S1PR1 modulators(Sphingosine 1-phosphate receptor Edg-1 modulators), S1PR5 modulators(Sphingosine 1-phosphate receptor Edg-8 modulators), S1PRs modulators(Sphingosine 1-phosphate receptor modulators)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesOther Diseases

Active Indication

Multiple Sclerosis, Secondary ProgressiveMultiple SclerosisAlzheimer Disease+ [1]

Inactive Indication

Cerebral HemorrhageDermatomyositisHemorrhagic stroke+ [5]

Originator Organization

Novartis Pharma AG

Active Organization

Novartis Pharmaceuticals Corp.Novartis Europharm Ltd.

Novartis Pharma KK

+ [4]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (26 Mar 2019),

Multiple Sclerosis

RegulationSpecial Review Project (CN), Orphan Drug (US), Priority Review (CN)

Structure

Molecular FormulaC33H39F3N2O7

InChIKeyGDOJWCQYEGMSSF-FLNKEUCSSA-N

CAS Registry1234627-85-0

Clinical Trials associated with Siponimod Fumaric Acid

NCT06639282 / Not yet recruitingPhase 2IIT

SIPO1-AD: a Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients with Mild Alzheimer&#39;s Disease Dementia

Collaboration with multiple sclerosis (MS) specialty colleagues led us to formulate the central hypothesis that Siponimod could lower the rate of brain atrophy in Alzheimer's disease (AD) subjects. To test our central hypothesis, we will carry out an 18-month Phase II, double-blind, randomized, twoarmed, placebo controlled, proof-of-concept clinical study in early AD subjects (i.e. mild AD) who will be receiving an escalating dose of Siponimod or placebo in the ratio 2:1 for 12 months, followed by a 6-month washout period. The primary outcome measures are safety and tolerability of Siponimod in mild AD subjects. The secondary outcome measures are the rates of brain atrophy derived from volumetric MRI (vMRI) as a proxy for neurodegeneration conducted at baseline, 6, 12, and 18 months. The tertiary outcome measures are the changes in cognition and the levels of AD-associated (e.g., Aβ and tau) and inflammatory biomarkers in CSF after Siponimod exposure. In an exploratory effort, we will also measure plasma inflammatory markers during the entire duration of the study to investigate whether one or more of these markers can be used as dynamic surrogate markers of treatment response. Using our unique experience with the repurposing of immunomodulatory drugs for AD (and NCT #04032626), in the present project we are using elements of clinical trial design that we believe were successful and made some adjustments to fit the pharmacologic and toxic properties of Siponimod.

Start Date01 Nov 2024

Sponsor / Collaborator

St. Joseph's Medical Center, Inc.

[+5]

CTR20232992 / CompletedNot Applicable

西尼莫德片的人体生物等效性研究

[Translation] Study on the bioequivalence of siponimod tablets in healthy volunteers

研究空腹/餐后状态下单次口服受试制剂西尼莫德片与参比制剂西尼莫德片（万立能®）在健康成年受试者体内的药代动力学，评价空腹/餐后状态下口服两种制剂的生物等效性和安全性。

[Translation]

The pharmacokinetics of a single oral dose of the test preparation Siponimod tablets and the reference preparation Siponimod tablets (Vanlin®) in healthy adult subjects were studied in the fasting/postprandial state, and the bioequivalence and safety of the two preparations were evaluated in the fasting/postprandial state.

Start Date23 Sep 2023

Sponsor / Collaborator

Qilu Pharmaceutical Co., Ltd.

CTR20230278 / CompletedPhase 4

一项在中国复发型多发性硬化患者中评价BAF312的有效性和安全性的回顾性、多中心真实世界研究。

[Translation] A retrospective, multicenter, real-world study evaluating the efficacy and safety of BAF312 in Chinese patients with relapsing multiple sclerosis.

1.在中国真实世界人群中，基于年复发率描述BAF312在复发型多发性硬化(RMS)患者中的有效性。 2.描述开始BAF312治疗后12个月时保持无复发的患者比例。 3.在中国真实世界人群中描述BAF312在RMS患者中的安全性特征。 4.描述开始BAF312治疗后12个月时无MRI活动性的患者比例。

[Translation]

1. Describe the efficacy of BAF312 in patients with relapsing multiple sclerosis (RMS) based on annualized relapse rate in a real-world Chinese population. 2. Describe the proportion of patients who remain relapse-free at 12 months after starting BAF312 treatment. 3. Describe the safety profile of BAF312 in patients with RMS in a real-world Chinese population. 4. Describe the proportion of patients with no MRI activity at 12 months after starting BAF312 treatment.

Start Date23 Apr 2023

Sponsor / Collaborator

Novartis Farmacéutica SA

[+3]

100 Clinical Results associated with Siponimod Fumaric Acid

100 Translational Medicine associated with Siponimod Fumaric Acid

100 Patents (Medical) associated with Siponimod Fumaric Acid

266

Literatures (Medical) associated with Siponimod Fumaric Acid

01 Dec 2024·American Journal of Ophthalmology Case Reports

Siponimod-associated cystoid macular edema without known risk factors

Article

Author: Kim, Min Young ; Smith, Stephen J ; Liao, Yaping Joyce ; Alkhabaz, Anas

PurposeThis case report highlights the importance of monitoring ocular health for patients starting on siponimod treatment, a sphingosine-1-phosphate receptor modulator, for relapsing-remitting multiple sclerosis. By showing how medication adverse events present in patients, we can revisit the current guidelines on ophthalmic evaluation recommendations.ObservationsWe report a 60-year-old patient who presented with unilateral blurry vision upon initiating siponimod therapy for the treatment of relapsing-remitting multiple sclerosis. Her exam findings did not show visual field defects but were significant for cystoid macular edema distorting the foveal contour. Upon stopping siponimod therapy, the patient's macular edema and symptoms resolved significantly within 7 days and completely resolved 1 month later.Conclusions and importanceThis case showcases siponimod-associated cystoid macular edema in a patient without known risk factors, such as diabetes mellitus and uveitis. The patient also had the earliest reported symptom onset to date following the initiation of siponimod therapy. Current recommendations from the American Academy of Ophthalmology and FDA stress the importance of ophthalmic evaluation three to four months after treatment initiation for patients with a history of risk factors. Given our current case and its comparison with four previously reported cases, we recommend that physicians inform patients of possible ocular adverse events with siponimod therapy regardless of their past medical history and duration of treatment.

