Delving into the Latest Updates on Evobrutinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

M-2951, MSC 2364447, MSC-2364447

+ [2]

Target

BTK

Action

inhibitors

Mechanism

BTK inhibitors(Tyrosine-protein kinase BTK inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesNervous System Diseases+ [2]

Active Indication-

Inactive Indication

Multiple sclerosis relapseMultiple Sclerosis, Relapsing-RemittingRhabdomyosarcoma+ [2]

Originator Organization

Merck Serono SA

Active Organization-

Inactive Organization

EMD Serono Research & Development Institute, Inc.Merck Healthcare KGaAMerck KGaA

License Organization-

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H27N5O2

InChIKeyQUIWHXQETADMGN-UHFFFAOYSA-N

CAS Registry1415823-73-2

The purpose of this study was to assess the effect of M2951 on the pharmacokinetics (PK) of a combined oral contraceptive [Ethinyl estradiol/Norethisterone (EE/NET)] in healthy female participants.
* Study Duration: up to 46 days
* Treatment Duration: Days 4 to 17 (14 days treatment with M2951); Days 1 and 15 (2 days treatment with Combined Oral Contraceptive [COC])
* Visit Frequency: Participants were resident in the Clinical Research Unit from Day -1 to Day 18.

Start Date24 Aug 2022

Sponsor / Collaborator

Merck Healthcare KGaA

NCT05245396

/ CompletedPhase 1

A Phase I, Single-site, Open-label, Partially Randomized Study to Evaluate the Relative Bioavailability and Pharmacokinetics of Evobrutinib Following Administration of Different Formulations in Healthy Participants

The purpose of this study is to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety and tolerability of evobrutinib after oral administration of immediate release (IR) and modified release (MR) formulations in healthy participants.

Start Date02 Feb 2022

Sponsor / Collaborator

Merck Healthcare KGaA

[+1]

100 Clinical Results associated with Evobrutinib

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100 Translational Medicine associated with Evobrutinib

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100 Patents (Medical) associated with Evobrutinib

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81

Literatures (Medical) associated with Evobrutinib

01 Sep 2025·EUROPEAN JOURNAL OF PHARMACOLOGY

Next generation Bruton's tyrosine kinase inhibitors – characterization of in vitro potency and selectivity

Article

Author: Angst, Daniela ; Cenni, Bruno ; Pulz, Robert

Bruton's tyrosine kinase (BTK) mediates B cell receptor and Fc receptor signaling and is a key regulator of autoimmunity and allergy. A series of novel BTK inhibitors (BTKi) are currently in development for non-oncologic indications with covalent-irreversible (remibrutinib, evobrutinib, tolebrutinib, orelabrutinib), covalent-reversible (rilzabrutinib), and non-covalent reversible (fenebrutinib) binding modes. This study characterizes their in vitro potency and selectivity profiles under the same conditions to minimize assay differences across the different binding modes. Covalent BTKi showed human in vitro blood BTK binding in a time- and concentration-dependent manner with remibrutinib being the most potent and fastest in onset of action. Cellular BTK pathway inhibition was determined in human blood B cells and basophils, and for covalent BTKi correlated well with BTK binding. In contrast to the covalent-irreversible remibrutinib, the non-covalent reversible fenebrutinib showed rapid loss of cellular BTK inhibition after washout. Kinase selectivity was assessed in a binding screen across the human kinome, followed by quantification of binding affinities for a selection of kinases. BTKi ranked in their selectivity as follows (most selective to least): remibrutinib, fenebrutinib, evobrutinib, orelabrutinib, rilzabrutinib and tolebrutinib. These data suggest that next generation BTKi show important differences in their in vitro target binding and selectivity when compared under the same conditions.

01 Sep 2025·DM DISEASE-A-MONTH

Multiple sclerosis updates and the safety and efficacy of Bruton tyrosine kinase inhibitors in it: A systematic review

Article

Author: Shamim, Laiba ; Inban, Pugazhendi ; Patel, Zeel Vishnubhai ; Tekuru, Yogesh ; Prajjwal, Priyadarshi ; Mahato, Priya ; Godinho, Nathan Joseph Silva ; Patel, Prachi Vikrambhai ; Patel, Divyakshi

BACKGROUND:

Multiple sclerosis (MS) is a chronic neurodegenerative and autoimmune disease characterized by CNS inflammation and demyelination. Although current disease-modifying therapies (DMTs) can reduce peripheral immune responses, their impact on CNS-compartmentalized inflammation remains limited. Bruton Tyrosine Kinase inhibitors (BTKis) have emerged as promising oral agents targeting both B cells and microglia.

