DOCSLIB.ORG

For Peer Review Only - Page 1 of 59 BMJ Open

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
For Peer Review Only - Page 1 of 59 BMJ Open BMJ Open BMJ Open: first published as 10.1136/bmjopen-2014-007199 on 24 June 2015. Downloaded from BMJ Open: first published as 10.1136/bmjopen-2014-007199 on 24 June 2015. Downloaded from The effectiveness, safety and costs of orphan drugs: an evidence-based review ForJournal: peerBMJ Open review only Manuscript ID: bmjopen-2014-007199 Article Type: Research Date Submitted by the Author: 14-Nov-2014 Complete List of Authors: Onakpoya, Igho; University of Oxford, Primary Care Health Sciences Spencer, Elizabeth; University of Oxford, Primary Care Health Sciences Thompson, Matthew; Oxford University, Department of Primary Care Health Sciences Heneghan, Carl; Oxford University, Primary Health Care <b>Primary Subject Evidence based practice Heading</b>: Evidence based practice, Pharmacology and therapeutics, General practice Secondary Subject Heading: / Family practice GENERAL MEDICINE (see Internal Medicine), PRIMARY CARE, ORPHAN Keywords: DRUGS http://bmjopen.bmj.com/ http://bmjopen.bmj.com/ on September 28, 2021 by guest. Protected copyright. on September 28, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 59 BMJ Open 1 BMJ Open: first published as 10.1136/bmjopen-2014-007199 on 24 June 2015. Downloaded from 1 2 3 The effectiveness, safety and costs of orphan drugs: an evidence-based review 4 5 6 7 Igho J. Onakpoya 8 9 10 University of Oxford, Centre for Evidence-Based Medicine, Nuffield Department of Primary 11 12 Care Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Oxford, United 13 14 Kingdom OX2 6GG 15 For peer review only 16 17 18 19 Elizabeth A. Spencer 20 21 University of Oxford, Centre for Evidence-Based Medicine, Nuffield Department of Primary 22 23 Care Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Oxford, United 24 25 Kingdom OX2 6GG 26 27 28 29 30 Matthew J. Thompson 31 32 Department of Family Medicine, University of Washington, Seattle, USA WA 98195-6390 33 http://bmjopen.bmj.com/ 34 35 36 Carl J. Heneghan 37 38 39 University of Oxford, Centre for Evidence-Based Medicine, Nuffield Department of Primary 40 41 Care Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Oxford, United on September 28, 2021 by guest. Protected copyright. 42 43 Kingdom OX2 6GG 44 45 46 47 Corresponding author: Igho Onakpoya, University of Oxford, Nuffield Department of Primary Care 48 49 Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Oxford, United Kingdom 50 51 OX2 6GG. Email: [email protected]. Tel: +44 (0)1865 289672 52 53 54 55 56 Keywords: orphan drugs; cost; prevalence; effectiveness; safety; review 57 58 Word count: 4,340 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 59 2 BMJ Open: first published as 10.1136/bmjopen-2014-007199 on 24 June 2015. Downloaded from 1 2 3 ABSTRACT 4 5 Introduction: Several orphan drugs have been approved by the European Medicines Agency 6 7 (EMA) over the past two decades. However, the prices of the drugs are expensive, and in 8 9 10 some instances, the evidence for effectiveness is not convincing at the time of regulatory 11 12 approval. Our objective was to evaluate the clinical effectiveness of orphan drugs which have 13 14 been granted marketing licenses in Europe, determine the annual costs of each drug, compare 15 For peer review only 16 the costs of branded orphan drugs against their generic equivalents, and explore any 17 18 19 relationships between orphan disease prevalence and annual costs. 20 21 Methods: We searched the EMA database to identify orphan drugs granted marketing 22 23 authorization up till April, 2014. Electronic searches were also conducted in Pubmed, 24 25 Embase, and Google Scholar to assess data on effectiveness, safety and annual costs. Two 26 27 reviewers independently evaluated the levels and quality of evidence and extracted data. 28 29 30 Results: We identified 74 orphan drugs, with 54 (73%) demonstrating moderate quality of 31 32 evidence. 85% showed significant clinical effects, but serious adverse events were reported in 33 http://bmjopen.bmj.com/ 34 86.5%. Their annual costs were between £726 and £378,000. There was a significant 35 36 relationship between disease prevalence and annual costs (p = 0.01); this was largely due to 37 38 39 the influence of the ultra-orphan diseases. We could not determine whether the balance 40 41 between effectiveness and safety influenced annual costs. For 10 drugs where generic on September 28, 2021 by guest. Protected copyright. 42 43 alternatives were available, the branded drugs were 1.4 to 82,000 times more expensive. 