Novartis Reports 2023 Full-Year Results: Global Net Sales Reach $45.44 Billion, Driven by 261% Surge in Pluvicto Revenue

Jan 31, 2024 15:46 CST Updated 15:46

Novartis

Drug Development and Manufacturing

Author｜Gray Rabbit

On January 31, Novartis released its 2023 annual report, showing global net sales of $45.44 billion in 2023, a year-on-year increase of 10%. The sales growth was mainly driven by the continued strong performance of Entresto (+31% cc), Kesimpta (+99% cc), Kisqali (+75% cc), Pluvicto (+261% cc), and Scemblix (+179% cc).Net sales in the fourth quarter reached US$11.423 billion, increasing by 10%, with core operating income growing by 13%.

Good News Keeps Coming in the Field of Nephrology

In August 2023, Novartis completed the acquisition of Chinook Therapeutics for a $3.2 billion upfront payment,In January 2024, Novartis fully acquired SinpharNovartis Pharmaceuticals, a biotechnology company co-founded by Chinook Therapeutics and several internationally leading life science investors in December 2021, to accelerate its strategic expansion in the field of kidney diseases.

Novartis Acquires Chinook, Obtaining Two IgA Nephropathy (IgAN) Assets in Phase III Studies:Oral endothelin A receptor antagonist atrasentan and anti-APRIL monoclonal antibody zigakibart, the acquisition of SignalChem Pharmaceuticals has gained its two core assets in Greater China and Singapore, includingAtrasentan (Phase 3) and BION-1301 (Phase 2)In addition, Novartis has another drug in the field of nephrology.iptacopan(Figure 1) [1].

Figure1. Novartis' Pipeline Layout in the Field of Nephrology

On December 6, 2023, Novartis announced that the complement B factor inhibitor iptacopan had been approved by the FDA for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH), becoming the first oral monotherapy for PNH.[2]。

This approval is based on the Phase III APPLY-PNH trial, which targeted patients with residual anemia (hemoglobin < 10 g/dL) who, despite prior treatment with anti-C5 therapy, switched to iptacopan.Patients showed improved hemoglobin levels and a higher transfusion avoidance rate without red blood cell transfusions compared to those who continued anti-C5 treatment.. The Phase III APPOINT-PNH study conducted in complement inhibitor-naïve patients also supported this approval.

On December 11, 2023, Novartis announcediLong-term results of the pivotal Phase III APPLY-PNH trial of iptacopan in adult patients with PNH: Continuous treatment with iptacopan (200 mg, twice daily) for 48 weeks.Continuously increase hemoglobin levels to near-normal levels (12 g/dL or higher), avoid transfusions, and reduce fatigue reported by most patients., in the extension, patients switching from anti-C5 therapy to iptacopan treatment showed similar benefits [3].

Except for PNH,Iptacopan is also currently in the critical research phase for many other complement-mediated diseases (CMD), including C3 glomerulopathy (C3G) and IgA nephropathy.（IgAN）、Lupus Nephritis（LN）and Cold Agglutinin Disease（CAD）et al. (Figure 2) [4]。

Figure 2. Iptacopan Indication Layout

2023Year10Month2On [date], Novartis announcediptacopanOfIIIPeriodAPPLAUSE-IgANResearch（NCT04578834) in9Pre-specified at the monthPositive Topline Results Achieved in Interim Analysis. The study continued in a double-blind manner by measuring 24 Estimated glomerular filtration rate within months (eGFR) Slope to evaluateiptacopan Slow downIgAN The ability to progress, which is the primary endpoint at the end of the study, is expected to2025 Top-line results obtained in (Figure3）[5]。

Figure 3. APPLAUSE-IgAN Study Results

On December 11, 2023, Novartis announced the six-month double-blind trial of iptacopan for the treatment of patients with C3 glomerulopathy.Positive Topline Results from Phase III APPEAR-C3G Study. The study met its primary endpoint, with iptacopan (200 mg, twice daily) showing clinical and statistical significance in reducing proteinuria compared to placebo, and the safety profile of iptacopan was consistent with previously reported data [6].

Besides iptacopan,Atrasentan in IgAN Patients: NCT04573478 Clinical Interim Analysis Also Yields Positive Results - The study achieved its primary efficacy endpoint in the 36-week interim analysis.Atrasentan demonstrated superiority over placebo in IgAN patients receiving supportive care (maximum tolerated and stable doses of renin-angiotensin system [RAS] inhibitors).Proteinuria was clinically meaningful and highly statistically significant reducedBased on the results of this interim proteinuria endpoint analysis, Novartis plans to submit an application in 2024 to accelerate approval in the United States [7].