01 Nov 2024·PharmacoEconomics - Open

Clinicians’ Preferences for Sphingosine-1-Phosphate Receptor Modulators in Multiple Sclerosis Based on Clinical Management Considerations: A Choice Experiment

Article

Author: Quaife, Matt ; Turner, Vicky ; Kern, David M ; Keenan, Alexander ; Le, Hoa H ; Fernandez, Gabriela S ; Das, Anup ; Whichello, Chiara ; Ross, Amy Perrin

BACKGROUNDFour sphingosine-1-phosphate receptor (S1PR) modulators are currently available in the USA for treating relapsing forms of multiple sclerosis (MS). These S1PR modulators have similar efficacy. Clinicians may therefore consider other factors, such as clinical management considerations, when distinguishing among treatments. This study estimated which S1PR modulator clinicians would choose on the basis of a treatment's clinical management and quantified how individual aspects of clinical management might drive this choice.METHODSA multi-criteria decision analysis (MCDA) was conducted on the basis of clinical management preferences elicited in a discrete choice experiment (DCE) and real-world clinical management profiles of the S1PR modulators currently available to treat relapsing forms of MS (fingolimod, ozanimod, ponesimod, siponimod). The DCE was completed by neurologists in the USA experienced in treating MS and included eight clinical management attributes: first-dose observations, genotyping, liver function tests, eye exams, drug-drug interactions, interactions with antidepressants, interactions with foods high in tyramine, and immune system recovery time. Attribute levels were selected on the basis of S1PR modulator product labels. In the MCDA, partial MCDA scores were created for each attribute and summed to produce an overall MCDA score for each S1PR modulator.RESULTSThe DCE was completed by 200 neurologists. The overall MCDA score was highest for ponesimod (4.78 points), followed by siponimod (4.10 points), fingolimod (3.61 points), and ozanimod (2.38 points). Having fewer drug-drug interactions contributed most to the overall scores (up to 1.56 points), followed by having no first-dose observations (0.95 points), the shortest immune system recovery time (0.94 points), and not interacting with foods high in tyramine (0.86 points).CONCLUSIONWhen considering clinical management convenience, the average US-based neurologist treating MS is likely to choose ponesimod over siponimod, fingolimod, or ozanimod. The strongest driver of preferences was the number of drug-drug interactions. This information can help inform recommendations for the treatment of MS and facilitate shared decision-making between clinicians and patients.

01 Nov 2024·The Patient - Patient-Centered Outcomes Research

Patients’ Preferences for Sphingosine-1-Phosphate Receptor Modulators in Multiple Sclerosis Based on Clinical Management Considerations: A Choice Experiment

Article

Author: Turner, Vicky ; Kern, David M ; Keenan, Alexander ; Quaife, Matthew ; Le, Hoa H ; Fernandez, Gabriela S ; Das, Anup ; Whichello, Chiara ; Ross, Amy Perrin

BACKGROUNDSeveral sphingosine-1-phosphate receptor (S1PR) modulators are available in the US for treating relapsing forms of multiple sclerosis (RMS). Given that these S1PR modulators have similar efficacy and safety, patients may consider the clinical management characteristics of the S1PR modulators when deciding among treatments. However, none of the S1PR modulators is clearly superior in every aspect of clinical management, and for some treatments, clinical management varies based on a patient's comorbid health conditions (e.g., heart conditions [HC]).OBJECTIVESThis study aimed to determine which S1PR modulator patients with relapsing-remitting multiple sclerosis (RRMS) would prefer based on clinical management considerations, and to estimate how different clinical management considerations might drive these preferences. Preferences were explored separately for patients with and without comorbid HC.METHODSA multicriteria decision analysis was conducted on S1PR modulators approved to treat RMS: fingolimod, ozanimod, siponimod, and ponesimod. Clinical management preferences of patients with RRMS were elicited in a discrete choice experiment (DCE) in which participants repeatedly chose between hypothetical S1PR modulator profiles based on their clinical management attributes. Attributes included first-dose observations, genotyping, liver function tests, eye examinations, drug-drug interactions, interactions with antidepressants, interactions with foods high in tyramine, and immune system recovery time. Preferences were estimated separately for patients with HC and without HC (noHC). Marginal utilities were calculated from the DCE data for each attribute and level using a mixed logit model. In the multicriteria decision analysis, partial value scores were created by applying the marginal utilities for each attribute and level to the real-world profiles of S1PR modulators. Partial value scores were summed to determine an overall clinical management value score for each S1PR modulator.RESULTSFour hundred patients with RRMS completed the DCE. Ponesimod had the highest overall value score for patients both without (n = 341) and with (n = 59) HC (noHC: 5.1; HC: 4.0), followed by siponimod (noHC: 4.9; HC: 3.3), fingolimod (noHC: 3.4; HC: 2.8), and ozanimod (noHC: 0.9; HC: 0.8). Overall, immune system recovery time contributed the highest partial value scores (noHC: up to 1.9 points; HC: up to 1.2 points), followed by the number of drug-drug interactions (noHC: up to 1.2 points; HC: up to 1.7 points).CONCLUSIONSWhen considering the clinical management of S1PR modulators, the average patient with RRMS is expected to choose a treatment with shorter immune system recovery time and fewer interactions with other drugs. Patients both with and without heart conditions are likely to prefer the clinical management profile of ponesimod over those of siponimod, fingolimod, and ozanimod. This information can help inform recommendations for treating RRMS and facilitate shared decision making between patients and their doctors.

News (Medical) associated with Siponimod Fumaric Acid

07 Dec 2023

·www.prnewswire.com

Vanda Pharmaceuticals Acquires U.S. and Canadian Rights to PONVORY® (ponesimod), a Selective S1P1R Modulator Approved for Patients with Relapsing Multiple Sclerosis

