DOCSLIB.ORG

GALAFOLD to Give a Minimum 4 Hours GALAFOLD Safely and Effectively

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
GALAFOLD to Give a Minimum 4 Hours GALAFOLD Safely and Effectively HIGHLIGHTS OF PRESCRIBING INFORMATION • Take on an empty stomach. Do not consume food at least 2 hours before These highlights do not include all the information needed to use and 2 hours after taking GALAFOLD to give a minimum 4 hours GALAFOLD safely and effectively. See full prescribing information for fast. (2) GALAFOLD. • Do not take GALAFOLD on 2 consecutive days. (2) • If a dose is missed entirely for the day, take the missed dose only if it is ™ GALAFOLD (migalastat) capsules, for oral use within 12 hours of the normal time that the dose should have been taken. Initial U.S. Approval: 2018 If more than 12 hours have passed, resume taking GALAFOLD at the next planned dosing day and time and according to the every-other-day -----------------------------INDICATIONS AND USAGE-------------------------­ dosing schedule. (2) GALAFOLD™ is an alpha-galactosidase A (alpha-Gal A) pharmacological • Swallow capsules whole; do not cut, crush, or chew. (2) chaperone indicated for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based ----------------------DOSAGE FORMS AND STRENGTHS--------------------­ on in vitro assay data. (1, 12.1) Capsules: 123 mg migalastat. (3) This indication is approved under accelerated approval based on reduction in --------------------------------CONTRAINDICATIONS----------------------------­ kidney interstitial capillary cell globotriaosylceramide (KIC GL-3) substrate. Continued approval for this indication may be contingent upon verification None. (4) and description of clinical benefit in confirmatory trials. (1) --------------------------------ADVERSE REACTIONS----------------------------­ ------------------------DOSAGE AND ADMINISTRATION---------------------­ Most common adverse drug reactions ≥ 10% are: headache, nasopharyngitis, urinary tract infection, nausea, and pyrexia. (6.1) • Select adults with confirmed Fabry disease who have an amenable GLA variant for treatment with GALAFOLD. To report SUSPECTED ADVERSE REACTIONS, contact Amicus • Treatment is indicated for patients with an amenable GLA variant that is Therapeutics at 1-877-4AMICUS or FDA at 1-800-FDA-1088 or interpreted by a clinical genetics professional as causing Fabry disease www.fda.gov/medwatch. (pathogenic, likely pathogenic) in the clinical context of the patient. Consultation with a clinical genetics professional is strongly See 17 for PATIENT COUNSELING INFORMATION and recommended in cases where the amenable GLA variant is of uncertain FDA-approved patient labeling. clinical significance (VUS, variant of uncertain significance) or may be benign (not causing Fabry disease). (2, 12.1) Revised: 08/2018 • The recommended dosage regimen of GALAFOLD is 123 mg orally once every other day at the same time of day. (2) FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 12 CLINICAL PHARMACOLOGY 2 DOSAGE AND ADMINISTRATION 12.1 Mechanism of Action 3 DOSAGE FORMS AND STRENGTHS 12.2 Pharmacodynamics 4 CONTRAINDICATIONS 12.3 Pharmacokinetics 6 ADVERSE REACTIONS 13 NONCLINICAL TOXICOLOGY 6.1 Clinical Trials Experience 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 8 USE IN SPECIFIC POPULATIONS 14 CLINICAL STUDIES 8.1 Pregnancy 16 HOW SUPPLIED/STORAGE AND HANDLING 8.2 Lactation 17 PATIENT COUNSELING INFORMATION 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use * Sections or subsections omitted from the full prescribing information are not 8.5 Geriatric Use listed. 8.6 Renal Impairment 11 DESCRIPTION 1 Reference ID: 4305282 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE ™ GALAFOLD is indicated for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data [see Clinical Pharmacology (12.1)]. This indication is approved under accelerated approval based on reduction in kidney interstitial capillary cell globotriaosylceramide (KIC GL-3) substrate [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 2 DOSAGE AND ADMINISTRATION • Select adults with confirmed Fabry disease who have an amenable GLA variant for treatment with GALAFOLD [see Table 2 in Clinical Pharmacology (12.1)]. • Treatment is indicated for patients with an amenable GLA variant that is interpreted by a clinical genetics professional as causing Fabry disease (pathogenic, likely pathogenic) in the clinical context of the patient. Consultation with a clinical genetics professional is strongly recommended in cases where the amenable GLA