DOCSLIB.ORG

Zolgensma, INN-Onasemnogene Abeparvovec

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Zolgensma, INN-Onasemnogene Abeparvovec 26 March 2020 EMA/200482/2020 Committee for Medicinal Products for Human Use (CHMP) Committee for Advanced Therapies (CAT) Assessment report Zolgensma International non-proprietary name: onasemnogene abeparvovec Procedure No. EMEA/H/C/004750/0000 Note The CAT Assessment report has been endorsed by the CHMP with all information of a commercially confidential nature deleted. Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 6 1.1. Submission of the dossier ...................................................................................... 6 1.2. Steps taken for the assessment of the product ......................................................... 9 2. Scientific discussion .............................................................................. 10 2.1. Problem statement ............................................................................................. 10 2.1.1. Disease or condition ......................................................................................... 10 2.1.2. Epidemiology .................................................................................................. 11 2.1.3. Biologic features .............................................................................................. 11 2.1.4. Clinical presentation and diagnosis .................................................................... 12 2.1.5. Management ................................................................................................... 13 2.2. Quality aspects .................................................................................................. 14 2.2.1. Introduction .................................................................................................... 14 2.2.2. Active Substance ............................................................................................. 14 2.2.1. Finished Medicinal Product ................................................................................ 18 2.2.2. Discussion on chemical, pharmaceutical and biological aspects .............................. 23 2.2.3. Conclusions on the chemical, pharmaceutical and biological aspects ...................... 24 2.2.4. Recommendation(s) for future quality development ............................................. 25 2.3. Non-clinical aspects ............................................................................................ 26 2.3.1. Pharmacology ................................................................................................. 26 2.3.2. Pharmacokinetics............................................................................................. 32 2.3.3. Toxicology ...................................................................................................... 35 2.3.4. Ecotoxicity/environmental risk assessment ......................................................... 43 2.3.5. Discussion on the non-clinical aspects ................................................................ 49 2.3.6. Conclusion on non-clinical aspects ..................................................................... 54 2.4. Clinical aspects .................................................................................................. 55 2.4.1. Introduction .................................................................................................... 55 2.4.2. Pharmacokinetics............................................................................................. 59 2.4.3. Pharmacodynamics .......................................................................................... 60 2.4.4. Discussion on clinical pharmacology ................................................................... 63 2.4.5. Conclusions on clinical pharmacology ................................................................. 64 2.5. Clinical efficacy .................................................................................................. 65 2.5.1. Dose finding ................................................................................................... 65 2.5.2. Main studies ................................................................................................... 65 2.5.3. Supportive studies ........................................................................................... 78 2.5.4. Discussion on clinical efficacy ............................................................................ 96 2.5.5. Conclusions on the clinical efficacy ................................................................... 102 2.6. Clinical safety .................................................................................................. 103 2.6.1. Discussion on clinical safety ............................................................................ 125 2.6.2. Conclusions on the clinical safety ..................................................................... 128 2.7. Risk Management Plan ...................................................................................... 132 2.8. Pharmacovigilance ............................................................................................ 133 2.9. New Active Substance ....................................................................................... 133 2.10. Product information ........................................................................................ 133 2.10.1. User consultation ......................................................................................... 133 EMA/200482/2020 Page 2/150 2.10.2. Labelling exemptions .................................................................................... 134 2.10.3. Additional monitoring ................................................................................... 134 3. Benefit risk assessment ....................................................................... 134 3.1. Therapeutic Context ......................................................................................... 134 3.1.1. Disease or condition ....................................................................................... 134 3.1.2. Available therapies and unmet medical need ..................................................... 135 3.1.3. Main clinical studies ....................................................................................... 