WASHINGTON, Dec. 7, 2023 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced that it has acquired U.S. and Canadian rights to PONVORY® (ponesimod) from Actelion Pharmaceuticals Ltd. (Janssen), a Johnson & Johnson Company. PONVORY® is approved by the U.S. Food and Drug Administration (FDA) and Health Canada to treat adults with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. PONVORY® has a proven safety profile with over 10 years of data. "The acquisition of Ponvory is a significant milestone for Vanda, as it expands our commercial portfolio and gives us access to a versatile immune response modifier that can potentially have broad application in treating a number of autoimmune-based disorders," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. In a clinical study, PONVORY® was shown to be superior to Aubagio®, another approved drug for multiple sclerosis (MS), in the annual rate of relapse and it was also associated with fewer T2 and T1 MRI lesions versus the comparator. Approximately 9 out of 10 people taking PONVORY® did not experience disability progression over 2 years (as measured by the time to 3-month Confirmed Disability Progression).1 The effect of PONVORY® on the decrease of circulating lymphocytes is reversible so lymphocytes quickly return to baseline levels after discontinuation of PONVORY®. This rapid reversible effect is important for people needing to pause therapy for a vaccine. For women of childbearing age who want to become pregnant, PONVORY® is eliminated from the body in about 7 days after stopping treatment. The mechanism of action of PONVORY® makes it also a potential therapeutic candidate for the treatment of a diverse group of inflammatory/autoimmune disorders ranging from psoriasis to ulcerative colitis. In a randomized placebo controlled clinical study, PONVORY® has also been shown to reduce the symptoms and signs of psoriasis.2 Under the terms of the agreement, Vanda paid $100 million to acquire the U.S. and Canadian rights to PONVORY®. Janssen will continue to operate the business pursuant to a Transitional Business License Agreement, during which time, Vanda and Janssen will transition regulatory and supply responsibility for PONVORY® to Vanda. Stifel acted as exclusive financial advisor to Vanda with respect to this acquisition. About PONVORY® PONVORY® (ponesimod) is a daily oral selective sphingosine-1-phosphate receptor 1 (S1P1R) modulator, indicated to treat adults with relapsing forms of MS, to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. PONVORY® blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. PONVORY® does not require genetic testing or first-dose cardiac monitoring for most patients. Because initiation of PONVORY® treatment results in a decrease in heart rate, first-dose monitoring is recommended in patients with certain preexisting cardiac conditions. For full U.S. Prescribing Information for PONVORY®, including Important Safety Information, visit . The PONVORY® Orange Book listed patent with the latest expiry date is set to expire in December 2035. About Multiple Sclerosis MS is a chronic autoimmune inflammatory disease of the central nervous system (CNS) in which immune cells attack myelin (the protective casing that insulates nerve cells), damaging or destroying it and causing inflammation. This affects how the CNS processes information and communicates with the rest of the body, causing the neurologic signs and symptoms of MS. Symptoms vary by person, but common symptoms include fatigue, balance and walking problems, numbness or tingling, dizziness and vertigo, vision problems, bladder and bowel problems and weakness. About Sphingosine-1-Phosphate Receptor 1 Modulators PONVORY® (ponesimod) belongs in the molecular class of sphingosine-1-phosphate (S1P) analogs that act as modulators of the S1P receptor (S1PR). There are five S1PR (1-5) subtypes with different tissue distribution and functional specificity. PONVORY® is a selective ligand for the S1P1R subtype. It has been speculated that selectivity for S1P1R, rapid onset and reversibility of pharmacological effects, and an optimized titration regimen may differentiate ponesimod from fingolimod, the first of the oral S1PR modulators in the treatment of multiple sclerosis, and may lead to better safety and tolerability.3 Besides fingolimod (FDA approved in 2010), there are four additional FDA-approved members in the S1P modulator class that include siponimod (2019), ozanimod (2020), ponesimod (2021) and etrasimod (2023). With the exception of etrasimod, all other drugs are currently approved for the treatment of MS. Ozanimod and etrasimod are approved for the treatment of ulcerative colitis. The S1PR modulators act by preventing the egress of lymphocytes from the lymph nodes and as such reduce the number of circulating lymphocytes leading to a decrease of the autoimmune response at the target site. Based on the latest Datamonitor market forecasts for multiple sclerosis and ulcerative colitis, the S1P market in the U.S. is expected to be approximately $2 billion in 2024 and to grow to approximately $3.5 billion in 2028.4 References Kappos L., Fox RJ., Burcklen M. (2021). Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial. JAMA neurology, 78(5), 558–567. Vaclavkova, A., Chimenti, S., Arenberger, P., Holló, P., Sator, P. G., Burcklen, M., Stefani, M., & D'Ambrosio, D. (2014). Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet (London, England), 384(9959), 2036–2045. (14)60803-5 D'Ambrosio, D., Freedman, M. S., & Prinz, J. (2016). Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases. Therapeutic advances in chronic disease, 7(1), 18–33. Datamonitor Healthcare – Multiple Sclerosis (MS) Patient-Based Market Forecast published October 2023 and Datamonitor Healthcare – Ulcerative Colitis Patient-Based Market Forecast published March 2023. About Vanda Pharmaceuticals Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit and follow us on X @vandapharma. CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS Various statements in this press release, including, but not limited to statements regarding the impact that the acquisition of PONVORY® will have on Vanda's commercial portfolio, the potential of PONVORY® to treat a diverse group of inflammatory/autoimmune disorders, the post-closing transitional plans to operate the U.S. and Canadian PONVORY® business during the transition period, the parties' plans to transition regulatory and supply responsibility for PONVORY® to Vanda, the duration of the patent protection for PONVORY®, the potential differentiation of PONVORY® from other drugs in its class, the safety and tolerability of PONVORY®, and the size and growth of the potential U.S. market for the class of S1P1R modulators are "forward-looking statements" under the securities laws. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Forward-looking statements are based upon current expectations and assumptions that involve risks, changes in circumstances and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, Vanda's ability to successfully commercialize PONVORY®, the results of any clinical trials conducted for PONVORY® in the treatment of other inflammatory/autoimmune disorders and Vanda's ability to obtain regulatory approval of PONVORY® for any such additional indications, the seller's ability to effectively operate the U.S. and Canadian PONVORY® business during the transition period, the parties' ability to transition regulatory and supply responsibility for PONVORY® to Vanda, the ability of the parties to successfully defend any challenge to the PONVORY® patents, the ability of the identified characteristics of PONVORY® and an optimized titration regimen to differentiate it from other drugs in its class and result in better safety and tolerability, and the market acceptance and commercial success of S1P1R modulators. Therefore, no assurance can be given that the results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Forward-looking statements in this press release should be evaluated together with the various risks and uncertainties that affect Vanda's business and market, particularly those identified in the "Cautionary Note Regarding Forward-Looking Statements", "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's most recent Annual Report on Form 10-K, as updated by Vanda's subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the U.S. Securities and Exchange Commission, which are available at . All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this Current Report on Form 8-K is provided only as of the date of this press release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Vanda Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] SOURCE Vanda Pharmaceuticals Inc.

Drug ApprovalAcquisitionPhase 3Phase 2License out/in

20 Sep 2023

·www.fiercepharma.com

Novartis hit with another serious drug marketing breach, this time for multiple sclerosis therapy Mayzent

This marks the third instance this year in which the Prescription Medicines Code of Practice Authority has determined Novartis breached Clause 2 of the Association of the British Pharmaceutical Industry Code. The U.K. drug marketing body, the Prescription Medicines Code of Practice Authority (PMCPA), is once again taking action against Novartis' U.K. business, which has become a repeat offender in terms of "bringing discredit upon, and reducing confidence in, the pharmaceutical industry." This time, the PMCPA, responsible for policing drug marketing rules in the U.K. as outlined in the Association of the British Pharmaceutical Industry Code, identified significant concerns related to a Novartis website promoting its multiple sclerosis (MS) drug Mayzent. On the drug's official website, an anonymous healthcare professional complained to the PMCPA that Novartis had not adequately demonstrated its drug could not be used in patients who had experienced a heart attack or heart failure within the past six months, among other concerns. The PMCPA noted in its ruling that the website recommended starting treatment with Mayzent in patients with a history of myocardial infarction and heart failure “without making apparent the absolute contra-indication in patients with a history of myocardial infarction or heart failure in the previous 6 months." This was only mentioned on separate webpages and within the prescribing information, and the PMCPA said that was “insufficient” and “did not negate the misleading immediate impression given that Mayzent could be initiated in any patient with a recent history of MI or heart failure.” It added that not having this important information “might potentially prejudice patient safety.” Due to the gravity of this safety concern, the PMCPA determined that Novartis had violated Clause 2 of the code, which is the most severe breach and involves a company "bringing discredit upon, and reducing confidence in, the pharmaceutical industry." The healthcare professional went one step further, saying Novartis’ compliance culture was poor and that there were “huge errors around compliance” and that a “lack of experienced signatories was [detrimental] to a safe compliance speak up culture.” Novartis argued against this accusation in its case to the PMCPA, and the panel did not factor this into its ruling. But Novartis has been on the PMCPA’s naughty list many times this year, including now three times for breaching Clause 2, which is only reserved for the most serious of cases. This includes a similar case involving its heart drug Entresto, where, earlier this year, Novartis was found in breach for failing to provide all of the drug's safety risks on a website intended for healthcare professionals. Novartis also received a reprimand for another Clause 2 breach, once again related to Entresto. This time, the issue concerned a podcast titled "Heart to Heart," developed specifically for heart failure specialist nurses. In one of the episodes, Novartis presented a series of efficacy claims and, even more significantly, safety claims that landed it in hot water. In addition to this breach, Novartis received several other separate and less serious rulings from the PMCPA. This includes yet another for Entresto, where it was found in breach of six clauses, as well as for a promotional webpage for Kesimpta, another MS drug, which fell afoul of three breaches, and another three breaches for promotional messaging on a webpage for its respiratory therapy Xolair.

