Last update 01 Jul 2024

Mavoglurant

Last update 01 Jul 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

AFQ-056, STP 7, STP7

Target

mGluR5

Mechanism

mGluR5 antagonists(Metabotropic glutamate receptor 5 antagonists)

Therapeutic Areas

Other DiseasesNeoplasmsNervous System Diseases

Active Indication

Substance AbuseAlcohol Use DisorderCocaine-Related Disorders+ [2]

Inactive Indication

Dyskinesia, Drug-InducedDyskinesiasFragile X Syndrome+ [7]

Originator Organization

Novartis Pharma AG

Active Organization

Stalicla SAStartup

National Institute on Drug Abuse

National Institute on Alcohol Abuse & Alcoholism

Inactive Organization

Novartis Pharmaceuticals Corp.

Novartis AG

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (EU)

Structure

Molecular FormulaC19H23NO3

InChIKeyZFPZEYHRWGMJCV-ZHALLVOQSA-N

CAS Registry543906-09-8

Clinical Trials associated with Mavoglurant

NCT06136195 / Not yet recruitingPhase 2IIT

Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers

The purpose of this research study is to find out about the effects of a drug called mavoglurant on alcohol consumption.

Start Date01 Jul 2024

Sponsor / Collaborator

Yale University

[+1]

NCT06273540 / RecruitingPhase 1

Phase 1, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess Potential Interactions Between Intravenous Cocaine and Oral STP7

This is a double-blind, placebo-controlled, parallel group study to compare the effects of STP7 (mavoglurant) vs placebo control on i.v. cocaine's physiological and subjective effects in non-treatment seeking, cocaine-experienced males or females participants between 18 and 59 years of age.
The primary objective of this study is to determine if there are clinically meaningful interactions between oral STP7 (mavoglurant) treatment concurrent with 20 and 40 mg i.v. cocaine infusions by measuring adverse events and cardiovascular responses including heart rate, blood pressure, and electrocardiogram (including corrected QT interval).
The secondary objectives are:
To evaluate whether administration of STP7 (mavoglurant) alters the pharmacokinetics of cocaine and/or its major metabolite, benzoylecgonine.
To determine the pharmacokinetic of STP7 (mavoglurant) administered at a dose of 200 mg twice a day.
To evaluate whether STP7 (mavoglurant) treatment alters the subjective effects of cocaine measured by Visual Analog Scales (VAS) and Brief Substance Craving Scale (BSCS).

Start Date15 Apr 2024

Sponsor / Collaborator

Stalicla SAStartup

[+1]

NCT05203965 / RecruitingEarly Phase 1IIT

Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant

The purpose of this study is to evaluate the role of Mavoglurant in clarifying the neurobiology of alcoholism risk. This is a one-site, randomized, within subjects, counterbalanced double-blind study of a single dose (200mg) of Mavoglurant and placebo.

Start Date17 May 2022

Sponsor / Collaborator

Yale University

[+1]

100 Clinical Results associated with Mavoglurant

100 Translational Medicine associated with Mavoglurant

100 Patents (Medical) associated with Mavoglurant

Literatures (Medical) associated with Mavoglurant

04 Jan 2024·Brain : a journal of neurology

Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity

Article

Author: Kim, Byungchan ; Olsson, Roger ; Hakon, Jakob ; Ruscher, Karsten ; Moyanova, Slavianka ; Di Menna, Luisa ; Bauer, Adam Q ; Mastroiacovo, Federica ; Sjölund, Carin ; Wieloch, Tadeusz ; Quattromani, Miriana J ; Nicoletti, Ferdinando ; Englund, Elisabet ; Talhada, Daniela

Abstract:

Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischaemia.Using multiple behavioural tests, we observed that treatment with negative allosteric modulators (NAMs) of mGluR5 (MTEP, fenobam and AFQ056) for 12 days, starting 2 or 10 days after stroke, restored lost sensorimotor functions, without diminishing infarct size. Recovery was evident within hours after initiation of treatment and progressed over the subsequent 12 days. Recovery was prevented by activation of mGluR5 with the positive allosteric modulator VU0360172 and accelerated in mGluR5 knock-out mice compared with wild-type mice. After stroke, multisensory stimulation by enriched environments enhanced recovery, a result prevented by VU0360172, implying a role of mGluR5 in enriched environment-mediated recovery. Additionally, MTEP treatment in conjunction with enriched environment housing provided an additive recovery enhancement compared to either MTEP or enriched environment alone. Using optical intrinsic signal imaging, we observed brain-wide disruptions in resting-state functional connectivity after stroke that were prevented by mGluR5 inhibition in distinct areas of contralesional sensorimotor and bilateral visual cortices. The levels of mGluR5 protein in mice and in tissue samples of stroke patients were unchanged after stroke.We conclude that neuronal circuitry subserving sensorimotor function after stroke is depressed by a mGluR5-dependent maladaptive plasticity mechanism that can be restored by mGluR5 inhibition. Post-acute stroke treatment with mGluR5 NAMs combined with rehabilitative training may represent a novel post-acute stroke therapy.