variant is of uncertain clinical significance (VUS, variant of uncertain significance) or may be benign (not causing Fabry disease). • The recommended dosage regimen of GALAFOLD is 123 mg orally once every other day at the same time of day. • Take GALAFOLD on an empty stomach. Do not consume food at least 2 hours before and 2 hours after taking GALAFOLD to give a minimum 4 hours fast [see Clinical Pharmacology (12.3)]. Clear liquids can be consumed during this 4-hour period. • Do not take GALAFOLD on 2 consecutive days. • If a dose is missed entirely for the day, take the missed dose of GALAFOLD only if it is within 12 hours of the normal time that the dose should have been taken. If more than 12 hours have passed, resume taking GALAFOLD at the next planned dosing day and time, according to the every-other-day dosing schedule. • Swallow capsules whole. Do not cut, crush, or chew. 3 DOSAGE FORMS AND STRENGTHS Capsules: 123 mg of migalastat in a size “2” capsule with an opaque blue cap and opaque white body with “A1001” printed in black, containing white to pale brown powder. 2 Reference ID: 4305282 4 CONTRAINDICATIONS None. 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, 139 patients with Fabry disease (79 females, 60 males, 92% Caucasian, ages 16 to 72 years), who were naïve to GALAFOLD or previously treated with enzyme replacement therapy, were exposed to at least one dose of GALAFOLD. Of the 139 patients, 127 patients were exposed to GALAFOLD 123 mg every other day for 6 months and 123 patients were exposed for greater than one year. The clinical trials included one randomized, double-blind, placebo-controlled clinical trial of 6 months duration followed by a 6-month open-label treatment phase (Study 1) [see Clinical Studies (14)]. A second trial was a randomized, open-label, active-controlled clinical trial of 18 months duration in patients with Fabry disease receiving enzyme replacement therapy who were randomized to either switch to GALAFOLD or continue enzyme replacement therapy (Study 2; NCT01218659). In addition, there were two open-label, long-term extension trials. The most common adverse reactions reported with GALAFOLD (≥ 10%) during the 6-month placebo-controlled, double-blind phase of Study 1 were headache, nasopharyngitis, urinary tract infection, nausea, and pyrexia. Table 1 shows adverse reactions reported in at least 5% of patients treated with GALAFOLD (and at a higher rate than placebo) during the 6-month placebo-controlled, double-blind phase of Study 1. 3 Reference ID: 4305282 Table 1: Adverse Reactions* Reported During the First 6 Months of Treatment in Patients with Fabry Disease in Study 1 Adverse Reaction GALAFOLD Placebo % % (N = 34) (N = 33) Headache 35% 21% Nasopharyngitis 18% 6% Urinary tract infection** 15% 0 Nausea 12% 6% Pyrexia 12% 3% Abdominal pain 9% 3% Back pain 9% 0 Cough 9% 0 Diarrhea 9% 3% Epistaxis 9% 3% * reported in at least 5% of patients treated with GALAFOLD and at a higher rate than placebo ** included urinary tract infection, cystitis, and kidney infection Adverse reactions reported in > 5% of patients who received migalastat in the 6-month open-label treatment phase of Study 1, in Study 2, and in the long-term extension trials (N = 115, mean duration of treatment 2.7 years) included those reported in Table 1 with the addition of vomiting. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There were three pregnant women with Fabry disease exposed to GALAFOLD in clinical trials. As such, the available data are not sufficient to assess drug associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed (see Data). The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 4 Reference ID: 4305282 Data Animal Data No adverse developmental effects were observed with oral administration of migalastat to pregnant rats and rabbits during organogenesis at doses up to 26 and 54 times, respectively, the recommended dose based on AUC. No effects on post-natal development were observed following oral administration of up to 500 mg/kg migalastat twice daily to pregnant rats (16 times the recommended dose based on AUC) during organogenesis and through lactation. 8.2 Lactation Risk Summary There are no
Load more

Recommended publications
  • CDR Clinical Review Report for Galafold
    CADTH COMMON DRUG REVIEW Clinical Review Report MIGALASTAT (GALAFOLD) (Amicus Therapeutics) Indication: Fabry Disease Service Line: CADTH Common Drug Review Version: Final Publication Date: February 2018 Report Length: 98 Pages Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH.
