Delving into the Latest Updates on Migalastat Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1-Deoxygalactonojirimycin, 1-Deoxygalactostatin, galacto-DNJ HCl

+ [11]

Target

GALA

Mechanism

GLA stimulants(α-Galactosidase stimulants)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesCongenital Disorders+ [3]

Active Indication

Fabry DiseaseKidney Failure, Chronic

Inactive Indication-

Originator Organization

Amicus Therapeutics, Inc.

Active Organization

Amicus Therapeutics, Inc.Handok Carlos Medical Co. Ltd.Amicus Therapeutics Europe Ltd.

+ [2]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

EU (25 May 2016),

Fabry Disease

RegulationOrphan Drug (US), Orphan Drug (KR), Orphan Drug (AU), Overseas New Drugs Urgently Needed in Clinical Settings (CN), Accelerated Approval (US), Fast Track (US)

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Structure

Molecular FormulaC6H14ClNO4

InChIKeyZJIHMALTJRDNQI-OLALXQGDSA-N

CAS Registry75172-81-5

Author: Djurkovic, Filip ; Ferjancic, Zorana ; Trmcic, Milena ; Vulovic, Bojan ; Pavlovic, Milos ; Djurdjevic Djelmas, Aleksandra ; Prodanovic, Radivoje ; Bihelovic, Filip ; Vignuzzi, Marco ; Matovic, Radomir ; Saicic, Radomir N ; Sladic, Dusan ; Kalicanin, Nevena ; Jankovic, Aleksandar ; Vallet, Thomas ; Zlatovic, Mario

We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC₉₀ = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections.

01 Nov 2024·BIODRUGS

Biochemical Amenability in Fabry Patients Under Chaperone Therapy—How and When to Test?

Article

Author: Brand, Eva ; Menke, Elise Raphaela ; Lenders, Malte

AIM:

Current recommendations for Fabry disease include α-galactosidase A (AGAL) activity measurements to assess the biochemical response in migalastat-treated patients. Owing to contradictory data from laboratories, we aimed to analyze why AGAL activity measures from dried blood spots (DBS) often fail to detect migalastat-mediated enzymatic activity increases in treated patients.

METHODS:

43 patients with 58 visits under migalastat were consecutively recruited. Enzymatic AGAL activities were measured from DBS and peripheral blood mononuclear cells (PBMCs). Migalastat concentrations in sera were determined using modified serum-mediated inhibition assays to assess C_max and serum half-life. Results were set in relation to the time of last migalastat intake and blood sampling to assess an optimal timepoint for AGAL activity measures.

RESULTS:

DBS-based AGAL activity measurements of 21 (42.0%) amenable patients were below the limit of detection. Serum samples from migalastat-treated patients showed significant AGAL inhibition, depending on the time between migalastat intake and blood sampling (r² = 0.8140, p < 0.0001). Migalastat concentrations were determined in serum samples confirming a C_max at 3 h and a serum half-life of 4 h. At 24 h after intake, migalastat clearance was significantly associated with renal function (r² = 0.3135, p = 0.0102). Enzymatic AGAL activities were higher in samples from DBS and PBMCs 24 h after migalastat intake (both p < 0.05).

CONCLUSION:

The optimal time for enzymatic AGAL activity measurement in migalastat-treated patients appears to be 24 h after the last migalastat intake. Since migalastat is a competitive inhibitor of AGAL, enzymatic AGAL activity measurements should be better performed from PBMCs to reduce migalastat-mediated interferences.

27 Sep 2024·JOURNAL OF EXPERIMENTAL BOTANY

Raffinose catabolism enhances maize waterlogging tolerance by stimulating adventitious root growth and development

Article

Author: Zhao, Tianyong ; Yan, Dong ; Li, Dan ; Zhang, Yumin ; Dirk, Lynnette M A ; Gao, Yu ; Downie, A Bruce

Abstract:

Raffinose mitigates plant heat, drought, and cold stresses; however, whether raffinose contributes to plant waterlogging tolerance is unknown. The maize raffinose synthase mutant zmrafs-1 had seedlings that lack raffinose, generated fewer and shorter adventitious roots, and were more sensitive to waterlogging stress, while overexpression of the raffinose synthase gene, ZmRAFS, increased raffinose content, stimulated adventitious root formation, and enhanced waterlogging tolerance of maize seedlings. Transcriptome analysis of null segregant seedlings compared with zmrafs-1, particularly when waterlogged, revealed that the expression of genes related to galactose metabolism and the auxin biosynthetic pathway were up-regulated by raffinose. Additionally, indole-3-acetic acid content was significantly decreased in zmrafs-1 seedlings and increased in ZmRAFS-overexpressing seedlings. Inhibition of the hydrolysis of raffinose by 1-deoxygalactonojirimycin decreased the waterlogging tolerance of maize seedlings, the expression of genes encoding proteins related to auxin transport-related genes, and the indole-3-acetic acid level in the seedlings, indicating that the hydrolysis of raffinose is necessary for maize waterlogging tolerance. These data demonstrate that raffinose catabolism stimulates adventitious root formation via the auxin signaling pathway to enhance maize waterlogging tolerance.

