Delving into the Latest Updates on Siponimod Fumaric Acid with Synapse

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 Date26 Aug 2025

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.

CTIS2024-512283-65-00

/ RecruitingPhase 4IIT

Exploring the effect of a novel therapy on chronic intrathecal inflammation in patients with active progressive multiple sclerosis

Start Date29 May 2023

Sponsor / Collaborator

Azienda Ospedaliera Universitaria Integrata Verona

100 Clinical Results associated with Siponimod Fumaric Acid

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100 Translational Medicine associated with Siponimod Fumaric Acid

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100 Patents (Medical) associated with Siponimod Fumaric Acid

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340

Literatures (Medical) associated with Siponimod Fumaric Acid

01 Feb 2026·Therapeutic Advances in Neurological Disorders

Positioning siponimod and the post-treatment gap: the unmet needs of SPMS patients in Italian real-world practice

Article

Author: D’Amico, Emanuele ; Foschi, Matteo ; Mirabella, Massimiliano ; Cicia, Alessandra ; Cellerino, Maria ; Borriello, Giovanna ; Inglese, Matilde ; Romano, Giuseppe ; Avolio, Carlo ; Baldisseri, Francesco ; Bianco, Assunta ; Zanghì, Aurora ; Di Filippo, Paola Sofia ; Signoriello, Elisabetta ; Lus, Giacomo

Background::

Siponimod, a selective sphingosine-1-phosphate receptor modulator was approved for patients with Secondary progressive Multiple Sclerosis (SPMS) with ongoing disease activity. However, its real-world positioning and management after discontinuation remain challenging.

Objectives::

To evaluate the real-world use of siponimod in Italian real world setting, focusing on discontinuation rates, possible predictors, and post-treatment management.

Methods::

A retrospective, multicenter study on patients treated with siponimod across six Italian MS centers. Demographics, prior disease modifying therapy (DMTs), reasons for discontinuation, adverse events, and subsequent therapies were collected. Statistical analyses included propensity-adjusted Cox model.

Results::

A total cohort of 188 patients (63.8% female, median age 52 years) was enrolled, out of them 76(40.4%) discontinued siponimod, with a median treatment duration of 26 months. The main reason for discontinuation was safety concerns (72.4%), particularly persistent lymphopenia (43.6%) and recurrent infections (27.3%). Disease activity accounted for 27.6% of discontinuations. No significant demographic or clinical predictors of discontinuation were identified. After discontinuation, 49 patients (64%) started a new DMT, most commonly ocrelizumab ( n = 22) or cladribine ( n = 15), while 25 (32.9%) received no further therapy.

Conclusion::

High discontinuation rates, mainly due to safety, and frequent post-treatment gaps highlight the need for improved, individualized management strategies for SPMS after siponimod.

01 Jan 2026·BRAIN RESEARCH BULLETIN

Cerebellar subregional atrophy in relapsing-remitting multiple sclerosis: Stage-dependent dynamics and pharmacological modulation

Article

Author: Li, Yongmei ; Yu, Bin ; Feng, Jinzhou ; Zhang, Xiaohui ; Zhang, Zhiwei ; Zhang, Kai ; Chen, Xiaoya ; Du, Silin

BACKGROUND:

Cerebellar atrophy is increasingly recognized as an important pathological feature of multiple sclerosis (MS). However, the specific patterns at different stages and their alteration by disease-modifying therapies (DMTs) are not well comprehended.

OBJECTIVE:

This study aimed to investigate stage-dependent cerebellar subregional volume changes in relapsing-remitting MS (RRMS) and evaluate the effects of different DMT classes on cerebellar atrophy and clinical outcomes.

METHODS:

A total of 181 patients with RRMS and 99 healthy controls were recruited for this study. Patients were stratified by lesion activity into acute-active, chronic-active, and chronic-inactive subgroups, and by pharmacological mechanism into untreated, sphingosine-1-phosphate (S1P)_T (siponimod, fingolimod, and ozanimod) and not_S1P_DMT (dimethyl fumarate and teriflunomide). Cerebellar subregional volumes were quantified using the deep learning-based tool, CerebNet. Group comparisons were conducted, and interaction effects were examined. The correlations between the cerebellar subregions and cognition were subsequently analyzed.