135 3.2. Favourable effects ............................................................................................ 136 3.3. Uncertainties and limitations about favourable effects ........................................... 138 3.4. Unfavourable effects ......................................................................................... 139 3.5. Uncertainties and limitations about unfavourable effects ....................................... 140 3.6. Effects Table .................................................................................................... 140 3.7. Co-primary endpoint: proportion of patients achieving independent sitting .............. 141 3.8. Benefit-risk assessment and discussion ............................................................... 142 3.8.1. Importance of favourable and unfavourable effects ............................................ 142 3.8.2. Balance of benefits and risks ........................................................................... 144 3.8.3. Additional considerations ................................................................................ 145 3.9. Conclusions ..................................................................................................... 148 4. Recommendations ............................................................................... 148 EMA/200482/2020 Page 3/150 List of abbreviations Abbreviation Definition AAV adeno-associated virus AAV9 adeno-associated virus serotype 9 ACTIVE-mini Ability Captured Through Interactive Video Evaluation – mini ADaM Analysis Data Model AE adverse event ALT alanine aminotransferase AST aspartate aminotransferase ASO antisense oligonucleotide BiPAP bi-level positive airway pressure CDISC Clinical Data Interchange Standards Consortium CHOP-INTEND Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders CMAP compound motor action potential CMV cytomegalovirus CSF cerebrospinal fluid CSR clinical study report ddPCR droplet digital polymerase chain reaction DILI drug-induced liver injury DSMB Data Safety Monitoring Board ECAS efficacy completer analysis set ECG electrocardiogram EES efficacy evaluable set EIM electrical impedance myography EMA European Medicines Agency EU European Union FAS full analysis set FDA Food and Drug Administration GMP Good Manufacturing Practice ICD-10 10th Revision of the International Classification of Diseases and Related Health Problems ICH International Council for Harmonization IQR interquartile range IRB Institutional Review. Board Inspections IT intrathecal ITR inverted terminal repeats ITT intent-to-treat IV intravenous LOCF last observation carried forward LS least squares Max maximum Min minimum mITT modified intent-to-treat MMRM mixed model repeated measure mRNA messenger ribonucleic acid MUNE motor unit number
Load more

Recommended publications
  • Spinraza™ (Nusinersen)
    Spinraza™ (nusinersen) (Intrathecal) Document Number: IC-0291 Last Review Date: 08/03/2021 Date of Origin: 01/31/2017 Dates Reviewed: 01/2017, 02/2017, 01/2018, 08/2018, 06/2019, 08/2020, 08/2021 I. Length of Authorization Coverage will be provided annually and may be renewed. II. Dosing Limits A. Quantity Limit (max daily dose) [NDC Unit]: • Loading: 1 vial on D1, D15, D29, and D59 • Maintenance: 1 vial every 112 days B. Max Units (per dose and over time) [HCPCS Unit]: • Loading: 120 billable units on D1, D15, D29, and D59 • Maintenance: 120 billable units every 112 days III. Initial Approval Criteria1-12 • Submission of medical records related to the medical necessity criteria is REQUIRED on all requests for authorizations. Records will be reviewed at the time of submission. Please provide documentation via direct upload through the PA web portal or by fax. Coverage is provided in the following conditions: Spinal Muscular Atrophy (SMA) † Ф • Patient must not have previously received treatment with SMA gene therapy (i.e., onasemnogene abeparvovec-xioi); AND • Patient will not use in combination with other agents for SMA (e.g., onasemnogene abeparvovec, risdiplam, etc.); AND • Patient must not have advanced disease (complete limb paralysis, permanent ventilation support, etc.); AND Moda Health Plan, Inc. Medical Necessity Criteria Page 1/5 Proprietary & Confidential © 2021 Magellan Health, Inc. • Patient must have the following laboratory tests at baseline and prior to each administration*: platelet count, prothrombin time; activated
    [Show full text]
  • 2017 ANNUAL REPORT | Translating SCIENCE • Transforming LIVES OUR COMMITMENT Make Every Day Count at PTC, Patients Are at the Center of Everything We Do
    20 YEARS OF COMMITMENT 2017 ANNUAL REPORT | Translating SCIENCE • Transforming LIVES OUR COMMITMENT Make every day count At PTC, patients are at the center of everything we do. We have the opportunity to support patients and families living with rare disorders through their journey. We know that every day matters and we are committed to making a difference. OUR SCIENCE Our scientists are finding new ways to regulate biology to control disease We have several scientific research platforms focused on modulating protein expression within the cell that we believe have the potential to address many rare genetic disorders. OUR PEOPLE Care for each other, our community, and for the needs of our patients At PTC, we are looking at drug discovery and development in a whole new light, bringing new technologies and approaches to developing medicines for patients living with rare disorders and cancer. We strive every day to be better than we were the day before. At PTC Therapeutics, it is our mission to provide access to best-in-class treatments for patients who have an unmet need. We are a science-led, global biopharmaceutical company focused on the discovery, development and commercialization of clinically-differentiated medicines that provide benefits to patients with rare disorders. Founded 20 years ago, PTC Therapeutics has successfully launched two rare disorder products and has a global commercial footprint. This success is the foundation that drives investment in a robust pipeline of transformative medicines and our mission to provide access to best-in-class treatments for patients who have an unmet medical need. As we celebrate our 20th year of bringing innovative therapies to patients affected by rare disorders, we reflect on our unwavering commitment to our patients, our science and our employees.
