Dec12023

Ad hoc announcement pursuant to Art.53LR

  • Phase III APPEAR-C3Gstudy met its primary endpoint，demonstrating superiority of iptacopan vs.placebo in proteinuria reduction at six-month analysis1个打开；iptacopan was consistent with previously reported data1-3
  • C3glomerulopathy（C3G）isan ultra-rare complement-mediated kidney disease，对钢筋混凝土进行预处理后，应将其安装在钢筋混凝土上4-7打开；currently no treatments address the underlying cause of C3G7-9
  • Novartis plans to review results with global health authorities to enable potential submissions in 2024；data will be submitted for presentation at an upcoming medical meeting
  • Iptacopan demonstrated positive Phase III results in IgA nephropathy（IgAN）at the interim analysis and a late-stage development program is ongoing across four investigational indications10-14

Basel，December112023—Novartis today announced positive topline results from the six-month，double-blind period of the Phase III APPEAR-C3G study of iptacopan for the treatment of patients with C3glomerulopathy（C3G）1个.The study met its primary endpoint，with iptacopan（200mg twice daily）demonstrating superiority compared to placebo in providing clinically meaningful and statistically significant proteinuria（protein urine）reduction on top of background therapy at six months1个.The safety profile of iptacopan was consistent with previously reported data1-3。

The data will be submitted for presentation at an upcoming medical meeting and discussed with global health authorities anticipating potential regulatory submissions in 2024.The APPEAR-C3Gstudy continues for asix-month，open-label period，inwhich all patients receiptapcopan，incloudition acebo12，15.In addition，钢轨安装安装安装安装安装板12，15。

“People living with C3glomerulopathy have no approved treatment options indicated forthis progressive disease，posing many challenges and uncertainty for these mostly young patients，”said Sreeram Aradhye，M.D.，President，Development and Chief Medical Officer，Novartis。“These positive results demonstrate the potential of iptacopan to provide clinically meaningful benefit in C3G and add to our growing body of evidence that supports its use across multiple complement-mediated diseases.”

Iptacopan，which is also being investigate in other complement-mediated diseases，recently achieved positive interim results in IgA nephropathy（IgAN）10.On December52023，FDA approved iptacopan，under the brand name Fabhalta®，as the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria（PNH），然后，在该区域，在该区域，在该区域，在该区域16-17。

About the study
APPEAR-C3G（NCT04817618）is a Phase III multicenter，randomized，double-blind，parallel group，placebo-controlled study to evaluate the efficacy and safety of twice-daily oral iptacopan（200mg）in C3G patients12，15.In addition to the announced topline results for adult patients with C3G，钢轨安装安装安装安装安装板12，15.The study comprises asix-month double-blind period where patients were randomized1:1 to receive iptacopan or placebo on top of background therapy，followed by asix-month open-label period where all patients receive iptacopan12，15。

用于修复six-month double-blind period was proteinuria reduction at six months as measured by urine protein to creatinine ratio（UPCR）12，15.The primary endpoint for the open-label period is proteinuria reduction at12months（both treatms）and a comparison between proteinuria reduction at6and12months（placebo arm）12，15.Secondary endpoints include change in estimated glomerular filtration rate（eGFR），proportion of participants meeting composite renal endpoint criteria（≤15%reduction in eGFR and≥50%reduction in UPCR），change in glomerular inflammation（asmeasured by disease total activity score in a renal biopsy），按asmeasured by FACIT-Fatigue score，和安全性12，15。

About C3G
C3glomerulopathy（C3G）is an ultra-rare，progressive complement-mediated kidney disease that initially presents in mostly children and young adults4-6，18.Each year，approximately1-2people per million worldwide are newly diagnosed with C3G，aform of membrano proliferative glomerulonephritis（MPGN）4个。

C3G，overactivation of the alternative complement pathway–part of the immune system–causes deposits of C3 protein to build up in kidney glomeruli（anetwork of blood vessels that filter waste and remove extra fluids from the blood）4,7，18-20.This triggers inflammation and glomerular damage that results in proteinuria（protein urine），hematuria（blood in urine）and reduced kidney function4,7，18-20.Approximately50%of C3Gpatients progress to kidney failure within10years of diagnosis，预应力运输装置6-7，with over55%of patients with C3G experiencing disease recurrence post-transplant21-24。

About iptacopan
Iptacopan is an oral，Factor B inhibitor of the alternative complement pathway第十七节：。