RESULTS:

In the lesion-activity subgroups, significant volume loss was detected in several posterior cerebellar lobules, including Crus II, VIIIa/b, VIIb, X, Crus I, and IX (all p < 0.05). The acute-active subgroup exhibited additional atrophy in anterior lobules I-IV and vermis IX compared with the chronic-active subgroup (all p < 0.05). In the treatment subgroups, widespread reductions were observed in the posterior lobules Crus I/II, V, VIIb, VIIIb, IX, and X, with most decreases appearing in the untreated groups (all p < 0.05). Pairwise comparisons displayed region-specific patterns: left VIIIa volume was reduced in the MS_noDrug and MS_not_S1P_DMT groups but increased in the S1P_DMT group, whereas right lobule V in the S1P_DMT and vermis VI in the MS_not_S1P_DMT were both higher (all p < 0.05). The interaction effects of disease stage and treatment were mainly localized to lobules IX and VIIIb, and the volumes of bilateral IX lobules showed a weak positive correlated with cognitive performance.

CONCLUSION:

This study demonstrated stage-specific patterns of cerebellar atrophy in RRMS and the heterogeneous, stage-dependent effects of DMTs on posterior cerebellar subregions. Lobules IX and VIIIb emerged as critical loci linking pharmacological modulation with cognitive outcomes. These findings suggest that these regions may serve as potential imaging biomarkers of therapeutic response and prognosis in MS.

01 Jan 2026·MOLECULAR NEUROBIOLOGY

Dual Mechanisms of Cognitive Function and Pathological Improvements by the Selective S1PR1/5 Modulator Siponimod in 3xTg-AD Mice

Article

Author: Ding, Yaqi ; Lei, Xiaoyang ; Yang, Sushuang ; He, Dian ; Tang, Chao ; Xu, Bingyang ; Zhang, Ming

Alzheimer's disease (AD) is characterized by progressive cognitive decline, with neuroinflammation and myelin dysfunction as crucial pathological mechanisms. Siponimod, a selective S1PR1/5 modulator, shows promising therapeutic potential through enhanced brain penetration and improved pharmacokinetic properties compared to first-generation modulators. Network pharmacology and molecular docking analyses were utilized to comprehensively elucidate the underlying mechanisms of Siponimod in the context of AD. Specifically, network pharmacology identified key targets and pathways associated with Siponimod, while molecular docking facilitated predictions of binding affinities to these targets. For in vitro assessments, BV2 microglia cells were used to investigate the effects of Siponimod after stimulation with LPS, focusing on inflammatory responses and cellular signaling pathways. Concurrently, in vivo studies employed the 3xTg-AD mouse model to investigate behavioral outcomes related to cognitive function, alongside evaluations of neuroinflammation and the integrity of myelin sheaths. Siponimod treatment resulted in a significant reduction in pro-inflammatory cytokines and ROS production in BV2 microglia cells, thereby indicating its robust anti-inflammatory and antioxidant properties. In the 3xTg-AD mouse model, administration of Siponimod led to marked improvements in cognitive performance as assessed through various behavioral tests. Additionally, there was a noteworthy decrease in Aβ plaque deposition, coupled with evidence of myelin repair, which was reflected in the increased expression of myelination-related proteins, namely OLIG2 and MBP. Furthermore, Siponimod was found to activate the PI3K-AKT signaling pathway, which plays a crucial role in promoting neuroprotection and enhancing cellular resilience against neurodegenerative processes. This study demonstrates that Siponimod effectively treats AD through dual mechanisms: reducing neuroinflammation and promoting myelin repair via the S1PR1/5 and PI3K-AKT signaling pathway. These findings suggest Siponimod's potential as a promising therapeutic agent for AD treatment.