OBJECTIVE:

To evaluate the safety profiles and effectiveness of two BTK inhibitors- Tolebrutinib and Evobrutinib in the management of relapsing multiple sclerosis.

METHODS:

A literature search was conducted using PubMed, Embase, and Scopus for randomized controlled trials published between 2020 and 2024. Studies comparing Evobrutinib and Tolebrutinib in MS patients were screened and evaluated based on predetermined inclusion and exclusion criteria. Four relevant RCTs were matched and examined in more detail.

RESULTS:

On MRI, both BTK inhibitors showed decreases in gadolinium-enhancing lesions; Tolebrutinib demonstrated dose-dependent efficacy in reducing new Gd-enhancing lesions and T2 lesion counts, with optimal effects at 60 mg daily. Evobrutinib showed dose-dependent decreases in serum neurofilament light (NfL) levels and relapse rates, with twice-daily dosing providing greater BTK inhibition and clinical benefit. Nasopharyngitis, temporary increases in liver enzymes, and mild gastrointestinal symptoms were among the frequent side effects for both agents. The included studies did not report any direct clinical comparisons of CNS penetration or microglial modulation.

CONCLUSION:

With good safety and efficacy profiles in treating relapsing multiple sclerosis, both of the BTKis (Evobrutinib and Tolebrutinib) show promise. Both have promise as oral treatments of the future, but Tolebrutinib might have better effects on the central nervous system. To confirm long-term results and determine their role in progressive MS, more phase III trials are necessary.

11 Apr 2025·ACS Pharmacology & Translational Science

Comprehensive Characterization of Bruton’s Tyrosine Kinase Inhibitor Specificity, Potency, and Biological Effects: Insights into Covalent and Noncovalent Mechanistic Signatures

Review

Author: Servant, Nicole B. ; King, Alastair J. ; Jahic, Mirza ; Darragh, Antonia C. ; Lipner, Justin H. ; Hanna, Andrew M.

Uncovering a drug's mechanism of action and possible adverse effects are critical components in drug discovery and development. Moreover, it provides evidence for why some drugs prove more effective than others and how to design better drugs altogether. Here, we demonstrate the utility of a high-throughput in vitro screening platform along with a comprehensive panel to aid in the characterization of 15 Bruton's tyrosine kinase (BTK) inhibitors that are either approved by the FDA or presently under clinical evaluation. To compare the potency of these drugs, we measured the binding affinity of each to wild-type BTK as well as a clinically relevant resistance mutant of BTK (BTK C481S). In doing so, we discovered a considerable difference in the selectivity and potency of these BTK inhibitors to the wild-type and mutant proteins. Some of this potentially contributes to the adverse effects experienced by patients undergoing therapy using these drugs. Overall, noncovalent BTK inhibitors showed stronger potency for both the wild-type and mutant BTK when compared with that of covalent inhibitors, with the majority demonstrating a higher specificity and less off-target modulation. Additionally, we compared biological outcomes for four of these inhibitors in human cell-based models. As expected, we found different phenotypic profiles for each inhibitor. However, the two noncovalent inhibitors had fewer off-target biological effects when compared with the two covalent inhibitors. This and similar in-depth preclinical characterization of drug candidates can provide critical insights into the efficacy and mechanism of action of a compound that may affect its safety in a clinical setting.