Discovered at Novartis，iptacopan recently demonstrated clinically meaningful and highly statistically significant proteinuria reduction in patients with IgAN nephropathy（IgAN）at the interim analysis in the Phase III APPLAUSE-IgAN study（NCT04578834）10.Iptacopan is also being investigated in Phase III studies for atypical hemolytic uremic syndrome（aHUS）（APPELHUS[NCT04889430]）and immune complex membrano proliferative glomerulonephritis（IC-MPGN）（APPARENT[NCT05755386]）13-14.On December52023，FDA approved iptacopan，under the brand name Fabhalta®，as the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria（PNH），然后，在该区域，在该区域，在该区域，在该区域16-17。

Based on disease prevalence，unmet needs and data from Phase II studies，iptacopan has received FDA Breakthrough Therapy Designation in C3G and PNH，orphan drug designations from the FDA and EMA in PNH and C3G，EMA PRIME designation for C3G，and EMA orphan drug designation in IgAN25-28. 

Novartis and renal
Chronic kidney disease（CKD）affects 1 in 10 people worldwide29.People living with CKD may ultimately progress to kidney failure，修理主管道设计30-31.  

At Novartis，our mission in nephrology began40years ago with transplantation and immunosuppression.Our commitment continues today through our aim to transform the lives of people living with kidney diseases byinvestigating new options that may slow kidney disease progression and extend dialysis-free life

We are committed to advancing the development of our renal portfolio，exploring potential therapeutic options to address the current unmet need for people living with C3G，IgAN，IC-MPGN，lupus nephritis and aHUS

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，”“plans，”“may，”“could，”“investigation，”“progressing”“development，”“upcoming，”“ongoing，”“aim，”or similar terms，orby express or implied discussions regarding potential marketing approvals，new indications or labeling for iptacopan，orregarding potential future revenues from iptacopan.You should not place undue reliance on these statements.Such forward-looking statements are baseed on our current belies and expectures， 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 iptacopan 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 iptacopan will be commercially successful in the future.In particular，our expectations regarding iptacopan could be affected by，among other things，the uncertainherent 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， 城市公共公共交通和reimbursement pressures and requirement为increased pricing transparency， including the effect 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 Form20-F on file with the US Securities and Exchange Commission.Novartis is 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 reas ase as rease as suformation ofn，future events or otherwise。

About Novartis
Novartis is an innovative medicines company.Every day，we work to reimagine medicine to improve and extend people’s live s so that patients，healthcare professionals and societies are empowed in the face of serious disease.Our medicines reach more than250million people worldwide。

Reimagine medicine with us:Visit us athttps://www.novartis.comand connect with us onLinkedIn单击功能区上，Facebook单击功能区上，X/Twitterand，andInstagram。