44 45 Conclusion: The available evidence suggests that there is inconsistency in the quality of 46 47 evidence of approved orphan drugs, and there is no clear mechanism for determining their 48 49 50 prices. In some cases far cheaper generic agents appear to be available. A more robust, 51 52 transparent and standard mechanism for determining annual costs is imperative. 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 59 BMJ Open 3 BMJ Open: first published as 10.1136/bmjopen-2014-007199 on 24 June 2015. Downloaded from 1 2 3 Strengths and limitations 4 5 • We employed a robust strategy to search for the best quality evidence for effectiveness 6 7 8 • We used standardized methods to rate the quality and level of evidence for each orphan 9 10 drug 11 12 • We also used reliable data to document the prevalence of each orphan disease and identify 13 14 the annual cost of each orphan drug 15 For peer review only 16 17 • Because we could not document the R and D costs associated with the approval of each 18 19 orphan drug, the influence of this variable on their annual costs could not be ascertained 20 21 • The inconsistencies in the quality of evidence for some orphan drugs limits the 22 23 conclusions that could be drawn regarding their effectiveness and safety 24 25 26 27 28 29 30 31 32 33 http://bmjopen.bmj.com/ 34 35 36 37 38 39 40 41 on September 28, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 59 4 BMJ Open: first published as 10.1136/bmjopen-2014-007199 on 24 June 2015. Downloaded from 1 2 3 INTRODUCTION 4 5 Orphan drugs are therapeutic agents designed for the management of orphan diseases,1 which 6 7 are defined as medical conditions with a low prevalence. In the United States (US), orphan 8 9 2 10 diseases are defined as those affecting approximately 1 in 1,500 persons [ ], while in Europe 11 2,3 12 it is 1 in 2,000. In Europe, ultra-orphan designations are used to specify rare diseases with 13 14 prevalence less than 1 in 50,000.2,4 15 For peer review only 16 17 18 19 Because low patient volumes make it unfavourable for commercial investment in orphan drug 20 21 research, drug regulatory authorities have incentives in place to encourage their development 22 23 and manufacture by pharmaceutical companies. In the US, these include exclusive licencing 24 25 to market such drugs for seven years, faster assessment procedures, and tax incentives.1 In 26 27 Europe, incentives include exclusive licensing for 10 years, reduction in the fees paid for 28 29 1,5 30 regulatory activities, and (provision of scientific advice by drug regulatory bodies. Despite 31 32 these incentives, the costs of orphan drugs are still high, especially when generic versions of 33 http://bmjopen.bmj.com/ 34 the same agent are available.6 In the United Kingdom for example, some funders of care 35 36 under the National Health Service have refused to fund the orphan drugs because they are not 37 38 7 39 considered cost effective. Factors which reportedly influence their price setting include 40 41 research and development (R & D) costs, clinical effectiveness, drug quality, and disease on September 28, 2021 by guest. Protected copyright. 42 43 prevalence.8,9 However, the effectiveness of some orphan drugs has not been clearly 44 45 demonstrated, and the evidence regarding their safety is often sparse at the time of regulatory 46 47 approval.10 48 49 50 51 52 A previous systematic review of 11 orphan drugs approved in the Netherlands concluded that 53 54 there is scarcity of information on the cost effectiveness of the drugs.11 A more recent 55 56 systematic review of orphan drug legislation in Europe also advocated for more stringent 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 59 BMJ Open 5 BMJ Open: first published as 10.1136/bmjopen-2014-007199 on 24 June 2015. Downloaded from 1 2 3 approval criteria for evaluating the clinical and cost effectiveness of orphan drugs.12 Another 4 5 systematic review of orphan drugs used in cancers showed that they have varying levels in 6 7 quality of evidence and dearth of information on economic value.13 While the first two 8 9 10 reviews did not evaluate the quality of the evidence, the third review focussed only on drugs 11 12 marketed in the US. 13 14 15 For peer review only 16 The objective of this review was to evaluate the effectiveness and safety of all orphan drugs 17 18 19 which have been granted marketing licenses in Europe, determine the annual costs of each 20 21 drug, compare the costs of branded orphan drugs against their generic equivalents, and 22 23 explore the relationship between orphan disease prevalence and annual costs.