    [Show full text]
  • Galafold, INN-Migalastat Hydrochloride
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Galafold 123 mg hard capsules 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each capsule contains migalastat hydrochloride equivalent to 123 mg migalastat. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Hard capsule. Size 2 hard capsule (6.4x18.0 mm) with an opaque blue cap and opaque white body with “A1001” printed in black containing white to pale brown powder. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Galafold is indicated for long-term treatment of adults and adolescents aged 16 years and older with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) and who have an amenable mutation (see the tables in section 5.1). 4.2 Posology and method of administration Treatment with Galafold should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of Fabry disease. Galafold is not intended for concomitant use with enzyme replacement therapy (see section 4.4). Posology The recommended dosage regimen in adults and adolescents 16 years and older is 123 mg migalastat (1 capsule) once every other day at the same time of day. Missed dose Galafold should not be taken on 2 consecutive days. If a dose is missed entirely for the day, patients should resume taking Galafold at the next dosing day and time.
    [Show full text]
  • An Open-Label Study of the Safety, Pharmacokinetics
    CLINICAL STUDY PROTOCOL AN OPEN-LABEL STUDY OF THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF 12-MONTH TREATMENT WITH MIGALASTAT IN PEDIATRIC SUBJECTS (AGED 12 TO < 18 YEARS) WITH FABRY DISEASE AND AMENABLE GLA VARIANTS Protocol Number: AT1001-020 Version 5: Amendment 4 Protocol Date: 13 June 2019 Original Protocol: 20 February 2018 Amendment 1 Protocol: 10 September 2018 Amendment 2 Protocol: 31 October 2018 Amendment 3 Protocol: 22 April 2019 (UK-specific) EudraCT No.: 2017-000146-21 US IND Number: 068456 Compound: Migalastat Sponsor Amicus Therapeutics UK Limited One Globeside, Fieldhouse Lane, Marlow Buckinghamshire SL7 1HZ United Kingdom The information in this document is the property of Amicus Therapeutics and is strictly confidential. Neither the document nor the information contained herein may be reproduced or disclosed outside of Amicus Therapeutics without the prior written consent of the company, except to the extent required under applicable laws or regulations. Amicus Therapeutics Protocol AT1001-020 Amendment 4 Table 1: Serious Adverse Event Reporting and Medical Monitor Contact Information Role Name/Address Contact Information Safety Physician Amicus Tel: +1 609-366-1164 (Questions Regarding Amicus Therapeutics, Inc. Email: Amicus SAE Reporting) 1 Cedar Brook Drive Cranbury, NJ 08512 USA SAE Reporting Primary method: Safety FAX number: +1 866-422-1278 If the primary method fails, please use: Safety Email address: [email protected] Contract Medical Monitor Amicus Tel: +1 919-745-2723 Syneos Health Email: 3201 Beechleaf Court, Suite 600 Amicus Raleigh, NC 27604 USA Sponsor Medical Monitor Amicus Tel: +1 609-662-2033 Amicus Therapeutics, Inc. Email: Amicus 1 Cedar Brook Drive Cranbury, NJ 08512 USA Abbreviation: SAE = serious adverse event 13 June 2019 Page 2 of 70 Confidential Amicus Therapeutics Protocol AT 1001-020 Amendment4 1.
    [Show full text]
  • WO 2019/020362 Al 31 January 2019 (31.01.2019) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2019/020362 Al 31 January 2019 (31.01.2019) W !P O PCT (51) International Patent Classification: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, C07D 211/42 (2006.01) C07D 211/02 (2006.01) SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (21) International Application Number: PCT/EP20 18/068648 (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (22) International Filing Date: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, 10 July 2018 (10.07.2018) UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (25) Filing Language: English TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (26) Publication Language: English MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (30) Priority Data: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 102017000078102 11 July 2017 ( 11.07.2017) IT KM, ML, MR, NE, SN, TD, TG). (71) Applicant: DIPHARMA FRANCIS S.R.L. [IT/IT]; Via Published: Bissone, 5, 20021 Baranzate (MI) (IT). — with international search report (Art. 21(3)) (72) Inventors: ATTOLINO, Emanuele; c/o Dipharma Fran — before the expiration of the time limit for amending the cis S.r.L, Via Bissone, 5, 20021 Baranzate (MI) (IT).
