1 4948 6383General Terms and ConditionsGeneral Terms and Conditions General Terms and Condition
CONDITIONS FOR THE RIKSBANK´S PURCHASES OF COMMERCIAL PAPER18.6.2021 16:20:00 CEST | Press release
Bid procedure, 2021-06-23CertificateCommercial paper issued in SEK by non-financial companies with their registered office in Sweden and with a remaining maturity of up to six months on the Bid date. i.e. with the latest maturity date as of 2021-12-23 Delivery may not be made in commercial paper purchased by the Counterparty from the issuer less than one week prior to the date for announcing the Special terms, i.e. the purchase may not have been made after 2021-06-11 BidsCounterparties may make one bid per Credit rating class and maturity class. Bids are made to tel 08-696 69 70 and confirmed by e-mail to EOL@riksbank.se.Bid date2021-06-23Bid times09.00-09.30 (CET/CEST) on the Bid dateRequested volume (corresponding nominal amount)SEK 4 billionHighest permitted bid volume (corresponding nominal amount)The total bid volume from one Counterparty for the two Credit rating classes may not exceed SEK 4 billion. No bid may contain Commercial paper in excess of SEK 250 million issued by the s
Eolus förvärvar två fullt tillståndsgivna svenska vindkraftsprojekt18.6.2021 16:15:00 CEST | Pressemelding
Hässleholm den 18 juni 2021 Eolus har tecknat avtal med RWE om att förvärva två fullt tillståndsgivna svenska vindkraftsprojekt. Projekten som omfattar 99 MW är lokaliserade i SE3 och Eolus kommer under sommaren att påbörja försäljningsprocessen med ambitionen att teckna avtal med en investerare under hösten 2021. Projekten är belägna i Avesta kommun (Skallberget/Utterberget) och Hedemora kommun (Tjärnäs) och omfattar totalt vardera 74,4 MW och 24,8 MW. Projekten är fullt tillståndsgivna. Eolus kommer under sommaren att påbörja försäljningsprocessen med ambitionen att teckna ett avtal med en investerare under hösten 2021. Planerad driftsättning är under 2023. För ytterligare information kontakta: Per Witalisson, VD, telefon +46 (0)70-265 16 15 Johan Hammarqvist, kommunikationschef, telefon +46 (0)720-50 59 11 Kort om Eolus Eolus Vind är en av Nordens ledande projektörer av vindkraftsanläggningar. Eolus skapar värden i alla led inom ramen för projektutveckling och drift av vindkraftsanl
Eolus acquires two fully permitted wind power projects in Sweden18.6.2021 16:15:00 CEST | Press release
Hässleholm, Sweden, June 18, 2021 Eolus has signed an agreement to acquire two fully permitted wind power projects in Sweden from RWE. The projects located in SE3 totals about 99 MW and Eolus will during summer initiate the sales process with the ambition to sign an agreement with an investor during the autumn of 2021. The projects are located in Avesta municipality (Skallberget/Utterberget) and Hedemora municipality (Tjärnäs) and totals respectively 74.4 MW and 24.8 MW. The projects are fully permitted. Eolus will during the summer initiate the sales process with the ambition to sign an agreement with an investor during the autumn of 2021. Planned commissioning is during 2023. For further information contact: Per Witalisson, CEO, +46 70-265 16 15 Johan Hammarqvist, Head of Communications, +46 720 50 59 11 About Eolus: Eolus Vind AB is one of the leading wind power developers in the Nordics. Eolus is active in the whole value chain from development of green field projects to constructi