01 Feb 2023

·www.globenewswire.com

Novartis continues to grow with further core margin expansion and achieves important innovation milestones

Ad hoc announcement pursuant to Art. 53 LR Full year Net sales grew +4% (cc1, -2% USD) with core operating income growing +8% (cc, 0% USD) IM sales grew +4% (cc, -2% USD) and core operating income +8% (cc, 0% USD), with IM core margin reaching 36.9% (+130 bps cc)Sandoz sales grew +4% (cc, -4% USD) with core operating income decreasing -1% (cc, -8% USD) Operating income declined -13% (cc, -21% USD), mainly due to higher restructuring and impairments. Net income declined -67% (cc, -71% USD), or -9% (cc) excluding the impact of Roche income2. Free cash flow was USD 11.9 billion (-10% USD)Core EPS was USD 6.12 +6% (cc, -3% USD); excluding Roche core income impact, core EPS grew +14% (cc) Fourth quarter Net sales grew +3% (cc, -4% USD) with core operating income growing +15% (cc, +6% USD), mainly driven by higher sales and productivity Innovative Medicines (IM) sales grew +3% (cc, -3% USD), growth drivers include: Entresto (+44% cc), Kesimpta (+157% cc), Pluvicto (reaching USD 179 million) and Kisqali (+33% cc)Sandoz sales were in line with the prior year (0% cc, -8% USD) with continued growth in biopharmaceuticals Q4 selected innovation milestones: Pluvicto Ph3 PSMAfore positive results in mCRPC; EC approval for progressive PSMA+ mCRPCIptacopan Ph3 APPLY-PNH demonstrated iptacopan superiority vs. anti-C5 in refractory PNHIptacopan Ph3 APPOINT-PNH met primary endpoint in complement inhibitor naive PNH patients Share buyback, dividend and 2023 guidance Previously announced up-to USD 15 billion share buyback ongoing; USD 4.9 billion still to be executed3Dividend of CHF 3.20 per share, an increase of 3.2%, proposed for 2022 2023 guidance4 – Group expected to grow sales low-to-mid single digit and core operating income mid single digit. IM expected to grow sales low-to-mid single digit and core operating income mid-to-high single digit Basel, February 1, 2023 - commenting on 2022 results, Vas Narasimhan, CEO of Novartis, said: “Novartis is on track to become a pure-play innovative medicines company, uniquely positioned to leverage its global scale and R&D platforms. Our six multi-billion brands5 now represent 32% of our Innovative Medicines sales and are growing 26%. Pluvicto and Scemblix had very strong launch performances, and the Leqvio launch continues to progress. Pivotal Ph3 readouts for two iptacopan studies and Pluvicto in earlier lines of therapy provide strong confidence for near to mid-term growth. Looking ahead, we have a catalyst rich pipeline with 15 pivotal readouts in the mid-term. We expect to continue to deliver improved financials and strengthen Novartis ESG foundations, on our journey to become most trusted and valued medicines company in the world”. Key figures1 Q4 2022Q4 2021% changeFY 2022FY 2021% change USD m USD mUSDccUSD mUSD mUSDccNet sales12 69013 229-4350 54551 626-24Operating income1 9492 562-24-149 19711 689-21-13Net income1 46616 306-91-906 95524 018-71-67EPS (USD)0.697.29-91-893.1910.71-70-66Free cash flow3 5523 02717 11 94513 282-10 Core operating income4 0303 81961516 66516 58808Core net income3 2513 13541413 35214 094-53Core EPS (USD)1.521.409196.126.29-36 1 Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 50 of the Condensed Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year. 2 A table showing the Q4 2022 and FY 2022 key figures excluding Roche can be found on page 8 and a reconciliation of 2021 IFRS results and non-IFRS measures core results to exclude the impacts of the 2021 divestment of our Roche investment can be found on page 58 of the Condensed Financial Report. 3 As per December 31, 2022. 4 Please see detailed guidance assumptions on page 6. 5 Potential USD sales. Strategy Update Our focus During 2022, Novartis unveiled a new focused strategy with our transformation into a “pure-play” Innovative Medicines business. We have a clear focus on five core therapeutic areas (cardiovascular, immunology, neuroscience, solid tumors and hematology), with multiple significant in-market and pipeline assets in each of these areas, that address high disease burden and have substantial growth potential. In addition to two established technology platforms (chemistry and biotherapeutics), three emerging platforms (gene & cell therapy, radioligand therapy, and xRNA) are being prioritized for continued investment into new R&D capabilities and manufacturing scale. Geographically, we are focused on growing in our priority geographies - the US, China, Germany and Japan. Our priorities Accelerate growth: Renewed attention to deliver high-value medicines (NMEs) and focus on launch excellence, with a rich pipeline across our core therapeutic areas.Deliver returns: Continuing to embed operational excellence and deliver improved financials. Novartis remains disciplined and shareholder-focused in our approach to capital allocation, with substantial cash generation and a strong capital structure supporting continued flexibility. Strengthening foundations: Unleashing the power of our people, scaling data science and technology and continuing to build trust with society. Sandoz planned spin-off The planned spin-off remains on track for H2 2023. Completion of the transaction is subject to certain conditions, including consultation with works councils and employee representatives (as required), general market conditions, tax rulings and opinions, final Board of Directors endorsement and shareholder approval in line with Swiss corporate law. The transaction is expected to be tax neutral to Novartis. Financials Fourth quarter Net sales were USD 12.7 billion (-4%, +3% cc) in the fourth quarter driven by volume growth of 10 percentage points, partly offset by price erosion of 3 percentage points and the negative impact from generic competition of 4 percentage points. Operating income was USD 1.9 billion (-24%, -14% cc), mainly due to higher restructuring costs (USD 0.6 billion), primarily related to the implementation of the previously announced streamlined organizational model. Net income was USD 1.5 billion (-91%, -90% cc), impacted by Roche income in the prior year of USD 14.6 billion. Excluding the impact of Roche income, net income grew +2% (cc). EPS was USD 0.69 (-91%, -89% cc). Excluding the impact of Roche income, EPS grew +7% (cc). Core operating income was USD 4.0 billion (+6%, +15% cc) driven by higher sales and productivity, including initial savings from the previously announced streamlined organizational model. Core operating income margin was 31.8% of net sales, increasing by 2.9 percentage points (+3.5 percentage points cc). Core net income was USD 3.3 billion (+4%, +14% cc), mainly driven by growth in core operating income, partly offset by the loss of Roche core income. Excluding the impact of Roche core income, core net income grew +17% (cc). Core EPS was USD 1.52 (+9%, +19% cc), benefiting from lower weighted average number of shares outstanding. Excluding the impact of Roche core income, core EPS grew +23% (cc). Free cash flow amounted to USD 3.6 billion (+17% USD), mainly driven by higher net cash flows from operating activities and lower purchases of intangible assets. Innovative Medicines net sales were USD 10.4 billion (-3%, +3% cc) with volume contributing 11 percentage points to growth, mainly driven by continued strong performance from Entresto, Kesimpta, Pluvicto and Kisqali. Generic competition had a negative impact of 5 percentage points, mainly due to Gilenya, Exjade and Afinitor. Pricing had a negative impact of 3 percentage points, including approximately 1 percentage point impact from a revenue deduction true-up for Cosentyx in the US, which was related to prior quarters in 2022. Sales growth for the quarter was also negatively impacted by the prior year reclassification of contract manufacturing from other revenues to sales. Excluding the contract manufacturing reclassification impact, sales would have grown +4% (cc). Sales in the US were USD 4.2 billion (+7%) and