01 Mar 2024·The Journal of clinical investigation

Effects of AFQ056 on language learning in fragile X syndrome

Article

Author: Cudkowicz, Merit ; Hagerman, Randi ; Veenstra-VanderWeele, Jeremy ; Harkey, Brittney ; Klingner, Elizabeth ; Berry-Kravis, Elizabeth ; Coffey, Christopher S ; Pearson, Brenda ; Abbeduto, Leonard ; Huff, Trevis ; Tassone, Flora ; Costigan, Michele ; Long, Jeff ; Erickson, Craig A ; Kaufmann, Walter E ; Fedler, Janel ; Staley, Kevin ; Ecklund, Dixie ; Klements, David ; Ethridge, Lauren ; Moshinsky, Michael ; Friedmann, Katherine ; Hoffmann, Anne ; McDuffie, Andrea ; Hessl, David ; Bullard, Lauren

BACKGROUNDFXLEARN, the first-ever large multisite trial of effects of disease-targeted pharmacotherapy on learning, was designed to explore a paradigm for measuring effects of mechanism-targeted treatment in fragile X syndrome (FXS). In FXLEARN, the effects of metabotropic glutamate receptor type 5 (mGluR5) negative allosteric modulator (NAM) AFQ056 on language learning were evaluated in 3- to 6-year-old children with FXS, expected to have more learning plasticity than adults, for whom prior trials of mGluR5 NAMs have failed.METHODSAfter a 4-month single-blind placebo lead-in, participants were randomized 1:1 to AFQ056 or placebo, with 2 months of dose optimization to the maximum tolerated dose, then 6 months of treatment during which a language-learning intervention was implemented for both groups. The primary outcome was a centrally scored videotaped communication measure, the Weighted Communication Scale (WCS). Secondary outcomes were objective performance-based and parent-reported cognitive and language measures.RESULTSFXLEARN enrolled 110 participants, randomized 99, and had 91 who completed the placebo-controlled period. Although both groups made language progress and there were no safety issues, the change in WCS score during the placebo-controlled period was not significantly different between the AFQ056 and placebo-treated groups, nor were there any significant between-group differences in change in any secondary measures.CONCLUSIONDespite the large body of evidence supporting use of mGluR5 NAMs in animal models of FXS, this study suggests that this mechanism of action does not translate into benefit for the human FXS population and that better strategies are needed to determine which mechanisms will translate from preclinical models to humans in genetic neurodevelopmental disorders.TRIAL REGISTRATIONClincalTrials.gov NCT02920892.FUNDING SOURCESNeuroNEXT network NIH grants U01NS096767, U24NS107200, U24NS107209, U01NS077323, U24NS107183, U24NS107168, U24NS107128, U24NS107199, U24NS107198, U24NS107166, U10NS077368, U01NS077366, U24NS107205, U01NS077179, and U01NS077352; NIH grant P50HD103526; and Novartis IIT grant AFQ056X2201T for provision of AFQ056.

01 Sep 2022·Pharmacology, biochemistry, and behavior

Clinical investigations of compounds targeting metabotropic glutamate receptors

Review

Author: Smith, Jodi L ; Pandey, Kamal P ; Witkin, Jeffrey M

Pharmacological modulation of glutamate has long been considered to be of immense therapeutic utility. The metabotropic glutamate receptors (mGluRs) are potential targets for safely altering glutamate-driven excitation. Data support the potential therapeutic use of mGluR modulators in the treatment of anxiety, depression, schizophrenia, and other psychiatric disorders, pain, epilepsy, as well as neurodegenerative and neurodevelopmental disorders. For each of the three mGluR groups, compounds have been constructed that produce either potentiation or functional blockade. PET ligands for mGlu5Rs have been studied in a range of patient populations and several mGlu5R antagonists have been tested for potential efficacy in patients including mavoglurant, diploglurant, basimglurant, GET 73, and ADX10059. Efficacy with mGlu5R antagonists has been reported in trials with patients with gastroesophageal reflux disease; data from patients with Parkinson's disease or Fragile X syndrome have not been as robust as hoped. Fenobam was approved for use as an anxiolytic prior to its recognition as an mGlu5R antagonist. mGlu2/3R agonists (pomaglumated methionil) and mGlu2R agonists (JNJ-40411813, AZD 8529, and LY2979165) have been studied in patients with schizophrenia with promising but mixed results. Antagonists of mGlu2/3Rs (decoglurant and TS-161) have been studied in depression where TS-161 has advanced into a planned Phase 2 study in treatment-resistant depression. The Group III mGluRs are the least developed of the mGluR receptor targets. The mGlu4R potentiator, foliglurax, did not meet its primary endpoint in patients with Parkinson's disease. Ongoing efforts to develop mGluR-targeted compounds continue to promise these glutamate modulators as medicines for psychiatric and neurological disorders.