    [Show full text]
  • Spinraza® (Nusinersen)
    UnitedHealthcare® Commercial Medical Benefit Drug Policy Spinraza® (Nusinersen) Policy Number: 2021D0059I Effective Date: July 1, 2021 Instructions for Use Table of Contents Page Community Plan Policy Coverage Rationale ....................................................................... 1 • Spinraza® (Nusinersen) Documentation Requirements ...................................................... 3 Applicable Codes .......................................................................... 3 Background.................................................................................... 4 Benefit Considerations .................................................................. 5 Clinical Evidence ........................................................................... 5 U.S. Food and Drug Administration ............................................. 8 References ..................................................................................... 9 Policy History/Revision Information ........................................... 10 Instructions for Use ..................................................................... 11 Coverage Rationale See Benefit Considerations Spinraza® (nusinersen) is proven and medically necessary for the treatment of spinal muscular atrophy (SMA) in patients who meet all of the following criteria: 1-4,22,23 Initial Therapy Diagnosis of spinal muscular atrophy by, or in consultation with, a neurologist with expertise in the diagnosis of SMA; and Submission of medical records (e.g., chart notes, laboratory values)
    [Show full text]
  • DRUGS REQUIRING PRIOR AUTHORIZATION in the MEDICAL BENEFIT Page 1
    Effective Date: 08/01/2021 DRUGS REQUIRING PRIOR AUTHORIZATION IN THE MEDICAL BENEFIT Page 1 Therapeutic Category Drug Class Trade Name Generic Name HCPCS Procedure Code HCPCS Procedure Code Description Anti-infectives Antiretrovirals, HIV CABENUVA cabotegravir-rilpivirine C9077 Injection, cabotegravir and rilpivirine, 2mg/3mg Antithrombotic Agents von Willebrand Factor-Directed Antibody CABLIVI caplacizumab-yhdp C9047 Injection, caplacizumab-yhdp, 1 mg Cardiology Antilipemic EVKEEZA evinacumab-dgnb C9079 Injection, evinacumab-dgnb, 5 mg Cardiology Hemostatic Agent BERINERT c1 esterase J0597 Injection, C1 esterase inhibitor (human), Berinert, 10 units Cardiology Hemostatic Agent CINRYZE c1 esterase J0598 Injection, C1 esterase inhibitor (human), Cinryze, 10 units Cardiology Hemostatic Agent FIRAZYR icatibant J1744 Injection, icatibant, 1 mg Cardiology Hemostatic Agent HAEGARDA c1 esterase J0599 Injection, C1 esterase inhibitor (human), (Haegarda), 10 units Cardiology Hemostatic Agent ICATIBANT (generic) icatibant J1744 Injection, icatibant, 1 mg Cardiology Hemostatic Agent KALBITOR ecallantide J1290 Injection, ecallantide, 1 mg Cardiology Hemostatic Agent RUCONEST c1 esterase J0596 Injection, C1 esterase inhibitor (recombinant), Ruconest, 10 units Injection, lanadelumab-flyo, 1 mg (code may be used for Medicare when drug administered under Cardiology Hemostatic Agent TAKHZYRO lanadelumab-flyo J0593 direct supervision of a physician, not for use when drug is self-administered) Cardiology Pulmonary Arterial Hypertension EPOPROSTENOL (generic)
    [Show full text]
  • New Brunswick Drug Plans Formulary
    New Brunswick Drug Plans Formulary August 2019 Administered by Medavie Blue Cross on Behalf of the Government of New Brunswick TABLE OF CONTENTS Page Introduction.............................................................................................................................................I New Brunswick Drug Plans....................................................................................................................II Exclusions............................................................................................................................................IV Legend..................................................................................................................................................V Anatomical Therapeutic Chemical (ATC) Classification of Drugs A Alimentary Tract and Metabolism 1 B Blood and Blood Forming Organs 23 C Cardiovascular System 31 D Dermatologicals 81 G Genito Urinary System and Sex Hormones 89 H Systemic Hormonal Preparations excluding Sex Hormones 100 J Antiinfectives for Systemic Use 107 L Antineoplastic and Immunomodulating Agents 129 M Musculo-Skeletal System 147 N Nervous System 156 P Antiparasitic Products, Insecticides and Repellants 223 R Respiratory System 225 S Sensory Organs 234 V Various 240 Appendices I-A Abbreviations of Dosage forms.....................................................................A - 1 I-B Abbreviations of Routes................................................................................A - 4 I-C Abbreviations of Units...................................................................................A