in the rest of the world USD 6.2 billion (-9%, +1% cc). Sandoz net sales were USD 2.3 billion (-8%, 0% cc) with volume contributing 5 percentage points to growth. Pricing had a negative impact of 5 percentage points. Sales in Europe were USD 1.3 billion (-7%, +3% cc), in the US USD 429 million (-10%) and in the rest of the world USD 612 million (-8%, +1% cc). Sales were negatively impacted by a prior year biopharmaceuticals contract manufacturing revenue reclassification. Excluding this impact, overall Sandoz sales would have grown +1% (cc). Global sales of Biopharmaceuticals grew to USD 517 million (-7%, +3% cc), with growth in Europe, Canada and Latin America. Full year Net sales were USD 50.5 billion (-2%, +4% cc) in the full year, driven by volume growth of 11 percentage points, partly offset by price erosion of 4 percentage points and the negative impact from generic competition of 3 percentage points. Operating income was USD 9.2 billion (-21%, -13% cc), mainly due to higher restructuring (USD 1.2 billion) primarily related to the implementation of the previously announced streamlined organizational model, higher impairments (USD 1.0 billion) and lower divestment gains (USD 0.6 billion). Net income was USD 7.0 billion (-71%, -67% cc), impacted by Roche income in the prior year. Excluding the impact of Roche income, net income declined -9% (cc). EPS was USD 3.19 (-70%, -66% cc). Excluding the impact of Roche income, EPS declined -7% (cc). Core operating income was USD 16.7 billion (0%, +8% cc) benefiting from higher sales, partly offset by higher R&D investments. Core operating income margin was 33.0% of net sales, increasing by 0.9 percentage points (+1.3 percentage points cc). Core net income was USD 13.4 billion (-5%, +3% cc) as growth in core operating income was partly offset by the loss of Roche core income. Excluding the impact of Roche core income, core net income grew +11% (cc). Core EPS was USD 6.12 (-3%, +6% cc), benefiting from lower weighted average number of shares outstanding. Excluding the impact of Roche core income, core EPS grew +14% (cc). Free cash flow amounted to USD 11.9 billion (-10% USD), mainly due to a decrease in net cash flows from operating activities and lower divestment proceeds, partly offset by lower purchases of property, plant and equipment. Innovative Medicines net sales were USD 41.3 billion (-2%, +4% cc), with volume contributing 12 percentage points to growth. Sales growth was mainly driven by continued strong growth from Entresto, Kesimpta, Kisqali, Pluvicto and Cosentyx. Generic competition had a negative impact of 4 percentage points, mainly due to Gilenya, Afinitor/Votubia and Gleevec/Glivec. Pricing had a negative impact of 4 percentage points. Sales in the US were USD 15.9 billion (+6%) and in the rest of the world USD 25.4 billion (-6%, +3% cc). Sandoz net sales were USD 9.2 billion (-4%, +4% cc) with volume contributing 10 percentage points to growth. Pricing had a negative impact of 6 percentage points. Sales in Europe were USD 4.9 billion (-7%, +4% cc), in the US USD 1.8 billion (-4%) and in the rest of the world USD 2.6 billion (+2%, +9% cc). Global sales of Biopharmaceuticals grew to USD 2.1 billion (-1%, +9% cc) across all regions. Q4 key growth drivers Underpinning our financial results in the quarter is a continued focus on key growth drivers (ranked in order of contribution to Q4 growth) including: Entresto(USD 1,291 million, +44% cc) sustained robust demand-led growth, with increased patient share across all geographiesKesimpta(USD 369 million, 157% cc) driven by strong launch uptake, access and increased demand; approved in 80 countriesPluvicto(USD 179 million, nm cc) with strong US launch performance, more than 160 active centersKisqali(USD 357 million, +33% cc) grew strongly across all geographies, based on increasing recognition of its overall survival and quality of life benefits in HR+/HER2- advanced breast cancerPromacta/Revolade(USD 540 million, +11% cc) showed growth across most regions, driven by increased use in chronic ITP and as first-line and/or second-line treatment for severe aplastic anemiaScemblix(USD 52 million, nm cc) continued its strong launch uptake demonstrating the high unmet need in CML, particularly patients previously treated with 2 or more tyrosine kinase inhibitors, or with the T315I mutationLeqvio(USD 42 million, nm cc) launch is ongoing, with focus on patient on-boarding, removing access hurdles and enhancing medical educationIlaris(USD 301 million, +14% cc) showed continued growth across all geographiesTafinlar + Mekinist(USD 465 million, +8% cc) sales grew across all geographies, driven by demand in BRAF+ adjuvant melanoma and NSCLC indicationsJakavi(USD 388 million, +8% cc) sales grew (cc) mainly in Europe, Emerging Growth Markets and Japan, driven by strong demand in both the myelofibrosis and polycythemia vera indicationsPiqray(USD 112 million, +30% cc) sales grew mainly in the US, benefiting from indication expansion into PIK3CA-related overgrowth spectrum (PROS)Mayzent(USD 99 million, +28% cc) continued to grow in patients with multiple sclerosis showing signs of progression despite being on other treatmentsLutathera(USD 128 million, +15% cc) sales grew across all geographies, with approximately 500 centers actively treating patients globallyCosentyx(USD 1,080 million, -9% cc), with ex-US growing +5% (cc). US sales growth was impacted by a revenue deduction true-up for Cosentyx (mainly due to higher than expected Medicaid patient mix), which was related to prior quarters in 2022. For the full year, Cosentyx grew +5% (cc) worldwideSandoz Biopharmaceuticals(USD 517 million, +3% cc) with growth in Europe, Canada and Latin AmericaEmerging Growth Markets*Grew +5% (cc) overall. China declined (-2% cc) to USD 581 million, with sales impacted by COVID-19 related regional lockdowns. For the full year, China grew +6% (cc) *All markets except the US, Canada, Western Europe, Japan, Australia, and New Zealand nm= not meaningful Net sales of the top 20 Innovative Medicines products in 2022 Q4 2022% changeFY 2022% change USD mUSDccUSD mUSD ccCosentyx / excl. revenue deduction true-up*1 080-13 / -6*-9 / -2*4 78815Entresto1 29136444 6443137Promacta/Revolade 5404112 08849Gilenya 346-47-442 013-28-24Tasigna 475-601 923-7-1Lucentis 398-22-121 874-13-4Tafinlar + Mekinist 465281 770511Jakavi 388-581 561-29Zolgensma 309-10-51 37015Xolair 323-13-31 365-46Sandostatin 305-12-81 238-12-10Kisqali 35725331 2313138Ilaris 3016141 133715Kesimpta 3691511571 092194200Galvus Group 209-25-16 859-21-12Gleevec/Glivec 175-25-18 745-27-22Exforge Group 159-19-12 743-18-12Diovan Group 142-25-16 652-16-9Kymriah 139-35 536-9-2Afinitor/Votubia 106-39-32 512-45-41Top 20 products total7 877-4232 137-15 * Sales growth with/without true-up: US Cosentyx sales growth was impacted by a revenue deduction true-up (mainly due to higher than expected Medicaid patient mix), which was related to prior quarters in 2022 R&D update - key developments from the fourth quarter New approvals PluvictoEC approval for treatment of patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen-receptor pathway inhibition and taxane-based chemotherapy Results from ongoing trials and other highlights PluvictoPh3 PSMAfore trial met its primary endpoint, demonstrating statistically significant and clinically meaningful improvement in radiographic PFS in patients with PSMA-positive mCRPC who have been treated with androgen-receptor pathway inhibition. No unexpected safety findings were observed. Detailed data to be presented at an upcoming medical meeting with submission to regulatory authorities for approval planned for 2023IptacopanPh3 APPLY-PNH study met both primary and most secondary endpoints demonstrating iptacopan’s superiority over anti-C5 treatment in adult PNH patients with residual anemia despite prior anti-C5 treatment. Iptacopan demonstrated an 80% difference to anti-C5 in the estimated proportion of patients achieving ≥2 g/dL Hb-level increases from baseline and a 67% difference to anti-C5 in the estimated