$4.165 Billion: Novartis Expands Small Nucleic Acid Pipeline

On January 7, 2024, Novartis entered into two exclusive license cooperation agreements with Bowang Pharmaceutical for RNAi therapies.Two products developed for cardiovascular diseases have been globally licensed to Novartis, excluding Greater China.The total potential value of the deal is up to 4.165 billion US dollars. In addition, Novartis will also obtain the option for up to 2 additional target compounds for cardiovascular diseases (Figure 4).

Figure 4. Part of the R&D pipeline of Bowang Pharmaceutical

Nucleic acid drugs can be divided intomRNATwo types of drugs: small molecule drugs and small nucleic acid drugs. Small nucleic acid drugs are short-chain nucleic acids composed of a small number of nucleotides, which achieve the purpose of treating diseases by interfering with the expression of target genes. Among the types of small nucleic acid drugs,Antisense oligonucleotide (ASO) and small interferenceRNA（siRNA) Two typesThe most studied.

Previously, mRNA drugs gained significant attention due to COVID-19, while small nucleic acid drugs were largely overlooked,Recently, small nucleic acid drugs have掀起一阵风, and Novartis' deal has pushed the small nucleic acid field to a climax.

Early small nucleic acid drugs existedEasy to be degraded by nucleases, high renal clearance, and significant off-target effectsand other issues progressed slowly, but later withImprovements in Small Nucleic Acid Chemical Modifications and Delivery Technologies, small nucleic acid drugs have flourished.

Compared with small molecule or antibody drugs, small nucleic acid drugs directly targetDNAOrRNA，ToolWith advantages such as a rich pool of candidate targets, short R&D cycles, and high clinical development success rates.。

As of now, there are 17 approved small nucleic acid drugs globally (including those that have been withdrawn from the market), 80% of which were approved for marketing after 2016, including Novartis' drug Leqvio for treating hyperlipidemia.。

Leqvio is a long-acting lipid-lowering siRNA drug targeting PCSK9 that Novartis acquired in December 2020 for $9.7 billion through the acquisition of The Medicine Company. It was successively approved for marketing in the United States in December 2021 and in China in August 2023.YesThe World's First Approved Small Nucleic Acid Drug for Treating Common Chronic Diseases, breaking the limitation that small nucleic acid drugs can only treat rare diseases.

Compared with the approved PCSK9 monoclonal antibody drugs alirocumab and evolocumab,The advantage of Leqvio lies in its dosing frequency; after the initial dose and the dose at the third month, subsequent doses are only required once every six months., significantly reducing the frequency of administration and increasing patient compliance. Since its launch, Leqvio's sales have risen sharply,Leqvio Sales Increased by 217% in 2023, Reaching $355 Million (Figure5）[8]。

Figure 5. Sales of Leqvio

Lutathera and Pluvicto Lead the Nuclear Medicine Craze

Nuclear medicine, also known as radiotherapy, is a classSpecial drugs containing radionuclides for medical diagnosis or treatment, composed of a combination of radioactive isotopes and organic molecular bonds.

Radiopharmaceuticals are mainly divided into two categories: diagnostic radiopharmaceuticals and therapeutic radiopharmaceuticals. Previously, the main type used in the market was diagnostic radiopharmaceuticals.Until January 26, 2018, the market rule was broken when Novartis' radiopharmaceutical (RDC) Lutathera, used for treating patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors, was launched.。

LutatheraByFDAThe approval is based onNETTER-1（NCT01578239) Test results, a randomized, multi-center, open-label, active-controlled trial involving229Progressive, Well-differentiated, Locally Advanced/Patients with inoperable or metastatic somatostatin receptor-positive midgut carcinoid tumors.

The research results show that:LutatheraThe group did not reach the median progression-free survival (PFS), the high-dose long-acting octreotide group was8.5Months[9]。

On September 25, 2023, Novartis announced the Lutathera group'sPhase III NETTER-2 Trial Meets Primary EndpointCompared with high-dose long-acting octreotide alone, Lutathera combined with long-acting octreotide as first-line treatment significantly improved PFS in newly diagnosed SSTR-positive, grade 2 and 3 advanced gastroenteropancreatic neuroendocrine tumors (GEP-NET) (Figure 6) [10].