Load more

Recommended publications
  • Intravenous Enzyme Replacement Therapy (ERT) for Gaucher Disease
    UnitedHealthcare® Commercial Medical Benefit Drug Policy Intravenous Enzyme Replacement Therapy (ERT) for Gaucher Disease Policy Number: 2021D0048K Effective Date: April 1, 2021 Instructions for Use Table of Contents Page Related Commercial Policy Coverage Rationale ....................................................................... 1 • Provider Administered Drugs – Site of Care Applicable Codes .......................................................................... 3 Background.................................................................................... 3 Community Plan Policy Benefit Considerations .................................................................. 3 • Intravenous Enzyme Replacement Therapy (ERT) Clinical Evidence ........................................................................... 4 for Gaucher Disease U.S. Food and Drug Administration ............................................. 6 Centers for Medicare and Medicaid Services ............................. 6 References ..................................................................................... 7 Policy History/Revision Information ............................................. 8 Instructions for Use ....................................................................... 8 Coverage Rationale See Benefit Considerations This policy refers to the following drug products, all of which are intravenous enzyme replacement therapies used in the treatment of Gaucher disease: Cerezyme® (imiglucerase) Elelyso® (taliglucerase) VPRIV® (velaglucerase)
    [Show full text]
  • Ten Years of the Hunter Outcome Survey (HOS): Insights, Achievements, and Lessons Learned from a Global Patient Registry Joseph Muenzer1, Simon A
    Muenzer et al. Orphanet Journal of Rare Diseases (2017) 12:82 DOI 10.1186/s13023-017-0635-z REVIEW Open Access Ten years of the Hunter Outcome Survey (HOS): insights, achievements, and lessons learned from a global patient registry Joseph Muenzer1, Simon A. Jones2, Anna Tylki-Szymańska3, Paul Harmatz4, Nancy J. Mendelsohn5,6, Nathalie Guffon7, Roberto Giugliani8, Barbara K. Burton9, Maurizio Scarpa10,11, Michael Beck12, Yvonne Jangelind13, Elizabeth Hernberg-Stahl14, Maria Paabøl Larsen15,17, Tom Pulles16,18 and David A. H. Whiteman15* Abstract Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM 309900) is a rare lysosomal storage disease with progressive multisystem manifestations caused by deficient activity of the enzyme iduronate-2-sulfatase. Disease- specific treatment is available in the form of enzyme replacement therapy with intravenous idursulfase (Elaprase®, Shire). Since 2005, the Hunter Outcome Survey (HOS) has collected real-world, long-term data on the safety and effectiveness of this therapy, as well as the natural history of MPS II. Individuals with a confirmed diagnosis of MPS II who are untreated or who are receiving/have received treatment with idursulfase or bone marrow transplant can be enrolled in HOS. A broad range of disease- and treatment-related information is captured in the registry and, over the past decade, data from more than 1000 patients from 124 clinics in 29 countries have been collected. Evidence generated from HOS has helped to improve our understanding of disease progression in both treated and untreated patients and has extended findings from the formal clinical trials of idursulfase. As a long-term, global, observational registry, various challenges relating to data collection, entry, and analysis have been encountered.