81

News (Medical) associated with Evobrutinib

28 Apr 2025

·pharma.economictimes.indiatimes.com

Germany's Merck KGaA in $3.9 billion deal to buy US biotech firm SpringWorks

Frankfurt: Merck KGaA has struck a deal to buy U.S. biotech company SpringWorks Therapeutics for an equity value of $3.9 billion, as the German company seeks to acquire treatments for rare tumours to boost its cancer drugs business. The family-controlled company said in a statement on Monday the purchase price of $47 per share in cash represents an equity value of about $3.9 billion, equivalent to an enterprise value of $3.4 billion (3.0 billion euros), when SpringWorks' cash holdings are deducted. The deal is one of the largest in years for Merck, but its price tag was 22 per cent lower than the about $60 per share analysts had expected after a Reuters report on February 10 that the companies were in advanced talks. Merck on April 24 lowered price expectations, saying the two companies were in late-stage discussions over a bid of around $47 per SpringWorks share. Merck's shares were down 0.4 per cent in early trade, underperforming the broader German stock market. The deal will be funded with available cash and new debt. It is expected to be accretive to Merck's earnings per share, adjusted for special items, in 2027, said a statement from the German group, based in Darmstadt, near Frankfurt. It added it would still be able to pursue larger transactions. Stamford, Connecticut-based SpringWorks, which listed its shares in New York in 2019, develops drugs to treat cancer and rare types of tumour. It has two products on the market: Ogsiveo with 2024 sales of $172 million to treat desmoid tumours, an aggressive disease affecting soft tissue, as well as Gomekli, which was approved in February to treat NF1-PN, characterised by nerve sheath tumours. "We have the unique opportunity with SpringWorks to establish a leadership position in rare tumours and build a strong foundation for further investments in this area," Peter Guenter, head of healthcare at Merck, said. The transaction will likely close during the second half of 2025, subject to approval of SpringWorks' shareholders and regulatory clearance, Merck added. TRUMP DISRUPTION JP Morgan analyst Anupam Rama previously said the lack of other serious bidders and the challenging macroeconomic environment had probably lowered the valuation. This year had been expected to be stellar for mergers and acqusitions in the sector until the disruption caused by U.S. President Donald Trump's policies, including massive layoffs at the U.S. Food and Drug Administration. That has brought uncertainty to the drug approval process, hampering projected drug sales and affecting valuations. Merck is particularly keen to strengthen its drug development pipeline after high-profile setbacks in late-stage drug trials, including a decision last year to halt development of head and neck cancer drug Xevinapant. A major trial testing multiple sclerosis drug Evobrutinib failed in December 2023. In 2015, the company agreed to buy U.S. lab equipment supplier Sigma-Aldrich for $17 billion, its biggest deal to date. In 2019, Merck acquired U.S. electronics materials manufacturer Versum for around $6.5 billion. (Reporting by Ludwig Burger, Emma-Victoria Farr in Frankfurt and Sabrina Valle in New York; Editing by Kirsten Donovan and Barbara Lewis)

AcquisitionDrug Approval

28 Apr 2025

·pharma.economictimes.indiatimes.com

Germany's Merck KGaA in $3.9 billion deal to buy US biotech firm SpringWorks

Frankfurt: Merck KGaA has struck a deal to buy U.S. biotech company SpringWorks Therapeutics for an equity value of $3.9 billion, as the German company seeks to acquire treatments for rare tumours to boost its cancer drugs business. The family-controlled company said in a statement on Monday the purchase price of $47 per share in cash represents an equity value of about $3.9 billion, equivalent to an enterprise value of $3.4 billion (3.0 billion euros), when SpringWorks' cash holdings are deducted. The deal is one of the largest in years for Merck, but its price tag was 22 per cent lower than the about $60 per share analysts had expected after a Reuters report on February 10 that the companies were in advanced talks. Merck on April 24 lowered price expectations, saying the two companies were in late-stage discussions over a bid of around $47 per SpringWorks share. Merck's shares were down 0.4 per cent in early trade, underperforming the broader German stock market. The deal will be funded with available cash and new debt. It is expected to be accretive to Merck's earnings per share, adjusted for special items, in 2027, said a statement from the German group, based in Darmstadt, near Frankfurt. It added it would still be able to pursue larger transactions. Stamford, Connecticut-based SpringWorks, which listed its shares in New York in 2019, develops drugs to treat cancer and rare types of tumour. It has two products on the market: Ogsiveo with 2024 sales of $172 million to treat desmoid tumours, an aggressive disease affecting soft tissue, as well as Gomekli, which was approved in February to treat NF1-PN, characterised by nerve sheath tumours. "We have the unique opportunity with SpringWorks to establish a leadership position in rare tumours and build a strong foundation for further investments in this area," Peter Guenter, head of healthcare at Merck, said. The transaction will likely close during the second half of 2025, subject to approval of SpringWorks' shareholders and regulatory clearance, Merck added. TRUMP DISRUPTION JP Morgan analyst Anupam Rama previously said the lack of other serious bidders and the challenging macroeconomic environment had probably lowered the valuation. This year had been expected to be stellar for mergers and acqusitions in the sector until the disruption caused by U.S. President Donald Trump's policies, including massive layoffs at the U.S. Food and Drug Administration. That has brought uncertainty to the drug approval process, hampering projected drug sales and affecting valuations. Merck is particularly keen to strengthen its drug development pipeline after high-profile setbacks in late-stage drug trials, including a decision last year to halt development of head and neck cancer drug Xevinapant. A major trial testing multiple sclerosis drug Evobrutinib failed in December 2023. In 2015, the company agreed to buy U.S. lab equipment supplier Sigma-Aldrich for $17 billion, its biggest deal to date. In 2019, Merck acquired U.S. electronics materials manufacturer Versum for around $6.5 billion. (Reporting by Ludwig Burger, Emma-Victoria Farr in Frankfurt and Sabrina Valle in New York; Editing by Kirsten Donovan and Barbara Lewis)