    [Show full text]
  • Amicus Therapeutics Announces First Quarter 2010 Financial Results and Product Pipeline Advancements
    Amicus Therapeutics Announces First Quarter 2010 Financial Results and Product Pipeline Advancements Recent Positive Phase 2 Extension study data for Amigal(TM) support confidence in Phase 3 program in Fabry; Focus on completing enrollment for Phase 3 U.S. Registration by year end; Preliminary Phase 3 results expected mid-2011 CRANBURY, N.J., May 6, 2010 /PRNewswire via COMTEX News Network/ -- Amicus Therapeutics (Nasdaq: FOLD) today announced financial results for the quarter ended March 31, 2010 and reviewed the progress on its product development pipeline including an update that the Company does not plan to advance AT2220, its investigational drug AT2220 (1- deoxynojirimycin HCl) for the treatment of Pompe disease, as a monotherapy at this time. First Quarter Highlights: ● Amicus presented positive data from its Phase 2 extension study of Amigal(TM) (migalastat HCl) for Fabry disease and encouraging preclinical data relating to its programs in Parkinson's disease and the combination use of chaperones and enzyme replacement therapies; ● The Company completed an $18.5 million Registered Direct Offering of common stock, (net proceeds of approximately $17.1 million) further strengthening its financial position; ● The Alzheimer's Drug Discovery Foundation (ADDF) provided Amicus a grant for preclinical research on the use of pharmacological chaperones in the treatment of Alzheimer's disease; and ● Amicus' Board of Directors named the Company's Chief Executive Officer, John F. Crowley, Chairman of the Board, and Donald J. Hayden, Jr., Lead Independent Director. John F. Crowley, Chairman and CEO of Amicus Therapeutics stated, "We began 2010 with positive momentum and are very pleased with our progress throughout the first quarter.
    [Show full text]
  • CENTER for DRUG EVALUATION and RESEARCH Approval
    CENTER FOR DRUG EVALUATION AND RESEARCH Approval Package for: APPLICATION NUMBER: 208623Orig1s000 Trade Name: Galafold capsules, 123 mg. Generic or migalastat Established: Sponsor: Amicus Therapeutics U.S., Inc. Approval Date: August 10, 2018 Indication: For the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data. CENTER FOR DRUG EVALUATION AND RESEARCH 208623Orig1s000 CONTENTS Reviews / Information Included in this NDA Review. Approval Letter X Other Action Letters Labeling X REMS Officer/Employee List X Multidiscipline Review(s) X Summary Review Office Director Cross Discipline Team Leader Clinical Non-Clinical Statistical Clinical Pharmacology Product Quality Review(s) X Clinical Microbiology / Virology Review(s) Other Reviews X Risk Assessment and Risk Mitigation Review(s) X Proprietary Name Review(s) X Administrative/Correspondence Document(s) X CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 208623Orig1s000 APPROVAL LETTER DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 208623 NDA APPROVAL Amicus Therapeutics U.S., Inc. Attention: Vivian Kessler, RAC Executive Director, Global Regulatory Affairs 1 Cedarbrook Drive Cranbury, New Jersey 08512 Dear Ms. Kessler: Please refer to your New Drug Application (NDA) dated and received December 13, 2017, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Galafold (migalastat) capsules, 123 mg. We also refer to our approval letter dated August 10, 2018, which contained the following error: 150 mg as the strength. The corrected strength is 123 mg. This replacement approval letter incorporates the correction of the error.