News (Medical) associated with Mavoglurant

28 Jun 2024

·www.globenewswire.com

STALICLA publishes pioneering phase 1b data on precision treatment for autism spectrum disorder in Biomedicines

STALICLA’s precision psychiatry study highlights strong EEG-based target engagement of STP1 treatment in defined subgroup of patients with autism and numerical improvement in core symptoms June 27, 2024 – STALICLA SA, a Swiss neuro precision biotech company dedicated to developing precision medicine-based treatments for neuropsychiatric and neurodevelopmental disorders, today announced the publication of a landmark phase 1b study with STP1, a novel combination therapy tailored for the treatment of a clinically and biologically defined subgroup of patients with autism spectrum disorder (ASD), named ASD Phenotype 1 (ASD-Phen1). The results of the study were published in the peer-reviewed journal Biomedicines, in an article titled “Safety, Tolerability, and EEG-Based Target Engagement of STP1 (PDE3,4 Inhibitor and NKCC1 Antagonist) in a Randomized Clinical Trial in a Subgroup of Patients with ASD”. Lynn Durham, CEO of STALICLA, highlighted: “This study marks a significant milestone in the advancement of precision medicine for ASD. It is a first-of-its-kind stratification-based approach for clinical development in neurodevelopmental disorders, demonstrating the potential of precision medicine in ASD.” The randomized, double-blind, placebo-controlled phase 1b clinical trial evaluated the safety and tolerability of STP1, a combination of ibudilast and bumetanide, in ASD-Phen1 patients. The clinical trial (registered at clinicaltrials.gov NCT04644003), involved two 14-day treatment phases of ASD-Phen1 patients receiving STP1 or placebo. The results showed that STP1 was well-tolerated with no significant adverse effects reported. Significant and dose-related reductions in gamma power were observed in the whole brains of patients taking STP1, particularly in regions associated with executive function and memory. Additionally, STP1 increased alpha 2 power in frontal and occipital regions, while improving habituation and neural synchronization to auditory chirps. Dr. Craig A. Erickson, Associate Professor, UC Department of Psychiatry and Behavioral Neuroscience, Cincinnati Children’s Hospital Medical Center, and the principal investigator of the study, remarked: “The electrophysiological signals from this study are remarkable and represent the strongest early trial target engagement signals our lab has seen in the autism field.” Dr. Laura Pérez-Cano, Head of Discovery at STALICLA and co-author of the study, added: “These findings not only highlight the potential of STP1 as a therapeutic option for ASD-Phen1 patients but also underscore the importance of combining biologically-based patient stratification with quantifiable outcome measures such as EEG that can then be correlated with behavioral measures.” By focusing on a biologically defined subgroup of ASD patients, STALICLA is moving closer to making personalized treatment options a reality for patients with ASD. This approach has the potential to revolutionize the treatment of ASD and other neuropsychiatric conditions. STALICLA is a global, clinical-stage biotechnology company focused on advancing precision medicine for brain disorders. The company has developed a unique neuro precision development platform, DEPI, supported by clinical validation in a first indication: Autism Spectrum Disorder. Its lead neurodevelopmental disorder asset, STP1, is entering Phase 2 trials. Its lead neuropsychiatry asset, STP7 (Mavoglurant), fully funded by the US government, will soon be Phase 3 ready for Cocaine Use Disorder. ‎ The content above comes from the network. if any infringement, please contact us to modify.