proportion of patients achieving ≥12 g/dL Hb levels without the need for red blood cell transfusions. Iptacopan also provided blood-transfusion independence for almost all patients with no serious cases of breakthrough hemolysis and clinically meaningful patient-reported fatigue improvements. Data presented at ASH 2022 Ph3 APPOINT-PNH study (evaluating iptacopan in complement-inhibitor-naïve PNH patients) met its primary endpoint. With iptacopan, a significant proportion of patients achieved clinically meaningful Hb-level increases of ≥2 g/dL from baseline without the need for blood transfusions at 24 weeks. Detailed data to be presented at an upcoming medical meeting and included in iptacopan PNH global regulatory submissions planned in 2023KisqaliPh2 RIGHT Choice trial demonstrated approximately one year PFS benefit of Kisqali plus ET over combination chemotherapy (24 months compared to 12.3 months; HR=0.54; p=.0007) in the 1L setting for pre- and perimenopausal patients with aggressive forms of HR+/HER2− mBC, including patients with visceral crisis. RIGHT Choice is the first randomized study comparing a CDK4/6i plus ET vs. combination CT in aggressive HR+/HER2− mBC. Data presented at SABCS 2022LeqvioNew long-term data from the ORION-3 open-label study demonstrated effective and sustained reductions in LDL cholesterol over four years of treatment. At any time throughout the trial, approximately 80% of patients reached an LDL-C level of <70mg/dL. Data presented at AHA 2022Ganaplacide/ lumefantrine-SDF combinationNovartis and Medicines for Malaria Venture announced that ganaplacide/ lumefantrine would advance to a Ph3 study in patients with acute uncomplicated malaria due to Plasmodium falciparumBranaplamNovartis ended the development of branaplam in Huntington’s Disease based on an overall assessment of potential benefit-risk from the Ph2b VIBRANT-HD study Capital structure and net debt Retaining a good balance between investment in the business, a strong capital structure and attractive shareholder returns remains a priority. In 2022, Novartis repurchased a total of 126.2 million shares for USD 10.8 billion on the SIX Swiss Exchange second trading line, including 115.3 million shares (USD 9.9 billion) under the up-to USD 15 billion share buyback announced in December 2021 and 10.9 million shares (USD 0.9 billion) to mitigate dilution related to participation plans of associates. In addition, 1.4 million shares (USD 0.1 billion) were repurchased from associates. In the same period, 12.3 million shares (for an equity value of USD 0.9 billion) were delivered as a result of option exercises and share deliveries related to participation plans of associates. Consequently, the total number of shares outstanding decreased by 115.3 million versus December 31, 2021. These treasury share transactions resulted in a decrease in equity of USD 10.0 billion and a net cash outflow of USD 10.6 billion. As of December 31, 2022, the net debt increased to USD 7.2 billion compared to USD 0.9 billion at December 31, 2021. The increase was mainly due to the USD 7.5 billion annual dividend payment and the net cash outflow for treasury share transactions of USD 10.6 billion, partially offset by USD 11.9 billion free cash flow during 2022. As of Q4 2022, the long-term credit rating for the company is A1 with Moody’s Investors Service and AA- with S&P Global Ratings. 2023 outlook Barring unforeseen events; growth vs prior year in cc Innovative MedicinesSales expected to grow low-to-mid single digitCore OpInc expected to grow mid-to-high single digitNovartis ex. Sandoz(IM + Corporate)Sales expected to grow low-to-mid single digitCore OpInc expected to grow mid-to-high single digitNovartis incl. Sandoz (IM + Sandoz + Corporate)*Sales expected to grow low-to-mid single digitCore OpInc expected to grow mid single digit * Novartis Group guidance, assuming Sandoz would remain within the Group for the entire FY 2023 Barring unforeseen events; growth vs prior year in cc SandozSales expected to grow low-to-mid single digitCore OpInc expected to decline low double digit, reflecting required stand-up investments to transition Sandoz to a separate company and continued inflationary pressures Our guidance assumes that we see a continuing return to normal global healthcare systems, including prescription dynamics, and that no Sandostatin LAR generics enter in the US in 2023. We continue to expect that the planned Sandoz spin-off is completed in H2 2023.Foreign exchange impactIf late-January exchange rates prevail for the remainder of 2023, the foreign exchange impact for the year would be zero to positive 1 percentage points on net sales and negative 1 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website. Annual General Meeting Dividend proposalThe Novartis Board of Directors proposes a dividend payment of CHF 3.20 per share for 2022, up 3.2% from CHF 3.10 per share in the prior year, representing the 26th consecutive dividend increase since the creation of Novartis in December 1996. Shareholders will vote on this proposal at the Annual General Meeting on March 7, 2023. Reduction of share CapitalThe Novartis Board of Directors proposes to cancel 126 243 500 shares (repurchased under the authorizations of March 2, 2021 and March 4, 2022) and to reduce the share capital accordingly by CHF 63.1 million, from CHF 1 201 860 626 to CHF 1 138 738 876. Potential further share repurchasesAs of December 31, 2022, the remaining available amount under the existing shareholder authorities granted at the 2021 and 2022 annual general meetings is CHF 8.3 billion. To allow for the full execution of the already announced share buyback of up to USD 15 billion and potential additional share buybacks, the Board of Directors proposes that shareholders, in addition to the remaining authorization of CHF 8.3 billion, authorize the Board of Directors to repurchase shares as deemed appropriate from time to time up to a maximum of CHF 10 billion between the 2023 Annual General Meeting and the 2026 Annual General Meeting. Nomination for election to the Board of DirectorsThe Novartis Board of Directors announced today that it is nominating John D. Young for election to the Board. He retired from Pfizer in June 2022 where he held several senior positions over more than 30 years and served as a member of Pfizer’s Executive Leadership Team since 2012. John successfully led and developed multi-ten-billion dollar global businesses and brings a wealth of industry experience in leadership, strategy, business development and commercialization of innovative medicines to the Board of Directors. John D. Young currently serves on the Boards of Johnson Controls International, Haleon PLC, Arvinas Inc, and privately held biotech, Imbria Pharmaceuticals. Re-elections of the Board Chair and the members of the Board of Directors The Novartis Board of Directors proposes the re-election of Joerg Reinhardt (also as Board Chair), Nancy C. Andrews, Ton Buechner, Patrice Bula, Elizabeth Doherty, Bridgette Heller, Frans van Houten, Daniel Hochstrasser, Simon Moroney, Ana de Pro Gonzalo, Charles L. Sawyers, and William T. Winters as members of the Board of Directors. Andreas von Planta has already announced that he will not stand for re-election. The Board of Directors and the Executive Committee of Novartis thank him for many years of distinguished services on the Board and his outstanding contributions to the company. Re-elections and elections to the Compensation Committee The Novartis Board of Directors proposes the re-election of Patrice Bula, Bridgette Heller, Simon Moroney, and William T. Winters as members of the Compensation Committee. The Board of Directors intends to designate Simon Moroney again as Chairman of the Compensation Committee. Key figures1 Excluding Roche income ReportedGroupQ4 2022Q4 2021% changeQ4 2021% change USD m USD mUSDcc USD mUSDccNet sales12 69013 229-43 13 229-43Operating income1 9492 562-24-14 2 562-24-14As a % of sales15.419.4 19.4 Core operating income4 0303 819615 3 819615As a % of sales31.828.9 28.9 