    [Show full text]
  • Publications in Scientific Journals (Peer Reviewed) 1
    Last Updated July 2020 Publications in Scientific Journals (Peer Reviewed) 1. Eisengart JB, King KE, Shapiro EG, Whitley CB, Muenzer J. The nature and impact of neurobehavioral symptoms in neuronopathic Hunter syndrome. Mol Genet Metab Rep. 2019 Dec 20;22:100549. PMID: 32055445 2. Viskochil D, Clarke LA, Bay L, Keenan H, Muenzer J, Guffon N. Growth patterns for untreated individuals with MPS I: Report from the international MPS I registry. Am J Med Genet A. 2019 Dec;179(12):2425-2432. PMID: 31639289 3. Clarke LA, Giugliani R, Guffon N, Jones SA, Keenan HA, Munoz-Rojas MV, Okuyama T, Viskochil D, Whitley CB, Wijburg FA, Muenzer J. Genotype-phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry. Clin Genet. 2019 Clin Genet. 2019 Oct;96(4):281-289. PMID: 31194252 4. Taylor JL, Clinard K, Powell CM, Rehder C, Young SP, Bali D, Beckloff SE, Gehtland LM, Kemper AR, Lee S, Millington D, Patel HS, Shone SM, Woodell C, Zimmerman SJ, Bailey DB Jr, Muenzer J. The North Carolina Experience with Mucopolysaccharidosis Type I Newborn Screening. J Pediatr. 2019 Aug;211:193-200. PMID: 31133280 5. Akyol MU, Alden TD, Amartino H, Ashworth J, Belani K, Berger KI, Borgo A, Braunlin E, Eto Y, Gold JI, Jester A, Jones SA, Karsli C, Mackenzie W, Marinho DR, McFadyen A, McGill J, Mitchell JJ, Muenzer J, Okuyama T, Orchard PJ, Stevens B, Thomas S, Walker R, Wynn R, Giugliani R, Harmatz P, Hendriksz C, Scarpa M; MPS Consensus Programme Steering Committee; MPS Consensus Programme Co-Chairs.
    [Show full text]
  • WHO Drug Information Vol 22, No
    WHO Drug Information Vol 22, No. 1, 2008 World Health Organization WHO Drug Information Contents Challenges in Biotherapeutics Miglustat: withdrawal by manufacturer 21 Regulatory pathways for biosimilar Voluntary withdrawal of clobutinol cough products 3 syrup 22 Pharmacovigilance Focus Current Topics WHO Programme for International Drug Proposed harmonized requirements: Monitoring: annual meeting 6 licensing vaccines in the Americas 23 Sixteen types of counterfeit artesunate Safety and Efficacy Issues circulating in South-east Asia 24 Eastern Mediterranean Ministers tackle Recall of heparin products extended 10 high medicines prices 24 Contaminated heparin products recalled 10 DacartTM development terminated and LapdapTM recalled 11 ATC/DDD Classification Varenicline and suicide attempts 11 ATC/DDD Classification (temporary) 26 Norelgestromin-ethynil estradiol: infarction ATC/DDD Classification (final) 28 and thromboembolism 12 Emerging cardiovascular concerns with Consultation Document rosiglitazone 12 Disclosure of transdermal patches 13 International Pharmacopoeia Statement on safety of HPV vaccine 13 Cycloserine 30 IVIG: myocardial infarction, stroke and Cycloserine capsules 33 thrombosis 14 Erythropoietins: lower haemoglobin levels 15 Recent Publications, Erythropoietin-stimulating agents 15 Pregabalin: hypersensitivity reactions 16 Information and Events Cefepime: increased mortality? 16 Assessing the quality of herbal medicines: Mycophenolic acid: pregnancy loss and contaminants and residues 36 congenital malformation 17 Launch
    [Show full text]
  • Enzyme Replacement Therapy Srx-0019 Policy Type ☒ Medical ☐ Administrative ☐ Payment
    MEDICAL POLICY STATEMENT Original Effective Date Next Annual Review Date Last Review / Revision Date 06/15/2011 03/15/2017 10/04/2016 Policy Name Policy Number Enzyme Replacement Therapy SRx-0019 Policy Type ☒ Medical ☐ Administrative ☐ Payment Medical Policy Statements prepared by CSMG Co. and its affiliates (including CareSource) are derived from literature based on and supported by clinical guidelines, nationally recognized utilization and technology assessment guidelines, other medical management industry standards, and published MCO clinical policy guidelines. Medically necessary services include, but are not limited to, those health care services or supplies that are proper and necessary for the diagnosis or treatment of disease, illness, or injury and without which the patient can be expected to suffer prolonged, increased or new morbidity, impairment of function, dysfunction of a body organ or part, or significant pain and discomfort. These services meet the standards of good medical practice in the local area, are the lowest cost alternative, and are not provided mainly for the convenience of the member or provider. Medically necessary services also include those services defined in any Evidence of Coverage documents, Medical Policy Statements, Provider Manuals, Member Handbooks, and/or other policies and procedures. Medical Policy Statements prepared by CSMG Co. and its affiliates (including CareSource) do not ensure an authorization or payment of services. Please refer to the plan contract (often referred to as the Evidence of Coverage) for the service(s) referenced in the Medical Policy Statement. If there is a conflict between the Medical Policy Statement and the plan contract (i.e., Evidence of Coverage), then the plan contract (i.e., Evidence of Coverage) will be the controlling document used to make the determination.