Clinical Result

08 May 2024

·www.globenewswire.com

STALICLA initiates U.S. Phase 3 enabling DDI study of STP7 (Mavoglurant) to treat cocaine use disorder

May 2, 2024 – STALICLA SA, a late-stage biotechnology company specializing in precision medicine for brain disorders, announces the First Patient First Visit (FPFV) for the company's drug-drug interaction (DDI) study of STP7 (Mavoglurant), an mGluR5 negative allosteric modulator, licensed to STALICLA by Novartis. The DDI study is the last regulatory requirement in a comprehensive Phase 2 program and completion is expected to trigger initiation of a Phase 3 study in the U.S. in 2025. Lynn Durham, CEO and Founder of STALICLA said, “This DDI study unlocks the opportunity under our Cooperative Research and Development Agreement with the U.S. NIH National Institute of Drug Abuse (NIDA) to begin Phase 3 trials for STP7 in 2025 to address the high unmet medical need of cocaine abuse globally. Results from successfully completed Phase 2 studies for cocaine use disorder (CUD) showed highly convincing and unprecedented efficacy results including increase in abstinence from cocaine use and reduction in co-morbid dependencies such as alcohol abuse with STP7 (Mavoglurant). In addition, STALICLA is investigating alternative therapeutic indications for STP7 (Mavoglurant) to benefit patients with other CNS conditions.” STP7 (Mavoglurant) is the most clinically advanced negative allosteric modulator of the glutamate receptor 5 (mGluR5 NAM). As well as its role in addiction pathophysiology, mGluR5 has been implicated in mood disorders and neurodevelopmental disorders such as Fragile X and autism spectrum disorder. Comprehensive clinical studies by Novartis of STP7 (Mavoglurant) to date have included over 1800 adults for up to 2 years, demonstrating good safety and tolerability and significant reduction in cocaine use and positioning STP7 (Mavoglurant) as a strong candidate therapy for substance use and other CNS disorders. STALICLA SA is a Swiss clinical-stage biopharmaceutical company, pioneering precision treatment in neurodevelopmental and neuropsychiatric disorders. Its AI-driven precision neuro medicine platform has allowed to identify two precision small molecule drug candidates for autism spectrum disorder, STP1 and STP2, both planned to enter Phase 2 trials in 2024. Following the in-licensing of Mavoglurant from Novartis in 2023, STALICLA has also established an advanced mGluR5 NAM platform offering multi-faceted late-stage clinical development opportunities broadening STALICLA’s scope to address wider CNS disease unmet needs. For more information, please visit: www.stalicla.com. The content above comes from the network. if any infringement, please contact us to modify.

Phase 3Clinical Result

03 Apr 2024

·www.pharmaceutical-technology.com

EC approves Bristol Myers Squibb’s Reblozyl for first-line MDS treatment

The approval for Bristol Myers Squibb’s Reblozyl is applicable in all the EU member states. Katherine Welles / Shutterstock.com. The European Commission (EC) has granted expanded approval for Bristol Myers Squibb ‘s (BMS) Reblozyl (luspatercept) as a first-line treatment for adults with transfusion-dependent anaemia associated with very low, low and intermediate-risk myelodysplastic syndromes (MDS). The decision is applicable in all the member states of the European Union (EU). The EC’s expanded approval is based on the results from the open-label, randomised Phase III COMMANDS study. The trial assessed the efficacy and safety of Reblozyl compared to epoetin alfa, an erythropoiesis-stimulating agent, in treating anaemia due to MDS. It included subjects who needed red blood cell (RBC) transfusions and had not previously received erythropoiesis-stimulating agents. See Also: Alexion’s Voydeya gains FDA approval for extravascular haemolysis Novartis gets grant for treatment of cocaine use disorder using mavoglurant Reblozyl significantly outperformed epoetin alfa in achieving concurrent RBC transfusion independence and a rise in haemoglobin levels – the study’s primary endpoint. Safety results were in line with previous studies on MDS, with no significant differences in progression to acute myeloid leukaemia or total deaths between the study arms. This approval is the fourth indication authorised for Reblozyl in Europe, positioning it as a first-in-class treatment for people with disease-related anaemia and the first therapy to demonstrate superior efficacy versus epoetin alfa in lower-risk MDS (LR-MDS). Reblozyl is a product of a global collaboration and is co-promoted in North America by Merck (MSD), following its acquisition of Acceleron Pharma in November 2021. It has also been approved in the US and Japan for the first-line treatment of anaemia associated with LR-MDS. Bristol Myers Squibb European Markets senior vice-president and head Monica Shaw stated: “With this approval for Reblozyl as a first-line treatment for anaemia in adults with LR MDS, more patients in the EU will have the potential to become transfusion independent for longer periods compared to current options available. “This milestone underscores our ongoing commitment to developing new options for patients with disease-related anaemia.” Last month, the EC approved BMS’ Abecma (idecabtagene vicleucel; ide-cel) to treat adults with relapsed and refractory multiple myeloma .

