UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13a-16 or 15d-16 OF
THE SECURITIES EXCHANGE ACT OF 1934
Report on Form 6-K dated December 11, 2023
(Commission File No. 1-15024)
____________________
Novartis AG
(Name of Registrant)
Lichtstrasse 35
4056 Basel
Switzerland
(Address of Principal Executive Offices)
____________________
Indicate by check mark whether the registrant files or will file annual reports under cover
of Form 20-F or Form 40-F:
Form 20-F: ☒ |
|
Form 40-F: ☐ |
|
Novartis International AG Novartis Global
Communications CH-4002 Basel Switzerland
https://www.novartis.com
https://twitter.com/novartisnews |
MEDIA & INVESTOR
RELEASE
Novartis investigational iptacopan Phase III study
demonstrates clinically meaningful and statistically significant proteinuria reduction in patients with C3 glomerulopathy (C3G)
Ad hoc announcement pursuant to Art. 53 LR
| · | Phase III APPEAR-C3G study met its primary endpoint, demonstrating superiority of iptacopan vs.
placebo in proteinuria reduction at six-month analysis1; the safety profile of iptacopan was consistent with previously reported
data1-3 |
| · | C3 glomerulopathy (C3G) is an ultra-rare complement-mediated kidney disease, with approximately
50% of patients progressing to kidney failure within 10 years of diagnosis4-7; 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, December 11, 2023 — 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 C3 glomerulopathy (C3G)1.
The study met its primary endpoint, with iptacopan (200 mg twice daily) demonstrating superiority compared to placebo in providing clinically
meaningful and statistically significant proteinuria (protein in urine) reduction on top of background therapy at six months1.
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-C3G study continues for a six-month, open-label period,
in which all patients receive iptacopan, including those previously receiving placebo12,15. In addition, enrollment is ongoing
in a separate cohort of adolescent patients with C3G12,15.
“People living with C3 glomerulopathy have no approved treatment options indicated for this
progressive disease, posing many challenges and uncertainty for these mostly young patients,” said Shreeram 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 investigated in other complement-mediated diseases, recently achieved
positive interim results in IgA nephropathy (IgAN)10. On December 5, 2023, the FDA approved iptacopan, under the brand name
Fabhalta®, as the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH), and
it is currently being reviewed by the EMA for the same indication16-17.
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 (200 mg) in C3G patients12,15. In addition to the announced
topline results for adult patients with C3G, enrollment is ongoing in a separate cohort of adolescent patients with C3G12,15.
The study comprises a six-month double-blind period where patients were randomized 1:1 to receive iptacopan or placebo on top of background
therapy, followed by a six-month open-label period where all patients receive iptacopan (including those who were previously on placebo)
on top of background therapy12,15.
The primary endpoint for the 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 at 12 months (both treatment arms) and a comparison between proteinuria reduction at 6 and 12 months (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 (as measured by disease
total activity score in a renal biopsy), change in patient reported fatigue (as measured by FACIT-Fatigue score), and safety and tolerability12,15.
About C3G
C3 glomerulopathy (C3G) is an ultra-rare, progressive complement-mediated kidney disease that initially
presents in mostly children and young adults4-6,18. Each year, approximately 1-2 people per million worldwide are newly diagnosed
with C3G, a form of membranoproliferative glomerulonephritis (MPGN)4.
In C3G, overactivation of the alternative complement pathway – part of the immune system –
causes deposits of C3 protein to build up in kidney glomeruli (a network 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 in urine), hematuria
(blood in urine) and reduced kidney function4,7,18-20. Approximately 50% of C3G patients progress to kidney failure within
10 years of diagnosis, at which point they will require dialysis and/or kidney transplantation6-7, with over 55% of patients with
C3G experiencing disease recurrence post-transplant21-24.
About iptacopan
Iptacopan is an oral, Factor B inhibitor of the alternative complement pathway17.
Discovered at Novartis, iptacopan recently demonstrated clinically
meaningful and highly statistically significant proteinuria reduction in patients with IgA 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 membranoproliferative glomerulonephritis (IC-MPGN) (APPARENT [NCT05755386])13-14. On December 5, 2023, the
FDA approved iptacopan, under the brand name Fabhalta®, as the first oral monotherapy for the treatment of adults with
paroxysmal nocturnal hemoglobinuria (PNH), and it is currently being reviewed by the EMA for the same indication16-17.
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, requiring maintenance dialysis and/or kidney transplantation30-31.
At Novartis, our mission in nephrology began 40 years ago with transplantation and immunosuppression.
Our commitment continues today through our aim to transform the lives of people living with kidney diseases by investigating 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,” “investigational,” “progressing,”
“development,” “upcoming,” “ongoing,” “aim,” or similar terms, or by express or implied
discussions regarding potential marketing approvals, new indications or labeling for iptacopan, or regarding potential future revenues
from iptacopan. 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 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 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 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 an innovative medicines company. Every day, we work to reimagine medicine to improve
and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease.