36

News (Medical) associated with Siponimod Fumaric Acid

02 Feb 2026

·www.biospace.com

Teva Canada Announces Strategic Partnership with Novartis Canada to Relaunch Mayzent® for Multiple Sclerosis Patients in Canada

TORONTO , Feb. 2, 2026 /CNW/ - Teva Canada Limited (Teva Canada) is announcing a new commercialization and supply agreement with Novartis Pharmaceuticals Canada Inc. (Novartis Canada) for Mayzent® (siponimod), an innovative oral treatment for secondary progressive multiple sclerosis (SPMS) with active disease. Under the partnership, Teva Canada will assume exclusive responsibility for the promotion, distribution, and commercialization of Mayzent® in Canada. This collaboration leverages Teva's established central nervous system (CNS) expertise and national commercial infrastructure, ensuring continued access to Mayzent® for Canadian patients and healthcare professionals. The agreement is designed to maximize the reach and impact of Mayzent®, building on Teva's established history with neurologists and MS specialists across the country. "This is about more than a product - it's about people," said Fabien Paquette, General Manager, Teva Canada. "Through this partnership, we are reaffirming our dedication to the MS community and to patient-centred care. Teva Canada is proud to lead with purpose, ensuring access and support for those who need it most. We are all in for better health." "This agreement reflects our shared responsibility to support people living with MS," said Dimitri Gitas, Country President, Novartis Canada "Through this partnership, we're strengthening support for Canadians living with multiple sclerosis and advancing better health outcomes nationwide." Mayzent® is indicated in Canada for the treatment of patients with secondary progressive multiple sclerosis (SPMS) with active disease, as evidenced by relapses or imaging features characteristic of multiple sclerosis inflammatory activity, to delay the progression of physical disability. About Teva Canada Teva Canada, a subsidiary of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), is proud to celebrate 60 years of serving the health of Canadians. As one of the world's largest suppliers of generic, biosimilar, and innovative medicines, we are all in for better health - committed to delivering reliable, high-quality treatments. With facilities in Markham, Stouffville, Toronto, and Montréal, we employ over 850 people and manufacture 70% of the medicines we sell in Canada locally, reinforcing our commitment to accessibility and supporting the Canadian economy. Learn more at . Forward-Looking Statements This news release contains forward-looking statements regarding the commercialization of Mayzent® in Canada. Actual results may differ materially due to various risks and uncertainties. SOURCE Teva Canada

06 Jan 2026

·pmlive.com

Novartis agrees to lower drug prices in deal with US government

Novartis has announced an agreement with the US government to lower the prices of its medicines in the US and support continued investment in US R&D and manufacturing. Novartis has agreed to take a variety of actions with the goal of meeting the US government’s current drug pricing priorities. These include: Launching future medicines with comparable prices across high-income countries Building direct-to-patient platforms for Mayzent (siponimod), Rydapt (midostaurin) and Tabrecta (capmatinib) Applying to participate in the GENEROUS (GENErating cost Reductions fOr US Medicaid) programme, designed to further improve access to Medicaid medicines Supporting efforts to address global imbalances in pharmaceutical innovation investment. In 2025, Novartis announced a commitment to invest $23bn to expand its manufacturing and R&D presence in the US over the next five years. Since the announcement in April 2025, Novartis has taken a number of key steps towards this goal. It announced a new $1.1bn biomedical research hub in San Diego, California, as well as a new flagship manufacturing hub in North Carolina. This hub will include three new facilities and enable end-to-end manufacturing capabilities. Additionally, Novartis opened a new radioligand therapy (RLT) manufacturing facility in Carlsbad, California, and advanced plans to build new RLT manufacturing facilities in Florida and Texas. The agreement means that US pharmaceutical tariffs on the company will be delayed for three years. Vas Narasimhan, CEO of Novartis, said: “This agreement continues our long-term partnership with the US government to advance the development and manufacturing of breakthrough treatments for patients in the US. “We are committed to working with governments worldwide to ensure innovation is appropriately valued and that our medicines reach the patients who need them most.”