Net income1 4661 671-122 16 306-91-90EPS (USD)0.690.75-87 7.29-91-89Core net income3 2513 044717 3 135414Core EPS (USD)1.521.361223 1.40919Cash flows from operating activities4 1113 8846 3 8846 Free cash flow 3 5523 02717 3 02717 Innovative MedicinesQ4 2022Q4 2021% change USD m USD mUSDcc Net sales10 36010 704-33 Operating income1 9452 468-21-12 As a % of sales18.823.1 Core operating income3 7683 596514 As a % of sales36.433.6 SandozQ4 2022Q4 2021% change USD m USD mUSDcc Net sales2 3302 525-80 Operating income273386-29-20 As a % of sales11.715.3 Core operating income391528-26-18 As a % of sales16.820.9 CorporateQ4 2022Q4 2021% change USD m USD mUSDcc Operating loss-269-29282 Core operating loss-129-3055857 Excluding Roche income ReportedGroupFY 2022FY 2021% change FY 2021% change USD m USD mUSDcc USD mUSDccNet sales50 54551 626-24 51 626-24Operating income9 19711 689-21-13 11 689-21-13As a % of sales18.222.6 22.6 Core operating income16 66516 58808 16 58808As a % of sales33.032.1 32.1 Net income6 9558 661-20-9 24 018-71-67EPS (USD)3.193.86-17-7 10.71-70-66Core net income13 35213 099211 14 094-53Core EPS (USD)6.125.84514 6.29-36Cash flows from operating activities14 23614 549-2 15 071-6 Free cash flow 11 94512 760-6 13 282-10 Innovative MedicinesFY 2022FY 2021% change USD m USD mUSDcc Net sales41 29641 995-24 Operating income8 78610 688-18-9 As a % of sales21.325.5 Core operating income15 23715 21508 As a % of sales36.936.2 SandozFY 2022FY 2021% change USD m USD mUSDcc Net sales9 2499 631-44 Operating income1 4481 600-10-2 As a % of sales15.716.6 Core operating income1 9032 064-8-1 As a % of sales20.621.4 CorporateFY 2022FY 2021% change USD m USD mUSDcc Operating loss-1 037-599-73-84 Core operating loss-475-6913128 1Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 50 of the Condensed Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.Detailed financial results accompanying this press release are included in the Condensed Financial Report at the link below:https://ml-eu.globenewswire.com/resource/download/0651bdfc-55fc-4463-8b19-a498f6d67337/ Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995, that can generally be identified by words such as “continued,” “growth,” “ongoing,” “to grow,” “on track,” “to become, “to leverage,” “growing,” “building,” “launch,” “looking ahead,” “expect,” “continue,” “to deliver,” “transformation,” “focus,” “address,” “growing,” “accelerate,” “continuing,” “remains,” “scaling,” “on track,” “expected,” “guidance,” “to be presented,” “outlook,” “driven,” “long-term,” “driven,” “innovation,” “transformative,” “priority,” “potential,” “can,” “submissions,” “will,” “proposes,” “proposal,” “to reduce,” “advance,” or similar expressions, or by express or implied discussions regarding potential new products, potential new indications for existing products, potential product launches, or regarding potential future revenues from any such products; or regarding potential future, pending or announced transactions; regarding potential future sales or earnings of the Group or any of its divisions; or by discussions of strategy, plans, expectations or intentions; or regarding the Group’s liquidity or cash flow positions and its ability to meet its ongoing financial obligations and operational needs; or regarding the conclusion of the strategic review of Sandoz, our planned 100% spin-off of Sandoz, through which we plan to become a fully focused Innovative Medicines business. Such forward-looking statements are based on the current beliefs and expectations of management 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. You should not place undue reliance on these statements. In particular, our expectations could be affected by, among other things: liquidity or cash flow disruptions affecting our ability to meet our ongoing financial obligations and to support our ongoing business activities; the impact of a partial or complete failure of the return to normal global healthcare systems including prescription dynamics; global trends toward healthcare cost containment, including ongoing government, payer and general public pricing and reimbursement pressures and requirements for increased pricing transparency; uncertainties regarding potential significant breaches of data security or data privacy, or disruptions of our information technology systems; regulatory actions or delays or government regulation generally, including potential regulatory actions or delays with respect to the development of the products described in this press release; the potential that the benefits and opportunities expected from our planned 100% spin-off of Sandoz may not be realized or may be more difficult or take longer to realize than expected; the uncertainties in the research and development of new healthcare products, including clinical trial results and additional analysis of existing clinical data; our ability to obtain or maintain proprietary intellectual property protection, including the ultimate extent of the impact on Novartis of the loss of patent protection and exclusivity on key products; safety, quality, data integrity, or manufacturing issues; uncertainties involved in the development or adoption of potentially transformational technologies and business models; uncertainties regarding actual or potential legal proceedings, investigations or disputes; our performance on environmental, social and governance measures; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; uncertainties regarding future global exchange rates; uncertainties regarding future demand for our products; 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 as a result of new information, future events or otherwise. All product names appearing in italics are trademarks owned by or licensed to Novartis Group companies. About Novartis Novartis is reimagining medicine to improve and extend people’s lives. We deliver high-value medicines that alleviate society’s greatest disease burdens through technology leadership in R&D and novel access approaches. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. About 106,000 people of more than 140 nationalities work together to bring Novartis products to nearly 800 million people around the world. Find out more at https://www.novartis.com. Novartis will conduct a conference call with investors to discuss this news release today at 14:00 Central European time and 8:00 Eastern Time. A simultaneous webcast of the call for investors and other interested parties may be accessed by visiting the Novartis website. A replay will be available after the live webcast by visiting https://www.novartis.com/investors/event-calendar. Detailed financial results accompanying this press release are included in the condensed financial report at the link below. Additional information is provided on Novartis divisions and pipeline of selected compounds in late stage development and a copy of today's earnings call presentation can be found at https://www.novartis.com/investors/event-calendar. Novartis issued its 2022 Annual Report today, and it is available at www.novartis.com. Novartis will also file its 2022 Annual Report on Form 20-F with the US Securities and Exchange Commission today, and will post this document on www.novartis.com. Novartis shareholders may receive a hard copy of either of these documents, each of which contains our complete audited financial statements, free of charge, upon request. Novartis also issued its Novartis in Society Integrated Report 2022 today, and it is available at www.novartis.com. Important dates March 7, 2023Annual General MeetingApril 25, 2023First quarter 2023 resultsJuly 18, 2023Second quarter & Half year 2023 resultsOctober 24, 2023Third quarter & Nine months 2023 results Please find full media release in English attached and on the following link: Media release (PDF) Further language versions are available through the following links: German version is available through the following link:Medienmitteilung (PDF) French version is available through the following link:Communiqué aux médias (PDF)