    [Show full text]
  • Drug Consumption in 2017 - 2020
    Page 1 Drug consumption in 2017 - 2020 2020 2019 2018 2017 DDD/ DDD/ DDD/ DDD/ 1000 inhab./ Hospital 1000 inhab./ Hospital 1000 inhab./ Hospital 1000 inhab./ Hospital ATC code Subgroup or chemical substance day % day % day % day % A ALIMENTARY TRACT AND METABOLISM 322,79 3 312,53 4 303,08 4 298,95 4 A01 STOMATOLOGICAL PREPARATIONS 14,28 4 12,82 4 10,77 6 10,46 7 A01A STOMATOLOGICAL PREPARATIONS 14,28 4 12,82 4 10,77 6 10,46 7 A01AA Caries prophylactic agents 11,90 3 10,48 4 8,42 5 8,45 7 A01AA01 sodium fluoride 11,90 3 10,48 4 8,42 5 8,45 7 A01AA03 olaflur 0,00 - 0,00 - 0,00 - 0,00 - A01AB Antiinfectives for local oral treatment 2,36 8 2,31 7 2,31 7 2,02 7 A01AB03 chlorhexidine 2,02 6 2,10 7 2,09 7 1,78 7 A01AB11 various 0,33 21 0,21 0 0,22 0 0,24 0 A01AD Other agents for local oral treatment 0,02 0 0,03 0 0,04 0 - - A01AD02 benzydamine 0,02 0 0,03 0 0,04 0 - - A02 DRUGS FOR ACID RELATED DISORDERS 73,05 3 71,13 3 69,32 3 68,35 3 A02A ANTACIDS 2,23 1 2,22 1 2,20 1 2,30 1 A02AA Magnesium compounds 0,07 22 0,07 22 0,08 22 0,10 19 A02AA04 magnesium hydroxide 0,07 22 0,07 22 0,08 22 0,10 19 A02AD Combinations and complexes of aluminium, 2,17 0 2,15 0 2,12 0 2,20 0 calcium and magnesium compounds A02AD01 ordinary salt combinations 2,17 0 2,15 0 2,12 0 2,20 0 A02B DRUGS FOR PEPTIC ULCER AND 70,82 3 68,91 3 67,12 3 66,05 4 GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 0,17 7 0,74 4 1,10 4 1,11 5 A02BA02 ranitidine 0,00 1 0,63 3 0,99 3 0,99 4 A02BA03 famotidine 0,16 7 0,11 8 0,11 10 0,12 9 A02BB Prostaglandins 0,04 62
    [Show full text]
  • The Effectiveness of Correcting Abnormal Metabolic Profiles
    Received: 25 April 2019 Revised: 17 June 2019 Accepted: 19 June 2019 DOI: 10.1002/jimd.12139 ORIGINAL ARTICLE The effectiveness of correcting abnormal metabolic profiles Peter Theodore Clayton UCL Great Ormond Street Institute of Child Health, London, UK Abstract Inborn errors of metabolism cause disease because of accumulation of a metabolite Correspondence before the blocked step or deficiency of an essential metabolite downstream of the Peter Clayton, UCL Great Ormond Street Institute of Child Health, London, UK. block. Treatments can be directed at reducing the levels of a toxic metabolite or Email: [email protected] correcting a metabolite deficiency. Many disorders have been treated successfully first in a single patient because we can measure the metabolites and adjust treat- Communicating Editor: Sander M. Houten ment to get them as close as possible to the normal range. Examples are drawn from Komrower's description of treatment of homocystinuria and the author's trials 5 of treatment in bile acid synthesis disorders (3β-hydroxy-Δ -C27-steroid dehydro- genase deficiency and Δ4-3-oxosteroid 5β-reductase deficiency), neurotransmitter amine disorders (aromatic L-amino acid decarboxylase [AADC] and tyrosine hydroxylase deficiencies), and vitamin B6 disorders (pyridox(am)ine phosphate oxidase deficiency and pyridoxine-dependent epilepsy [ALDH7A1 deficiency]). Sometimes follow-up shows there are milder and more severe forms of the disease and even variable clinical manifestations but by measuring the metabolites we can adjust the treatment to get the metabolites into the normal range. Biochemical mea- surements are not subject to placebo effects and will also show if the disorder is improving spontaneously.