40

News (Medical) associated with Migalastat Hydrochloride

17 Oct 2024

·endpts.com

Amicus stock jumps after resolution of Galafold patent litigation against Teva

Amicus Therapeutics resolved a patent dispute with Teva on Thursday, allowing Teva to launch a generic version of its Fabry disease treatment Galafold in 2037. Leerink Partners analysts called it a “near best-case outcome” for Amicus, considering some Galafold patents begin to expire in the late 2020s. Amicus’ stock $FOLD was up nearly 15% on Thursday afternoon following the announcement. Galafold, also known as migalastat, was approved in 2018 for Fabry disease, a rare genetic disorder that can lead to kidney and heart failure. The drug generated $387.8 million in 2023, up 18% from 2022. In court documents, Amicus has called it the “cornerstone” of its portfolio. Amicus announced on Thursday that it will grant Teva a license to market generic Galafold in the US on Jan. 30, 2037, pending FDA approval. The deal will settle ongoing Galafold patent litigation between the companies in Delaware federal court, first filed in 2022. The license agreement is subject to review by the FTC and DOJ. “This potentially provides the company with another 10+ years of exclusivity in the US for Galafold, which continues to launch well and is on track for >$450M in sales this year,” Leerink analysts said in a note to investors on Thursday. On its most recent earnings call, Amicus touted Galafold’s 61 patents listed in the FDA’s Orange Book. CBO Sébastien Martel said Amicus was “confident that with our strong IP protection, Galafold has a long runway well into the next decade,” according to an AlphaSense transcript. The settlement doesn’t resolve patent litigation against Aurobindo, which remains ongoing, and a stay will remain in place in litigation against Lupin.

Patent InfringementDrug ApprovalLicense out/in

17 Oct 2024

·www.globenewswire.com

Amicus Therapeutics Announces Settlement of Galafold® (migalastat) Patent Litigation with Teva

Company Grants Teva a License to Market Generic Galafold® Beginning in January 2037PRINCETON, N.J., Oct. 17, 2024 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq: FOLD) today announced that it has entered into a License Agreement (Agreement) with Teva Pharmaceuticals USA, Inc. and Teva Pharmaceuticals, Inc. (collectively Teva). This Agreement resolves the patent litigation brought by Amicus in response to Teva’s Abbreviated New Drug Application (ANDA) seeking approval to market a generic version of GALAFOLD® (migalastat) 123mg capsules prior to expiration of the applicable patents. Pursuant to the terms of the Agreement, Amicus will grant Teva a license to market its generic version of GALAFOLD® in the United States beginning on January 30, 2037, if approved by the U.S. Food and Drug Administration (FDA) and unless certain limited circumstances customarily included in these types of agreements occur. In accordance with the Agreement, the parties will terminate all ongoing Hatch-Waxman litigation between Amicus and Teva regarding GALAFOLD® patents pending in the U.S. District Court for the District of Delaware. The litigation will continue against Aurobindo1 as the remaining active party and the litigation stay remains in place for Lupin2. As required by law, the companies will submit the confidential license agreement to the U.S. Federal Trade Commission and the U.S. Department of Justice for review. About Amicus Therapeutics Amicus Therapeutics (Nasdaq: FOLD) is a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel high-quality medicines for people living with rare diseases. With extraordinary patient focus, Amicus Therapeutics is committed to advancing and expanding a pipeline of cutting-edge, first- or best-in-class medicines for rare diseases. For more information please visit the company’s website at www.amicusrx.com, and follow on X and LinkedIn. Forward Looking StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including but not limited to, statements concerning: the terms of the settlement agreement with Teva, expectations regarding the impact of the settlement agreement and submission of the settlement agreement for review to the United States Federal Trade Commission and the United States Department of Justice. The company cautions that forward-looking statements are inherently uncertain. Although the company believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, the forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those expressed or implied in the forward-looking statements due to various risks and uncertainties, including the unfavorable outcome of other litigation, including so-called "Paragraph IV" litigation and other patent litigation, related to GALAFOLD, which may lead to competition from generic drug manufacturers; the outcome of any review of the settlement agreement by the United States Federal Trade Commission and United States Department of Justice; the U.S. FDA may approve Teva's ANDA significantly in advance of the entry date; and those risks and uncertainties described under the heading "Risk Factors" in the company's most recent Annual Report on Form 10-K for the year ended December 31, 2023, and on Form 10-Q for the quarter ended June 30, 2024. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update this news release to reflect events or circumstances after the date hereof. CONTACT: Investors:Amicus TherapeuticsAndrew FaughnanVice President, Investor Relationsafaughnan@amicusrx.com (609) 662-3809 Media:Amicus TherapeuticsDiana MooreHead of Global Corporate Affairs and Communicationsdmoore@amicusrx.com (609) 662-5079 FOLD–G 1 Aurobindo Pharma LTD and Aurobindo Pharma USA, Inc.2 Lupin LTD and Lupin Pharmaceuticals, Inc.