Our medicines reach more than 250 million people worldwide.
Reimagine medicine with us: Visit us
at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter
and Instagram.
References
| 2. | Novartis iptacopan meets primary endpoints
in Phase II study in rare kidney disease C3 glomerulopathy (C3G). Novartis. Accessed December
6, 2023. 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 C3 Glomerulopathy. Kidney Int Rep. 2023;8:2754-2764. |
| 4. | Schena
FP, Esposito P, Rossini M. A Narrative Review on C3 Glomerulopathy:
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. C3 Glomerulopathy. GeneReviews®
[Internet]. Updated 2018. University of Washington, Seattle; 1993-2022. |
| 7. | Smith
RJH, Appel GB, Blom AM, et al. C3 Glomerulopathy –
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 C3 Glomerulopathy: Conclusions from a “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 highly statistically
significant proteinuria reduction in patients with IgA nephropathy (IgAN). Novartis. Accessed
December 6, 2023. https://www.novartis.com/news/media-releases/novartis-investigational-iptacopan-phase-iii-study-demonstrates-clinically-meaningful-and-highly-statistically-significant-proteinuria-reduction-patients-iga-nephropathy-igan |
| 11. | Novartis
Pharmaceuticals. Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
(APPLAUSE-IgAN). clinicaltrials.gov. Accessed December 6, 2023. https://clinicaltrials.gov/study/NCT04578834 |
| 12. | Novartis
Pharmaceuticals. Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy.
(APPEAR-C3G). clinicaltrials.gov. Accessed December 6, 2023. https://clinicaltrials.gov/study/NCT04817618 |
| 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.
Accessed December 6, 2023. https://clinicaltrials.gov/study/NCT04889430 |
| 14. | Novartis
Pharmaceuticals. Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN (APPARENT).
clinicaltrials.gov. Accessed December 6, 2023. https://clinicaltrials.gov/study/NCT05755386 |
| 15. | Bomback
AS, Kavanagh D, Vivarelli M, et al. Alternative Complement Pathway Inhibition With Iptacopan
for the Treatment of C3 Glomerulopathy-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. Accessed December 6, 2023. 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; December 2023. |
| 18. | Medjeral-Thomas NR,
O'Shaughnessy MM, O'Regan JA, et al. C3 Glomerulopathy:
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. C3 Glomerulopathy 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 C3 Glomerulopathy:
A Complement-Mediated Disease. Nephron. 2020;144(6):272-280. |
| 21. | Servais A, Noël
LH, Roumenina LT, et al. Acquired and Genetic Complement
Abnormalities Play a Critical Role in Dense Deposit Disease and Other C3 Glomerulopathies.
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
C3 Glomerulopathy: 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. Accessed December 6, 2023. 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. Accessed December 6, 2023. 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) in C3 glomerulopathy (C3G). Novartis. Accessed
December 6, 2023. 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. Accessed December 6, 2023. https://www.kidney.org/kidneydisease/global-facts-about-kidney-disease |
| 30. | NHS.
Kidney Disease. Accessed December 6, 2023. https://www.nhs.uk/conditions/kidney-disease/ |
| 31. | National
Kidney Foundation. Chronic kidney disease (CKD). Accessed December 6, 2023. https://www.kidney.org/atoz/content/about-chronic-kidney-disease |
# # #
Novartis Media Relations
E-mail: media.relations@novartis.com
|
|
|
Central |
|
North America |
|
Richard Jarvis |
+41 79 584 2326 |
Julie Masow |
+1 862 579 8456 |
Anja von Treskow
Anna Schäfers |
+41 79 392 9697
+41 79 801 7267 |
Michael Meo
Marlena Abdinoor |
+1 862 274 5414
+1 617 335 9525 |
Switzerland
Satoshi Sugimoto |
+41 79 619 2035 |
|
|
|
|
|
|
Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations@novartis.com
|
|
Central |
|
North America |
|
Samir Shah |
+41 61 324 7944 |
Sloan Simpson |
+1 862 345 4440 |
Nicole Zinsli-Somm |
+41 61 324 3809 |
Parag Mahanti |
+1 973 876 4912 |
Isabella Zinck |
+41 61 324 7188 |
Jonathan Graham |
+1 201 602 9921 |
Imke Kappes |
+41 61 324 82 69 |
|
|
Zain Iqbal |
+41 61 324 03 90 |
|
|
SIGNATURES
Pursuant to the requirements
of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto
duly authorized.
|
Novartis AG |
|
|
|
|
|
|
|
|
|
Date: December 11, 2023 |
By: |
/s/ PAUL PENEPENT |
|
|
Name: |
Paul Penepent |
|
|
Title: |
Head Group Financial Reporting and Accounting |
Novartis (NYSE:NVS)
Historical Stock Chart
From Sep 2024 to Oct 2024
Novartis (NYSE:NVS)
Historical Stock Chart
From Oct 2023 to Oct 2024