    [Show full text]
  • LONG-TERM SAFETY of MIGALASTAT Hcl in PATIENTS with FABRY DISEASE D.P
    LONG-TERM SAFETY OF MIGALASTAT HCl IN PATIENTS WITH FABRY DISEASE D.P. Germain1, R. Giugliani2, G.M. Pastores3, K. Nicholls4, S. Shankar5, R. Schiffmann6, D. Hughes7, A.B. Mehta7, S. Waldek8, A. Jovanovic8, J.K. Simosky9, P. Boudes9 1. University of Versailles (UVSQ), Division of Medical Genetics, Garches, France; 2. Med Genet Serv/HCPA, Dep Genetics/UFRGS and INAGEMP, Porto Alegre, RS, Brazil; 3. New York University, New York, NY, 4. Royal Melbourne Hospital and University of Melbourne, Parkville, Australia; 5. Emory University, Atlanta, GA, 6. Baylor Research Institute, Dallas, TX, 7. Royal Free Hospital, London, UK; 8. Salford Royal Hospital, Manchester, UK (Waldek retired Oct 2011, now an Independent Medical Consultant), 9. Amicus Therapeutics, Cranbury, NJ, USA BACKGROUND STUDY SCHEMATIC, EXPOSURE, & PATIENT DISPOSITION Fabry disease (FD) results from an inborn X-linked error of glycosphingolipid metabolism in which deficiency of α-galactosidase A (α-Gal A) leads to accumulation of globotriaosylceramide (GL-3). Accumulation of GL-3 in the vascular endothelium and visceral tissues throughout the body leads to multiorgan dysfunction, including progressive kidney or heart disease, and/or stroke. Migalastat HCl (AT1001/GR181413A) is an oral investigational pharmacologic chaperone that binds and stabilizes α-Gal A. Specific mutant forms of α-Gal A have been identified as amenable to migalastat HCl with a cell- based assay. Migalastat HCl is currently in Phase 3 development for Fabry disease in patients with α-Gal A mutations amenable to treatment. Within FAB-CL-205, the overall median duration of exposure to migalastat HCl was Study FAB-CL-205 (NCT00526071/MGM116045) is an 3.64 years (range 1.0 to 4.3 years) and reflects 75 patient-years of treatment.
    [Show full text]
  • Attachment: Extract from Clinical Evaluation: Migalastat
    AusPAR Attachment 2 Extract from the Clinical Evaluation Report for migalastat Proprietary Product Name: Galafold Sponsor: Amicus Therapeutics Pty Ltd First round: September 2016 Second round: February 2017 Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) · The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health, and is responsible for regulating medicines and medical devices. · The TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance), when necessary. · The work of the TGA is based on applying scientific and clinical expertise to decision- making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. · The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. · To report a problem with a medicine or medical device, please see the information on the TGA website <https://www.tga.gov.au>. About the Extract from the Clinical Evaluation Report · This document provides a more detailed evaluation of the clinical findings, extracted from the Clinical Evaluation Report (CER) prepared by the TGA. This extract does not include sections from the CER regarding product documentation or post market activities. · The words [Information redacted], where they appear in this document, indicate that confidential information has been deleted. · For the most recent Product Information (PI), please refer to the TGA website <https://www.tga.gov.au/product-information-pi>.
    [Show full text]
  • Migalastat for Fabry Disease in Children Aged 12 to 15 Years
    HEALTH TECHNOLOGY BRIEFING OCTOBER 2019 Migalastat for Fabry disease in children aged 12 to 15 years NIHRIO ID 24194 NICE ID 10134 Developer/Company Amicus UKPS ID 654113 Therapeutics UK Ltd Licensing and Currently in phase III clinical trial. market availability plans SUMMARY Migalastat is in clinical development for the treatment of Fabry disease for children aged 12 to 15 years old. Fabry disease is a rare genetic disorder caused by a defective gene (the GLA gene) in the body. In most cases, the defect in the gene causes a deficient quantity of the enzyme alpha-galactosidase A. This enzyme is necessary for the daily breakdown (metabolism) of a lipid (fatty substance) in the body called globotriaosylceramide abbreviated GL-3. When the proper metabolism of this lipids does not occur, GL-3 accumulates and leads to cell damage. The cell damage causes a wide range of symptoms including potentially life-threatening consequences such as kidney failure, heart attacks and strokes often at a relatively early age. Migalastat works by stabilizing the body's own dysfunctional enzyme, so it can clear the accumulated disease substrate in patients who have amenable mutations. Migalastat is currently licenced for patients aged 16 or over with Fabry disease and an amenable mutation. If the license is extended, migalastat may offer an additional treatment option for paediatric subjects 12 to 15 years old with Fabry disease and an amenable mutation, who weight over 45Kgs. This briefing reflects the evidence available at the time of writing and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes or commissioning without additional information.