    [Show full text]
  • Express Scripts 2020 National Preferred Formulary List
    2020 Express Scripts National Preferred Formulary List The 2020 National Preferred Formulary drug list is shown below. The formulary is the list of drugs included in your prescription plan. Inclusion on the list does not guarantee coverage. The following list is not a complete list of over-the-counter [OTC] products and prescription medical supplies that are on the formulary. The only OTC products and prescription medical supplies that appear on the list are in contracted classes. PLEASE NOTE: Brand-name drugs may move to nonformulary status if a generic version becomes available during the year. Not all the drugs listed are covered by all prescription plans; check your benefit materials for the specific drugs covered and the copayments for your prescription plan. For specific questions about your coverage, please call the phone number printed on your member ID card. KEY For the member: FDA-approved generic medications meet strict standards and [INJ] – Injectable Drug contain the same active ingredients as their corresponding brand-name medications, [OTC] – Over-the-counter Product although they may have a different appearance. [SP] – Specialty Drug For the physician: Please prescribe preferred products and allow generic Brand-name drugs are listed in CAPITAL letters. Example: ABILIFY MAINTENA substitutions when medically appropriate. Generic drugs are listed in lower-case letters. Example: ibuprofen A adenosine [INJ] amabelz anthralin ADVAIR HFA amantadine APLISOL [INJ] abacavir [SP] ADVATE [INJ] [SP] AMBISOME [INJ] APOKYN [INJ] [SP]
    [Show full text]
  • Specialty Drug Benefit Document
    Louisiana Healthcare Connections Specialty Drug Benefit ouisiana Healthcare Connections provides coverage of a number of specialty drugs. All specialty drugs, such as biopharmaceuticals and injectables, require a prior authorization (PA) to be approved for L payment by Louisiana Healthcare Connections. PA requirements are programmed specific to the drug. Since the list of specialty drugs changes over time due to new drug arrivals and other market conditions, it is important to contact Provider Services at 1-866-595-8133 or check the Louisiana Healthcare Connections website at www.LouisianaHealthConnect.com for updates to this benefit. Requests for specialty drugs can be submitted to Louisiana Healthcare Connections by filling out the Medication Prior Authorization Form that is available on the Louisiana Healthcare Connections website at www.LouisianaHealthConnect.com and faxing the request as instructed on the form. Louisiana Healthcare Connections members can receive the specialty drugs they require at any outpatient pharmacy enrolled in our pharmacy network that can supply specialty drugs. Providers that wish to have drugs distributed by a SPECIALTY PHARMACY should FAX the request to 1-866-399-0929 for review. If a provider wishes to dispense a specialty drug from OFFICE STOCK, the provider should FAX the request to Louisiana Healthcare Connections at 1-877-401-8172 for review. BRAND NAME INGREDIENTS SPECIAL INSTRUCTIONS ACTEMRA TOCILIZUMAB ACTHAR HP CORTICOTROPIN ACTIMMUNE INTERFERON GAMMA-1B ADAGEN PEGADEMASE BOVINE Limited Distribution
    [Show full text]
  • L-Citrulline
    L‐Citrulline Pharmacy Compounding Advisory Committee Meeting November 20, 2017 Susan Johnson, PharmD, PhD Associate Director Office of Drug Evaluation IV Office of New Drugs L‐Citrulline Review Team Ben Zhang, PhD, ORISE Fellow, OPQ Ruby Mehta, MD, Medical Officer, DGIEP, OND Kathleen Donohue, MD, Medical Officer, DGIEP, OND Tamal Chakraborti, PhD, Pharmacologist, DGIEP, OND Sushanta Chakder, PhD, Supervisory Pharmacologist, DGIEP, OND Jonathan Jarow, MD, Advisor, Office of the Center Director, CDER Susan Johnson, PharmD, PhD, Associate Director, ODE IV, OND Elizabeth Hankla, PharmD, Consumer Safety Officer, OUDLC, OC www.fda.gov 2 Nomination • L‐citrulline has been nominated for inclusion on the list of bulk drug substances for use in