License out/inPatent Infringement

03 Sep 2024

·www.globenewswire.com

Amicus Therapeutics Announces Participation at the SSIEM 2024 Annual Symposium

PRINCETON, N.J., Sept. 03, 2024 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq: FOLD), today announced that five posters across its development programs will be included at the Society for the Study of Inborn Errors of Metabolism (SSIEM) 2024 Annual Symposium, being held September 3-6, 2024 in Porto, Portugal. Poster Sessions: Fabry Disease: Abstract Title: FollowME Fabry Pathfinders registry: patient-reported outcomes in a cohort of patients on migalastat treatment for at least two years (Poster #21180) Presenter: Aleš Linhart, D.Sc., Charles University and General University Hospital in Prague, Prague, Czech RepublicPoster Session: Wednesday, September 4, 6:15 – 8:15 p.m. WETLocation: Poster Room, Rosa Mota Pavilion Abstract Title: Quality of life of migalastat-treated adolescents with Fabry disease: results from the ASPIRE study and open-label extension (Poster #21202) Presenter: Amarilis Sanchez-Valle, MD, University of South Florida Health, Tampa, U.S.A.Poster Session: Wednesday, September 4, 6:15 – 8:15 p.m. WETLocation: Poster Room, Rosa Mota Pavilion Abstract Title: Exploring the journey of patients living with Fabry disease in Poland (Poster #20789) Presenter: Anna Moskal, The Association of Families with Fabry Disease, Wroclaw, PolandPoster Session: Wednesday, September 4, 6:15 – 8:15 p.m. WETLocation: Poster Room, Rosa Mota Pavilion Pompe Disease: Abstract Title: Post-baseline outcomes of the UK Early Access to Medicines Scheme registry for cipaglucosidase alfa plus miglustat in late-onset Pompe disease (Poster #20863) Presenter: Elaine Murphy, MD, University College London Hospitals, London, U.K.Poster Session: Wednesday, September 4, 6:15 – 8:15 p.m. WETGuided Poster Walk: Thursday, September 5, 12:10 – 1:40 p.m. WETLocation: Poster Room, Rosa Mota Pavilion Abstract Title: Miglustat: a first-in-class enzyme stabilizer for late-onset Pompe disease (Poster #20873) Presenter: Mark Roberts, MD, Salford Royal NHS Foundation Trust, Greater Manchester Neurosciences Centre, Manchester, U.K.Poster Session: Wednesday, September 4, 6:15 – 8:15 p.m. WETLocation: Poster Room, Rosa Mota Pavilion For more information on the SSIEM 2024 Annual Symposium, please visit ssiem2024.org. About Amicus Therapeutics Amicus Therapeutics (Nasdaq: FOLD) is a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel high-quality medicines for people living with rare diseases. With extraordinary patient focus, Amicus Therapeutics is committed to advancing and expanding a pipeline of cutting-edge, first- or best-in-class medicines for rare diseases. For more information please visit the company’s website at www.amicusrx.com, and follow on X and LinkedIn. CONTACTS: Investors: Amicus Therapeutics Andrew Faughnan Vice President, Investor Relations afaughnan@amicusrx.com(609) 662-3809 Media: Amicus Therapeutics Diana Moore Head of Global Corporate Communications dmoore@amicusrx.com(609) 662-5079 FOLD–G

100 Deals associated with Migalastat Hydrochloride

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KEGG	Wiki	ATC	Drug Bank
D05031	Migalastat Hydrochloride	A16AX	DB05018