29 Dec 2025

·www.mobihealthnews.com

TrumpRx signs agreement with nine new pharma manufacturers

The White House announced it has signed nine new agreements with pharmaceutical companies Amgen , Bristol Myers Squibb , Boehringer Ingelheim , Genentech , Gilead Sciences , GSK , Merck , Novartis and Sanofi to offer medications through TrumpRx at discounted rates. According to the White House, Boehringer Ingelheim's Jentadeuto for type 2 diabetes will be listed for $55 for U.S. patients, Bristol Myers Squibb's Reyataz for HIV will be $217, Genentech's Xofluza flu medication will be $50, and Amgen's Repatha, used to lower high cholesterol, will be offered through TrumpRx for $239. TrumpRx will also offer Gilead Sciences' Epclusa hepatitis C medication for $2,425, Merck's Januvia for diabetes at $100 and Novartis' Mayzent for multiple sclerosis for $1,137, and Sanofi will reduce the price of its prescription blood thinner, Plavix, to $16. Sanofi will also list its insulin products on TrumpRx at $35 per month’s supply, and GSK will reduce the prices of its inhaler portfolio, including its asthma inhaler Advair Diskus 500/50, to $89. The pharma giants are also collectively investing at least $150 billion in U.S. manufacturing and donating active pharmaceutical ingredients to the Strategic Active Pharmaceutical Ingredients Reserve, which aims to increase the U.S. supply of such products in the event of an emergency and reduce America's reliance on foreign nations. THE LARGER TREND Earlier this month, Boehringer Ingelheim announced it had signed an agreement with the Trump administration that allows the pharma giant to be excluded from potential Section 232 tariffs. The pharma giant plans to spend $10 billion to expand its research and development and manufacturing operations in the U.S. through 2028, including $1 billion for capital expenditures. The agreement means the bulk of Boehringer's medications for U.S. patients will be produced in the United States. In November, the White House announced it signed agreements with Eli Lilly and Company and Novo Nordisk to offer GLP-1s Zepbound, orforglipron, Ozempic and Wegovy through TrumpRx at a discounted rate. TrumpRx launched in September and announced it brokered a deal with Pfizer to offer some of the pharma giant's medications at a discount through the prescription digital marketplace. That deal also allowed Pfizer to avoid U.S. tariffs on overseas-made drugs for three years by offering its medications through TrumpRx.

Drug Approval

100 Deals associated with Siponimod Fumaric Acid

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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	European Union	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis, Secondary Progressive	Iceland	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis, Secondary Progressive	Liechtenstein	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis, Secondary Progressive	Norway	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis	United States	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 relapse	Phase 3	United States	Novartis Pharmaceuticals Corp.	14 Feb 2019
Rhabdomyosarcoma	Phase 3	United States	Novartis Pharmaceuticals Corp.	14 Feb 2019
Alzheimer Disease	Phase 2	United States	Novartis AG	26 Aug 2025
Alzheimer Disease	Phase 2	United States	Laboratory Corporation of America Holdings	26 Aug 2025
Mild cognitive disorder	Phase 2	United States	Novartis AG	26 Aug 2025
Mild cognitive disorder	Phase 2	United States	Laboratory Corporation of America Holdings	26 Aug 2025
Cerebral Hemorrhage	Phase 2	United States	Novartis Pharmaceuticals Corp.	24 Dec 2017
Hemorrhagic stroke	Phase 2	United States	Novartis Pharmaceuticals Corp.	24 Dec 2017
Polymyositis	Phase 2	United States	Novartis Pharmaceuticals Canada, Inc.	24 Apr 2013
Polymyositis	Phase 2	Canada	Novartis Pharmaceuticals Canada, Inc.	24 Apr 2013