AcquisitionDrug Approval

25 Apr 2025

·pharma.economictimes.indiatimes.com

Germany's Merck says in late-stage discussions to buy SpringWorks for $3.5 billion

Bengaluru: Germany's Merck KGaA said on Thursday it is in late-stage talks to acquire U.S.-based SpringWorks Therapeutics for about $3.5 billion, a deal that could give it access to a recently approved rare disease drug and expand its portfolio of experimental cancer treatments . Merck said that the companies are in discussions on the basis of a price of around $47 per share, which gives a valuation of roughly $3.5 billion, according to Reuters calculations. No final decision has been taken and no legally binding agreement has been entered into, Merck said in a statement. The SpringWorks acquisition would rank as one of the biggest pharma deals for the German healthcare and technology group in recent years, boosting its ongoing efforts to build out its cancer treatment pipeline. In 2015, Merck agreed to buy U.S. lab equipment supplier Sigma-Aldrich for $17 billion. Reuters reported in February that the companies were in advanced talks, which Merck subsequently confirmed. SpringWorks' shares have fallen 17% since then. Shares of SpringWorks settled 9 per cent higher at close, after the Wall Street Journal first reported that Merck is nearing a deal, which could be completed as soon as Monday. The stock was trading closer to $60 in February. SpringWorks, which has a market value of more than $3 billion, did not respond to a Reuters request for comment. The deal could accelerate growth in Merck, particularly as sales of its cancer drug Bavencio slow and multiple sclerosis treatment Mavenclad faces loss of exclusivity, said Barclays analyst Emily Field. The Connecticut-based drugmaker, which went public in 2019, focuses on developing drugs to treat several rare cancers and genetic disorders. Its monotherapy, Ogsiveo , has been approved in the U.S. to treat desmoid tumours - abnormal growth that occurs in connective tissues. In February, the U.S. health regulator approved SpringWorks' genetic disorder drug Gomekli . Merck has recently suffered high-profile setbacks in late-stage drug trials, prompting it to halt development of its head and neck cancer drug xevinapant. A major trial testing multiple sclerosis drug evobrutinib failed in December 2023. (Reporting by Sriparna Roy and Christy Santhosh in Bengaluru, and Sabrina Valle in New York; Editing by Alan Barona)