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Fabry Disease	EU	Amicus Therapeutics Europe Ltd.	25 May 2016
Fabry Disease	IS	Amicus Therapeutics Europe Ltd.	25 May 2016
Fabry Disease	LI	Amicus Therapeutics Europe Ltd.	25 May 2016
Fabry Disease	NO	Amicus Therapeutics Europe Ltd.	25 May 2016

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Kidney Failure, Chronic	Phase 3	US	Amicus Therapeutics, Inc.	31 Oct 2022
Kidney Failure, Chronic	Phase 3	JP	Amicus Therapeutics, Inc.	31 Oct 2022
Kidney Failure, Chronic	Phase 3	AU	Amicus Therapeutics, Inc.	31 Oct 2022
Kidney Failure, Chronic	Phase 3	FR	Amicus Therapeutics, Inc.	31 Oct 2022
Kidney Failure, Chronic	Phase 3	PT	Amicus Therapeutics, Inc.	31 Oct 2022
Kidney Failure, Chronic	Phase 3	ES	Amicus Therapeutics, Inc.	31 Oct 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ISN WCN2024	Not Applicable	-	-	Migalastat	cxxfejovdx(xjsltbtmya) = cvphfmnmyh voryacvmze (hlrpvzmhik, 75 - 95) View more	-	01 Apr 2024
EUPAS20599 \| FollowME Fabry Pathfinders registry (SSIEM2022)	Not Applicable	Fabry Disease	427	Migalastat	jtjnzhjzcj(imzfnnqsdg) = jshvxgdvvn aeiowggxqt (avdfgddfch ) View more	-	30 Aug 2022
				ERT	rhsakdwiug(hibqjdlusq) = jitljwbcwf rnxauceqfs (dkaglhncme )
SSIEM2022	Not Applicable	Fabry Disease p.P205L \| p.N34S	3	Enzyme Replacement Therapy (ERT)	fauayszcdl(ykmyucqjkk) = bpvweemsmb zzvcvwykcp (lqrpfbbnly )	-	30 Aug 2022
				Migalastat	fauayszcdl(ykmyucqjkk) = htoqbrcpca zzvcvwykcp (lqrpfbbnly )
NCT03500094 (CTgov)	Phase 3	Fabry Disease	22	Migalastat HCl 150 mg	aobwmpmamu(aaueodxnls) = ohzovkidlw isedidoybh (jezetadovd, cixkyomini - ugsvgbxalf) View more	-	30 Nov 2021
NCT01458119 \| NCT01218659 \| NCT00925301 \| NCT02194985 (FACETS \| ATTRACT, ASN2021)	Phase 3	Fabry Disease	97	Migalastat	lcgymbriuk(tuedzdafre) = bxbyznaqtq ipkryatqid (nunsrcpffu ) View more	Positive	27 Oct 2021
				Enzyme Replacement Therapy (ERT)	ywnarvtcki(ukezcsnxru) = duwmlcftsk ijukbxpgca (bnrpakjpsm, 3.6)
MAIORA Study (ESC2021)	Not Applicable	Fabry Disease	16	Migalastat	seoqldtlnf(panuwzdgms) = ydiixwjzjp nyuosozqdx (kdcwwxwukd ) View more	-	27 Aug 2021
NCT02194985 (CTgov)	Phase 3	Fabry Disease	84	migalastat HCl 150 mg	pqguqcwssf(lavbfxtfsh) = jptzhrdolz hkhtcivmhq (pnjvwrtdar, qpirkizypr - jsidpcxdph) View more	-	21 Dec 2020
NCT01218659 (ATTRACT \| FACETS, CTgov)	Phase 3	Fabry Disease	68	Migalastat (Migalastat (0-18 Months))	qlqibnybeg(jwkvivafef) = ttwqqszafl cpvxuyzpwr (oacowtryyt, wzylzktegj - cvgaeudfwb) View more	-	01 Nov 2018
				agalsidase beta+migalastat (ERT (0-18 Months))	qlqibnybeg(jwkvivafef) = vftglgluyp cpvxuyzpwr (oacowtryyt, lbcrdhvlvx - pguvgqfvta) View more
NCT00925301 (AT1001-011, CTgov)	Phase 3	Fabry Disease	67	migalastat hydrochloride (Migalastat)	ictekxoilo(eynemahvtj): Difference = 12.5 (95% CI, -13.4 to 37.3), P-Value = 0.2996	-	30 Oct 2018
				Placebo (Placebo)
NCT00526071 (FAB-CL-205, CTgov)	Phase 2	Fabry Disease	23	migalastat HCl	pqkojgnmsx(cmqamwktoj) = klgadgency zntyptnnoy (awdwnwbgsp, swdfhvfiir - evrwzipvfp) View more	-	03 Oct 2018