参考，参考

  1. Novartis data on file。
  2. Novartis iptacopan meets primary endpoints in Phase II study in rare kidney disease C3glomerulopathy（C3G）。Novartis.Acceed December62023。https://www.novartis.com/news/media-releases/novartis-iptacopan-meets-primary-endpoints-phase-ii-study-rare-kidney-disease-c3-glomerulopathy-c3g
  3. Wong E，Nester C，Cavero T，et al.Efficacy and Safety of Iptacopan in Patients With C3Glomerulopathy。Kidney Int Rep.2023；8:2754-2764。
  4. Schena FP，Esposito P，Rossini M.A Narrative Review on C3Glomerulopathy:A Rare Renal Disease。Int J Mol Sci。2020；21（2）：525。
  5. Smith RJ，Alexander J，Barlow PN，et al.New Approaches to the Treatment of Dense Deposit Disease。J Am Soc Nephrol。2007；18（9）：2447-2456。
  6. Martin B，Smith RJH.In:Adam MP，Ardinger HH，Pagon RA，et al.C3Glomerulopathy.GeneReviews®[Internet]。Updated2018.University of Washington，Seattle；1993-2022。
  7. Smith RJH，Appel GB，Blom AM，et al.C3Glomerulopathy–Understanding a Rare Complement-driven Renal Disease。Nat Rev Nephrol.2019；15（3）：129-143。
  8. Goodship TH，Cook HT，Fakhouri F，et al.Atypical Hemolytic Uremic Syndrome and C3Glomerulopathy:Conclusions froma“Kidney Disease:Improving Global Outcomes”（KDIGO）Controversies Conference。Kidney Int.2017；91（3）：539-551。
  9. Kidney Disease:Improving Global Outcomes（KDIGO）Glomerular Diseases Work Group。KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases。Kidney Int.2021；100（4S）：S1-S276。
  10. Novartis investigational iptacopan Phase III study demonstrates clinically meaningful and high ly statistically significant proteinuria reduction in patients with IgA nephropathy（IgAN）。Novartis.Acceed December62023。https://www.novartis.com/news/media-releases/novartis-investigational-iitii-study-demonstrates-clinically-meaningful-and-highly-statistically-significant-proteinuria-reduction-patients-iga-nephropathy-igan
  11. Novartis Pharmaceuticals.Study of Efficacy and Safety of LNP023in Primary IgA Nephropathy Patients（APPLAUSE-IgAN）。clinicaltrials.gov.Acceed December62023。https://clinicaltrials.gov/study/NCT 04578834
  12. Novartis Pharmaceuticals.Study of Efficacy and Safety of Iptacopan in Patients With C3Glomerulopathy.（APPEAR-C3G）。clinicaltrials.gov.Acceed December62023。https://clinicaltrials.gov/study/NCT 04817618
  13. Novartis Pharmaceuticals.Efficacy and Safety of Iptacopan（LNP023）in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy（APPELHUS）。clinicaltrials.gov.Acceed December62023。https://clinicaltrials.gov/study/NCT 04889430
  14. Novartis Pharmaceuticals.Study of Effficacy and Safety of Iptacopan in Participats With IC-MPGN（APPARENT）。clinicaltrials.gov.Acceed December62023。https://clinicaltrials.gov/study/NCT 05755386
  15. Bomback AS，Kavanagh D，Vivarelli M，et al.Alternative Complement Pathway Inhibition With Iptacopan for the Treatment of C3Glomerulopathy-Study Design of the APPEAR-C3G Trial。Kidney Int Rep.2022；7（10）：2150-2159。
  16. 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.Novartis.Acceed December62023。https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-fabhalta-iptacopan-offering-superior-hemoglobin-improvement-absence-transfusions-first-oral-monotherapy-adults-pnh
  17. Iptacopan Prescribing Information.East Hanover，NJ:Novartis Pharmaceuticals Corp；December2023。
  18. edjeral-Thomas NR，O'Shaughnessy MM，O'Regan JA，et al.C3Glomerulopathy:Clinicopathologic Features and Predictors of Outcome。Clin J Am Soc Nephrol.2014；9（1）：46-53。
  19. Ravindran A，Fervenza FC，Smith RJH，Sethi S.C3Glomerulopathy Associated with Monoclonal Ig is a Distinct Subtype。Kidney Int.2018；94（1）：178-186。
  20. Caravaca-Fontán F，Lucientes L，Cavero T，Praga M.Update on C3Glomerulopathy:A Complement-Mediated Disease。Nephron.2020；144（6）：272-280。
  21. Servais A，No嶅l LH，Roumenina LT，et al.Acquired and Genetic Complement Abnormalities Play a Critical Role in Deposit Disease and Other C3Glomerulopathies。Kidney Int.2012；82（4）：454-464。
  22. Zand L，Lorenz EC，Cosio FG，et al.Clinical Findings，Pathology，and Outcomes of C3GN after Kidney Transplantation。J Am Soc Nephrol.2014；25（5）：1110-1117。
  23. Regunathan-Shenk R，Avasare RS，Ahn W，et al.Kidney Transplantation in C3Glomerulopathy:A Case Series。Am J Kidney Dis.2019；73（3）：316-323。
  24. Caravaca-Fontán F，Polanco N，Villacorta B，et al.Recurrence of Immune Complex and Complement-mediated Membranoproliferative Glomerulonephritis in Kidney Transplantation。Nephrol Dial Transplant.2023；38（1）：222-235。
  25. Novartis investigational oral therapy iptacopan（LNP023）receives FDA Breakthrough Therapy Designation for PNH and Rare Pediatric Disease Designation for C3G。Novartis.Acceed December62023。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
  26. Novartis announces European Medicines Agency（EMA）has granted orphan drug designation for iptacopan（LNP023）in IgA nephropathy（IgAN）。Novartis.Acceed December62023。https://www.novartis.com/news/media-releases/novartis-announces-european-medicines-agency-ema-has-granted-orphan-drug-designation-iptacopan-lnp023-iga-nephropathy-igan
  27. Novartis received European Medicines Agency（EMA）PRIME designation for iptacopan（LNP）inC3glomerulopathy（C3G）。Novartis.Acceed December62023。https://www.novartis.com/news/media-releases/novartis-received-european-medicines-agency-ema-prime-designation-iptacopan-lnp-c3-glomerulopathy-c3g
  28. Novartis data on file。
  29. National Kidney Foundation.Global Facts:About Kidney Disease.Acceed December62023https://www.kidney.org/kidneydisease/global-facts-about-kidney-disease
  30. NHS.Kidney Disease.Acceed December62023。https://www.nhs.uk/conditions/kidney-disease/
  31. National Kidney Foundation.Chronic kidney disease（CKD）。Accessed December62023https://www.kidney.org/atoz/content/about-chronic-kidney-disease

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