Figure 6. NETTER-2 Trial Design and Results

LutatheraIn the first year of listing, the revenue reached1.67Billion US dollars,2019Annual growth to4.41Billion US dollars,2022Annual revenue is4.71Billion US dollars,Sales revenue grew to US$605 million in 2023, increasing by 28% year-on-year [8].

Except forLutathera，Novartis also has a blockbuster RDC drug, Pluvicto, which was approved for marketing by the FDA on March 23, 2022, for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).

2016Since the year,FDAApproved11PaymentRDCDrug, of which only2For therapeutic useRDC, namely NovartisLutatheraAndPluvicto, which also laid the foundation forNovartis inRDCFieldTheAbsolute Leadership Position[11]。

PluvictoFFDA ApprovalYesBased on the VISION (NCT03511664) trial results, this was a randomized (2:1), multicenter, open-label trial evaluating Pluvicto in combination with the best standard of care (BSoC) (n=551) or BSoC alone (n=280) for the treatment of men with progressive PSMA-positive mCRPC.

The trial results showed that: Pluvicto group had statistically significant improvements in the primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS). The OS hazard ratio (HR) for Pluvicto plus BSoC versus BSoC was 0.62 (95% CI: 0.52, 0.74).；p<0.001）。The median OS for the Pluvicto plus BSoC group was 15.3 months, while the median OS for the BSoC group was 11.3 months.[12]。

At the 2023 European Society for Medical Oncology (ESMO) Congress, Novartis presented the data from the Phase III PSMAfore trial of Pluvicto: Compared with the androgen receptor pathway inhibitor (ARPI) treatment group, the Pluvicto group achieved its primary endpoint, showing clinical and statistical significance in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC).[13]。

Figure 7. Results of the PSMAfore Trial

PluvictoShowed more thanLutatheraStronger sales explosiveness, achieved in the year of listing2.7Billion USD in sales,Total sales in 2023 reached $9.8 billion, a year-on-year increase of 261% (Figure 8) [8].

Figure 8. Sales of Pluvicto

Summary

In 2023, Novartis underwent a major business adjustment.Novartis spun off its generics business, Sandoz, becoming a company fully dedicated to innovative drugs.See details:Sandoz officially goes public independently, will it become the leader in generic drugs in the future?

Novartis stated that it will focus onFour core therapeutic areas, including cardiovascular-Kidney-Metabolism (CRM), Immunology, Neuroscience, Oncology，Build“2+3”Technology platforms, respectively for chemistry, biologics,xRNA, radioligands, and cell and gene therapies, providing high-value medicines to alleviate the greatest disease burdens on society through technological leadership in research and development as well as new approaches to access.See details:Novartis Cuts 10% of R&D Pipeline: Including Highly Anticipated Star Projects

Main References

1.Novartis Strategy & Growth Update Vas Narasimhan, CEO J.P. Morgan Healthcare Conference

2.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

3.Novartis presents new 48-week results from Phase III APPLY-PNH trial showing sustained efficacy and long-term safety of Fabhalta® (iptacopan) in adults with paroxysmal nocturnal hemoglobinuria (PNH)

4.novartis Q3 2023 Results Investor presentation

5.Novartis investigational iptacopan Phase III study demonstrates clinically meaningful and highly statistically significant proteinuria reduction in patients with IgA nephropathy (IgAN)

6.Novartis investigational iptacopan Phase III study demonstrates clinically meaningful and statistically significant proteinuria reduction in patients with C3 glomerulopathy (C3G)

7.Novartis investigational atrasentan Phase III study demonstrates clinically meaningful and highly statistically significant proteinuria reduction in patients with IgA nephropathy (IgAN)

8.Q4 2023 results Investor presentation January 31, 2024

9.FDA approves lutetium Lu 177 dotatate for treatment of GEP-NETS

10.Novartis radioligand therapy Lutathera® demonstrated statistically significant and clinically meaningful progression-free survival in first line advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

11.BiG Biomedical Innovation Community: Radiopharmaceuticals: Past and Present, Market Size, Access Barriers, R&D Hotspots

12.FDA approves Pluvicto for metastatic castration-resistant prostate cancer

13.Novartis Pluvicto™ shows clinically meaningful and highly statistically significant rPFS benefit in patients with PSMA-positive metastatic castration-resistant prostate cancer in the pre-taxane setting

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