AcquisitionDrug Approval

100 Deals associated with Evobrutinib

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Rhabdomyosarcoma	Phase 3	United States	Merck KGaA	10 Sep 2019
Rhabdomyosarcoma	Phase 3	Germany	Merck KGaA	10 Sep 2019
Multiple sclerosis relapse	Phase 3	United States	Merck KGaA	26 Aug 2019
Multiple sclerosis relapse	Phase 3	Germany	Merck KGaA	26 Aug 2019
Multiple Sclerosis, Relapsing-Remitting	Phase 3	United States	Merck KGaA	26 Aug 2019
Multiple Sclerosis, Relapsing-Remitting	Phase 3	Germany	Merck KGaA	26 Aug 2019
Systemic Lupus Erythematosus	Phase 2	United States	Merck KGaA	04 Jan 2017
Systemic Lupus Erythematosus	Phase 2	Japan	Merck KGaA	04 Jan 2017
Systemic Lupus Erythematosus	Phase 2	Argentina	Merck KGaA	04 Jan 2017
Systemic Lupus Erythematosus	Phase 2	Bulgaria	Merck KGaA	04 Jan 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04338022 (evolutionRMS 1, CTgov)	Phase 3	Multiple sclerosis relapse	1,124	Teriflunomide (Teriflunomide)	oznlaqkbnw(upfiuezlnu) = jknealltrf wwxeeyayzt (gycajqncqt, qfuscugcrk - adedvzhigf) View more	-	12 Jun 2025
				Evobrutinib (Evobrutinib)	oznlaqkbnw(upfiuezlnu) = wkltpihrwy wwxeeyayzt (gycajqncqt, bcbmjrkkgg - rgvulhocgk) View more
NCT04338061 (evolutionRMS 2, CTgov)	Phase 3	Multiple sclerosis relapse	1,166	Teriflunomide (Teriflunomide)	ouphpprlkj(nglueoszns) = ilbgnjbgsi lvqiegvjtw (zomuhifzwl, wmophjlidl - yecgtjvrps) View more	-	14 Jan 2025
				Evobrutinib (Evobrutinib)	ouphpprlkj(nglueoszns) = qmftrqyhtc lvqiegvjtw (zomuhifzwl, gemoirrnkb - imvjhdzowk) View more
NCT04338061 \| NCT04338022 (evolutionRMS 1, Biospace) Manual	Phase 3	Multiple sclerosis relapse	-	Evobrutinib (evolutionRMS 1)	xbhuqfdvoc(xmjreuwimo) = odcxjnzeev lnkwqcxlpn (htuiyrqohf ) Not Met	Negative	05 Dec 2023
				teriflunomide (evolutionRMS 1)	xbhuqfdvoc(xmjreuwimo) = pxgynkxvyo lnkwqcxlpn (htuiyrqohf ) Not Met
NCT02975349 (Phase 2 OLE, ECTRIMS2023)	Phase 2	Bruton Type Agammaglobulinemia	267	Evobrutinib 25mg QD	jrytezoopv(uwzplfdwqp) = Treatment-emergent adverse events (TEAEs) were reported by 142/164 PwRMS (86.6%) ustwmzxohq (chkhmqnylr ) View more	Positive	30 Sep 2023
				Evobrutinib 75mg BID
NCT02975349 (Phase II, EAN2023)	Phase 2	Rhabdomyosarcoma	45	Evobrutinib 75mg twice-daily	gwhyiypjpu(mglaotxbyh) = dabuqqccll hjysseyymx (kpocsevxfy )	Positive	28 Jun 2023
ACTRIMS2023 \| AAN2023	Not Applicable	Multiple sclerosis relapse	-	Evobrutinib 75 mg twice-daily	kagpojgpux(xraaqhifiv) = yguufuxtnl gnigefrutc (zjrcpeaiuv, 4.5)	-	30 May 2023
				mRNA COVID-19 vaccine	kagpojgpux(xraaqhifiv) = sslveqpfxc gnigefrutc (zjrcpeaiuv, 4.3)
NCT02975349 (AAN2023 \| ACTRIMS2023)	Phase 2	Multiple sclerosis relapse	45	Evobrutinib 75mg twice-daily	nluimhjoia(lobjfnfkqa) = prxhvhrteq nwkyutslfp (wfsvaaxsvc )	-	25 Apr 2023
				mRNA COVID-19 vaccine	nluimhjoia(lobjfnfkqa) = hpwandzajn nwkyutslfp (wfsvaaxsvc )
NCT03233230 \| NCT02975349 \| NCT02975336 (Pubmed)	Phase 2	Multiple Sclerosis \| Rheumatoid Arthritis \| Systemic Lupus Erythematosus	1,083	Evobrutinib	cwnrzgcxbt(vyweqxvxfs) = tjshsxgdyg slsqambjff (mqwnmwzrsw ) View more	-	23 Nov 2022
				Placebo	cwnrzgcxbt(vyweqxvxfs) = iwbzktugky slsqambjff (mqwnmwzrsw ) View more
NCT02975349 (ECTRIMS2022)	Phase 2	Multiple sclerosis relapse	267	Evobrutinib 75mg QD	bwtsqhjmui(cuyqnnahlp) = mkzfzykmzg xwyecdalln (yosvtwjute )	-	12 Oct 2022
				Evobrutinib 75mg BID	bwtsqhjmui(cuyqnnahlp) = yrqxrccdck xwyecdalln (yosvtwjute )
NCT02975349 (ECTRIMS2022)	Phase 2	Multiple sclerosis relapse neurofilament light chain (NfL)	-	EVO 75mg BID	ggmqnewvdn(rdqpgfcssj) = pncedqyxsu ixoixtlswd (xfvnqnfmpd, (30.0 - 79.0))	Positive	12 Oct 2022
				PBO/EVO 25mg QD	ggmqnewvdn(rdqpgfcssj) = jkeomcwads ixoixtlswd (xfvnqnfmpd, (29.0 - 83.0))