Drug ApprovalPhase 3Clinical Result

100 Deals associated with Mavoglurant

External Link

KEGG	Wiki	ATC	Drug Bank
-	Mavoglurant	-	DB13004

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Substance Abuse	Phase 3	US	National Institute on Drug Abuse	08 Mar 2023
Substance Abuse	Phase 3	US	Stalicla SAStartup	08 Mar 2023
Fragile X Syndrome	Phase 3	US	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	AU	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	BE	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	DK	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	FR	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	DE	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	IL	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	IT	Novartis Pharmaceuticals Corp.	01 Nov 2011

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02920892 (CTgov)	Phase 2	Fragile X Syndrome	110	placebo+AFQ056 (Placebo Comparator: Double-Blind Placebo With Language Intervention)	gpsotebguq(wevgkfguep) = hswuyecpjs qlqqoxjwwn (updlzvdnju, reqyaqxpet - pzxwqpoynp) View more	-	10 Oct 2023
				AFQ056 (Experimental: Double-Blind AFQ056 With Language Intervention)	gpsotebguq(wevgkfguep) = tknthyqupt qlqqoxjwwn (updlzvdnju, tyfadnfebm - jyrzcvvnxi) View more
NCT03242928 (CTgov)	Phase 2	Cocaine-Related Disorders \| Systemic Carnitine Deficiency	68	AFQ056 (AFQ056)	qoiyosvkti(mylcjaccyg) = pmlepwysbp xsqeookxto (qrcyihmwzg, evkgczhznk - ihiqxbmtop) View more	-	04 Feb 2021
				placebo (Placebo)	qoiyosvkti(mylcjaccyg) = puzulsksjh xsqeookxto (qrcyihmwzg, ofjwdtabgp - ttefdfuooy) View more
NCT01348087 (Pubmed \| Sci Rep) Manual	Phase 2	Fragile X Syndrome	267	mavoglurant	jdzkfykstr(ejkafmkvie) = hjirfvzjrz eerhexidlt (ooqujgbgpv ) View more	Negative	19 Nov 2018
NCT01813019 (Pubmed \| Adv Ther) Manual	Phase 2	Obsessive-Compulsive Disorder	50	mavoglurant	qelxfibrle(rxfoxbhifo) = gujfswfgoe dnedgskpet (pikguhrmgr ) View more	Negative	01 Feb 2017
				Placebo	qelxfibrle(rxfoxbhifo) = fjceopkrbq dnedgskpet (pikguhrmgr ) View more
NCT01813019 (CTgov)	Phase 2	Obsessive-Compulsive Disorder	50	Placebo (Placebo)	xexgpzzuks(vthedoaihu) = yfyxcfilym wzmtywojcd (aagsikmkmh, ejoailatnf - jagfkpzxfj) View more	-	21 Jul 2016
				AFQ056 (AFQ056)	xexgpzzuks(vthedoaihu) = owfyuzwwph wzmtywojcd (aagsikmkmh, aiggrttylj - pftolecgoz) View more
NCT01385592 (Pubmed) Manual	Phase 2	Dyskinesia, Drug-Induced \| Parkinson Disease	-	Mavoglurant	rajihglzjt(axdxlfshof) = did not reach statistical significance rqexxdgpmn (zluioktfkt )	Negative	01 Jul 2016
				Placebo
NCT01253629 (Pubmed \| Sci Transl Med) Manual	Phase 2	Fragile X Syndrome	314	Mavoglurant	nbcjfihspq(esqpdfggal) = Neither of the studies achieved skxllxmvfw (rdjewuayvq )	Negative	13 Jan 2016
				Placebo
NCT01357239 (CTgov)	Phase 2	Fragile X Syndrome	139	placebo	ndhybqfesf(dvladrhgso) = jrfzgqatlw czobiixxma (umtipafjpz, yxnktqdcyi - ogednansad) View more	-	12 May 2015
NCT01019473 (Pubmed \| Mov Disord) Manual	Phase 2	Chorea \| Huntington Disease	42	AFQ056	mbsdkojxnh(negsyqhztk) = no improvement odqceltmnz (voohrcmoou ) View more	Negative	01 Mar 2015
				Placebo
NCT00718341 (Pubmed \| Sci Transl Med) Manual	Phase 2	Fragile X Syndrome	30	AFQ056	oihrgwbkov(qrthhmkrrf): P-Value = <0.001 View more	Positive	05 Jan 2011
				Placebo

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