    [Show full text]
  • Iminosugars: Effects of Stereochemistry, Ring
    pharmaceuticals Article Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities Luís O. B. Zamoner, Valquiria Aragão-Leoneti and Ivone Carvalho * School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Monte Alegre, CEP14040-903 Ribeirão Preto, Brazil * Correspondence: [email protected]; Tel.: +55-16-33154709 Received: 15 June 2019; Accepted: 10 July 2019; Published: 12 July 2019 Abstract: N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus. Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs. Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides. The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
    [Show full text]
  • GALAFOLD™ (Migalastat) Oral
    PHARMACY COVERAGE GUIDELINES ORIGINAL EFFECTIVE DATE: 9/20/2018 SECTION: DRUGS LAST REVIEW DATE: 8/19/2021 LAST CRITERIA REVISION DATE: 8/19/2021 ARCHIVE DATE: GALAFOLD™ (migalastat) oral Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Pharmacy Coverage Guideline must be read in its entirety to determine coverage eligibility, if any. This Pharmacy Coverage Guideline provides information related to coverage determinations only and does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the member are responsible for all decisions regarding the appropriateness of care. Providers should provide BCBSAZ complete medical rationale when requesting any exceptions to these guidelines. The section identified as “Description” defines or describes a service, procedure, medical device or drug and is in no way intended as a statement of medical necessity and/or coverage. The section identified as “Criteria” defines criteria to determine whether a service, procedure, medical device or drug is considered medically necessary or experimental or investigational. State or federal mandates, e.g., FEP program, may dictate that any drug, device or biological product approved by the U.S. Food and Drug Administration (FDA) may not be considered experimental or investigational and thus the drug, device or biological product may be assessed only on the basis of medical necessity. Pharmacy Coverage Guidelines are subject to change as new information becomes available. For purposes of this Pharmacy Coverage Guideline, the terms "experimental" and "investigational" are considered to be interchangeable. BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered service marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans.
    [Show full text]
  • An Amorphous and a Crystalline Form of Genz
    (19) TZZ Z¥¥ _T (11) EP 2 504 332 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 405/06 (2006.01) A61K 31/4025 (2006.01) 04.06.2014 Bulletin 2014/23 A61P 35/00 (2006.01) (21) Application number: 10785289.9 (86) International application number: PCT/US2010/057952 (22) Date of filing: 24.11.2010 (87) International publication number: WO 2011/066352 (03.06.2011 Gazette 2011/22) (54) AN AMORPHOUS AND A CRYSTALLINE FORM OF GENZ 112638 HEMITART RATE AS INHIBITOR OF GLUCOSYLCERAMIDE SYNTHASE EINE AMORPHE UND EINE KRISTALLINE FORM VON GENZ 112638 HEMITARTRATE ALS INHIBITOR DER GLUCOSYLCERAMID SYNTHASE UNE FORME AMORPHE ET UNE FORME CRYSTALLINE DU GENZ 112638 HÉMITARTRATE EN TANT QUE INHIBITEUR DE LA SYNTHASE GLUCOSYLCÉRAMIDE (84) Designated Contracting States: • MARSHALL, John AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Hopedale, MA 01747 (US) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • KOCHLING, Jianmei PL PT RO RS SE SI SK SM TR Wellesley, MA 02482 (US) Designated Extension States: •PALACE,Gerard BA ME Framingham, MA 01701 (US) • PETERSCHMITT, Judith (30) Priority: 27.11.2009 US 264748 P Watertown, MA 02472 (US) •SIEGEL,Craig (43) Date of publication of application: Woburn, MA 01801 (US) 03.10.2012 Bulletin 2012/40 • CHENG, Seng Natick, MA 01760 (US) (60) Divisional application: 14164650.5 (74) Representative: Potter Clarkson LLP The Belgrave Centre (73) Proprietor: Genzyme Corporation Talbot Street Cambridge, MA 02142 (US) Nottingham, NG1 5GG (GB) (72) Inventors: (56) References cited: •LIU,Hanlan WO-A2-2006/053043 Lexington, MA 02420 (US) • WILLIS, Chris • MCEACHERN, KERRY ANNE ET AL: "A specific Southborough, MA 01772 (US) and potent inhibitor of glucosylceramide • BHARDWAJ, Renu synthase for substrate inhibition therapy of Ashland, MA 01721 (US) Gaucherdisease", MOLECULAR GENETICSAND • COPELAND, Diane, P.
    [Show full text]