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04925557 (CTgov)	Phase 2/3	Multiple Sclerosis, Secondary Progressive	8	Ocrevus (Ocrevus)	acmekycbdt(zreykybmrb) = eqwgwajvan ocbdewzfhu (eegcnmomkf, zxhdtoqxti - owzjfjeawe) View more	-	13 May 2025
				Mayzent (Mayzent)	acmekycbdt(zreykybmrb) = nbxiloeqaa ocbdewzfhu (eegcnmomkf, voemrzsxop - lrzfklkzka) View more
NCT03623243 (EXCHANGE, Pubmed \| Mult Scler)	Phase 3	Multiple sclerosis relapse	185	Siponimod	sbbvmdbvps(wmodqtefre) = 3.8% (n = 7) gwephbwyrq (hiahdkjhso ) View more	Positive	01 May 2025
NCT04792567 (AMA-VACC, CTgov)	Phase 4	Multiple Sclerosis, Secondary Progressive	41	BAF312+BNT162+mRNA-1273 (Siponimod - Continuous)	pzgiscnzdo = oefdahjwvw vkfwhjmckr (imvvdybzgc, wcwxoxhnms - zuijzljioo) View more	-	17 May 2024
				BAF312+BNT162+mRNA-1273 (Siponimod- Interrupted)	pzgiscnzdo = nxtklbuvgp vkfwhjmckr (imvvdybzgc, warzvtdzno - qwooseboyd) View more
ECTRIMS2023	Not Applicable	Multiple Sclerosis	67	Siponimod	ugittbvvht(yoeqombqbx) = wlxhkczhjf slnxfbftpz (gcakbrbaqp )	-	01 Oct 2023
NCT03623243 (EXCHANGE, CTgov)	Phase 3	Rhabdomyosarcoma \| Multiple sclerosis relapse	185	Siponimod	gbmkvdmxsa = kpjpodwhla nwatxdmyxu (ubjtampxkz, vjzkacfyss - cjncuuookn) View more	-	20 Jul 2023
ACTRIMS2023	Not Applicable	Multiple Sclerosis, Secondary Progressive Second line	29	Siponimod	mhwyowuryk(xiqorcpsfi) = 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. mntfxfxkjc (ahumtbrmeo ) View more	Positive	30 May 2023
EXPAND (ECTRIMS2022)	Phase 3	Multiple Sclerosis	1,651	Siponimod	tyeagnddrd(nhlkcauqlg) = only 29% of 243 possible EQ-5D health profiles were observed. Conceptual and statistical criteria for computing a single score (EQ-5D health utility index) were not met (Cronbach’s alpha, 0.61; first principal component explained 40%; person separation index, 0.56). EQ-5D item-scored health status correlated only 0.40 with EQ-5D thermometer-scored health status (16% shared variance). EQ-5D item scores remained unchanged in up to 93.5% of patients, when there was change in other related PROs. Results question EQ-5D’s validity and responsiveness klekfgermn (wvhyifelbm ) View more	-	26 Oct 2022
				Placebo
ECTRIMS2022	Not Applicable	COVID-19	-	Fingolimod	qeknqeeoul(qrfakpiqko) = jeufmmxgnx rsfpmrgtir (nptlzvygch ) View more	-	12 Oct 2022
				Siponimod	qeknqeeoul(qrfakpiqko) = ruplssopcm rsfpmrgtir (nptlzvygch ) View more
ECTRIMS2022	Not Applicable	Multiple Sclerosis, Secondary Progressive CYP2C9 genotype	-	Siponimod 2mg	phmcfctfoy(okhgqtgnwd) = A total of 90 patients discontinued the study; 48 prior to and 42 after siponimod exposure kitdgvwiih (mczxczwpus )	-	12 Oct 2022
				Siponimod 1mg
NCT01665144 (EXPAND, Pubmed)	Phase 3	Multiple Sclerosis, Secondary Progressive	779	Siponimod	tutcxwxtxh(hqzboqijvd) = mewgahaypk kvuuoedvjw (pqetezofql )	Positive	31 May 2022
				Placebo	tutcxwxtxh(hqzboqijvd) = yqryrutgbx kvuuoedvjw (pqetezofql )