Drug ApprovalFinancial StatementBiosimilarAcquisition

100 Deals associated with Siponimod Fumaric Acid

External Link

KEGG	Wiki	ATC	Drug Bank
-	Siponimod Fumaric Acid	L04AA42	DB12371

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Multiple Sclerosis, Secondary Progressive	LI	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis, Secondary Progressive	EU	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis, Secondary Progressive	IS	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis, Secondary Progressive	NO	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis	US	Novartis Pharmaceuticals Corp.	26 Mar 2019

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis, Secondary Progressive	Phase 3	RU	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	JP	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	US	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	AR	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	TR	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	CN	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	CH	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	IL	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	AU	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple sclerosis relapse	Preclinical	US	Novartis Pharmaceuticals Corp.	14 Feb 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04792567 (AMA-VACC, CTgov)	Phase 4	Multiple Sclerosis, Secondary Progressive	41	BAF312+BNT162+mRNA-1273 (Siponimod - Continuous)	rbljizyatb(vgtjwobkgq) = xrhgssiemd vrkpaltcat (mloahnumvw, feipxkaiyc - zxlxgkitrv) View more	-	17 May 2024
				BAF312+BNT162+mRNA-1273 (Siponimod- Interrupted)	rbljizyatb(vgtjwobkgq) = ellqpdgwds vrkpaltcat (mloahnumvw, delmfmzugc - mshlvcssql) View more
ECTRIMS2023	Not Applicable	Multiple Sclerosis	67	Siponimod	gumtihciie(hgvsfvairq) = neorfkrodt zfqofgvbbo (hxwgnowqdx )	-	01 Oct 2023
EAN	Not Applicable	-	-	Siponimod	afgnstipaj(squdmbosfo) = svqxjkzcwx fgqylxeuwx (frxephxhpr )	-	28 Jun 2023
ACTRIMS2023	Not Applicable	Multiple Sclerosis, Secondary Progressive Second line	29	Siponimod	(zqisngchzl) = 4 patients discontinued treatment due to adverse events and one by personal decision. 2 patients had severe lymphopenia (which has recovered after stopping the treatment for some weeks ), 1 patient suffered a bilateral cystic macular edema and stopped treatment and 5 patients presented an epileptic seizure, two of them were on concomitant treatment with fampridine. Three of them have discontinued the treatment. No alterations in liver enzymes have been observed. No documented increase in frequent infections. llgkrwoagu (zbnrhlmpiw ) View more	Positive	30 May 2023
ECTRIMS2022	Not Applicable	COVID-19	-	Fingolimod	txkspjjlqs(emrhvwbrkc) = ghoxsnjdaa bhnvozlahd (xcqahjmnuw ) View more	-	12 Oct 2022
				Siponimod	txkspjjlqs(emrhvwbrkc) = kvizpglozf bhnvozlahd (xcqahjmnuw ) View more
ECTRIMS2022	Not Applicable	Multiple Sclerosis, Secondary Progressive CYP2C9 genotype	-	Siponimod 2mg	myglytloyr(tbymfvyagn) = A total of 90 patients discontinued the study; 48 prior to and 42 after siponimod exposure hdytkommoi (kmpmyvxwwo )	-	12 Oct 2022
				Siponimod 1mg
EAN	Not Applicable	-	-	Siponimod	bfuqcktdhy(plmqcqzeah) = czpjubselh rgcpltyaot (baukxabzgn )	-	24 Jun 2022
				Placebo	bfuqcktdhy(plmqcqzeah) = hodshrqbvf rgcpltyaot (baukxabzgn )
NCT01665144 (EXPAND, Pubmed)	Phase 3	Multiple Sclerosis, Secondary Progressive	779	Siponimod	wtzawllgci(fyjxigixai) = thsampexxg hcgstgviku (hfxvzoosce )	Positive	31 May 2022
				Placebo	wtzawllgci(fyjxigixai) = imkoohjeoj hcgstgviku (hfxvzoosce )
ACTRIMS2022	Not Applicable	Multiple Sclerosis antiCD20 therapies \| ocrelizumab \| fingolimod	-	OCR	(cqubjhooty) = pybrrhltqq zkwlcegbus (rczzhmbgan, 0.06 - 0.34) View more	Positive	16 May 2022
				Ofatumumab	(cqubjhooty) = bvnhyddzdq zkwlcegbus (rczzhmbgan, 0.03 - 0.14) View more
P9-4.008 (AAN2022)	Not Applicable	Multiple Sclerosis	1,985	Diroximel Fumarate (DRF)	zffkotudhq(bdnoqedxzl) = ksxeuovcoc ecbosrtnjx (nbohbwnrde )	Positive	03 May 2022
				Dimethyl Fumarate (DMF)	zffkotudhq(bdnoqedxzl) = quaidzklbw ecbosrtnjx (nbohbwnrde )

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