compounding under section 503A of the Federal Food, Drug and Cosmetic Act (FD&C Act) • It is proposed for oral use in the treatment of urea cycle disorders (UCDs) www.fda.gov 3 Physical and Chemical Characterization • Non‐essential amino acid, used in the human body in the L‐form • Well characterized substance • Soluble in water • Likely to be stable under ordinary storage conditions as solid or liquid oral dosage forms www.fda.gov 4 Physical and Chemical Characterization (2) • Possible synthetic routes – L‐citrulline is mainly produced by fermentation of L‐arginine as the substrate with special microorganisms such as the L‐arginine auxotrophs arthrobacterpa rafneus and Bacillus subtilis. – L‐citrulline can also be obtained through chemical synthesis. The synthetic route is shown in the scheme below. This
    [Show full text]
  • Carbaglu; INN-Carglumic Acid
    London, 19 August 2016 EMA/532759/2016 Committee for Medicinal Products for Human Use (CHMP) Assessment report for paediatric studies submitted according to Article 46 of the Regulation (EC) No 1901/2006 Carbaglu carglumic acid Procedure no: EMEA/H/C/000461/P46/033 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8613 E -mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Introduction ............................................................................................ 3 2. Scientific discussion ................................................................................ 3 2.1. Information on the development program ............................................................... 3 2.2. Information on the pharmaceutical formulation used in the study ............................... 3 2.3. Clinical aspects .................................................................................................... 3 2.3.1. Introduction ...................................................................................................... 3 2.3.2. Clinical study .................................................................................................... 4 2.3.3. Discussion on clinical aspects ...........................................................................
    [Show full text]
  • Orphan Drugs Used for Treatment in Pediatric Patients in the Slovak Republic
    DOI 10.2478/v10219-012-0001-0 ACTA FACULTATIS PHARMACEUTICAE UNIVERSITATIS COMENIANAE Supplementum VI 2012 ORPHAN DRUGS USED FOR TREATMENT IN PEDIATRIC PATIENTS IN THE SLOVAK REPUBLIC 1Foltánová, T. – 2Konečný, M. – 3Hlavatá, A. –.4Štepánková, K. 5Cisárik, F. 1Comenius University in Bratislava, Faculty of Pharmacy, Department of Pharmacology and Toxicology 2Department of Clinical Genetics, St. Elizabeth Cancer Institute, Bratislava 32nd Department of Pediatrics, UniversityChildren'sHospital, Bratislava 4Slovak Cystic Fibrosis Association, Košice 5Department of Medical Genetics, Faculty Hospital, Žilina Due to the enormous success of scientific research in the field of paediatric medicine many once fatal children’s diseases can now be cured. Great progress has also been achieved in the rehabilitation of disabilities. However, there is still a big group of diseases defined as rare, treatment of which has been traditionally neglected by the drug companies mainly due to unprofitability. Since 2000 the treatment of rare diseases has been supported at the European level and in 2007 paediatric legislation was introduced. Both decisions together support treatment of rare diseases in children. In this paper, we shortly characterise the possibilities of rare diseases treatment in children in the Slovak republic and bring the list of orphan medicine products (OMPs) with defined dosing in paediatrics, which were launched in the Slovak market. We also bring a list of OMPs with defined dosing in children, which are not available in the national market. This incentive may help in further formation of the national plan for treating rare diseases as well as improvement in treatment options and availability of rare disease treatment in children in Slovakia.
    [Show full text]