    [Show full text]
  • Circulating Biomarkers in Neuromuscular Disorders: What Is Known, What Is New
    biomolecules Review Circulating Biomarkers in Neuromuscular Disorders: What Is Known, What Is New Andrea Barp 1,* , Amanda Ferrero 1, Silvia Casagrande 1,2 , Roberta Morini 1 and Riccardo Zuccarino 1 1 NeuroMuscular Omnicentre (NeMO) Trento, Villa Rosa Hospital, Via Spolverine 84, 38057 Pergine Valsugana, Italy; [email protected] (A.F.); [email protected] (S.C.); [email protected] (R.M.); [email protected] (R.Z.) 2 Department of Neurosciences, Drug and Child Health, University of Florence, Largo Brambilla 3, 50134 Florence, Italy * Correspondence: [email protected] Abstract: The urgent need for new therapies for some devastating neuromuscular diseases (NMDs), such as Duchenne muscular dystrophy or amyotrophic lateral sclerosis, has led to an intense search for new potential biomarkers. Biomarkers can be classified based on their clinical value into different categories: diagnostic biomarkers confirm the presence of a specific disease, prognostic biomarkers provide information about disease course, and therapeutic biomarkers are designed to predict or measure treatment response. Circulating biomarkers, as opposed to instrumental/invasive ones (e.g., muscle MRI or nerve ultrasound, muscle or nerve biopsy), are generally easier to access and less “time-consuming”. In addition to well-known creatine kinase, other promising molecules seem to be candidate biomarkers to improve the diagnosis, prognosis and prediction of therapeutic response, such as antibodies, neurofilaments, and microRNAs. However, there are some criticalities that can complicate their application: variability during the day, stability, and reliable performance metrics Citation: Barp, A.; Ferrero, A.; (e.g., accuracy, precision and reproducibility) across laboratories. In the present review, we discuss Casagrande, S.; Morini, R.; Zuccarino, the application of biochemical biomarkers (both validated and emerging) in the most common NMDs R.
    [Show full text]
  • Spotlight on Market Access Actionable Understandings from AIS Health’S In-Depth Coverage
    Spotlight on Market Access Actionable understandings from AIS Health’s in-depth coverage September 16, 2019 Recent Situations Stress That Data Is More Important Than Ever to FDA, Drug Uptake 2 Clinical Trials by Indication: Q2 2019 A pair of drugmakers and the FDA found themselves in the news lately, but it’s safe to say it wasn’t for the reasons they would prefer. Both situations Reality Check: PCSK9 Inhibitors 8 stress the importance of data needed to secure product approvals, and, per- haps, payer and provider uptake. On Aug. 6, the FDA put out a statement addressing “data accuracy issues” with Zolgensma (onasemnogene abeparvovec-xioi), a new gene ther- apy to treat spinal muscular atrophy in people less than 2 years old who have bi-allelic mutations in the survival motor neuron 1 gene, including those who are presymptomatic when diagnosed. The one-time therapy has the distinction of being the most expensive drug in the world, with a price tag of $2.1 million. The FDA approved the drug from AveXis, Inc. on May 24 (SMA 7/1/19, p. 6). On June 28, AveXis — which was acquired by Novartis AG last year — notified the agency that there was “a data manipulation issue that impacts the accuracy of certain data from product testing performed in animals sub- mitted in the biologics license application (BLA) and reviewed by the FDA.” continued on p. 3 Report Reveals That Almost 100 RM/AT Products Are in Phase III Clinical Trials This past quarter saw two new gene therapies: Novartis AG subsidiary AveXis, Inc.’s Zolgensma (onasemnogene abeparvovec-xioi) received FDA approval May 24 for the treatment of spinal muscular atrophy (SMA 7/1/19, p.
    [Show full text]
  • Corporate Medical Policy
    Corporate Medical Policy Nusinersen (Spinraza™) File Name: nusinersen_spinraza Origination: 03/2017 Last CAP Review: 10/2020 Next CAP Review: 10/2021 Last Review: 10/2020 Description of Procedure or Service Spinal muscular atrophy (SMA) is an inherited disorder caused by homozygous deletions or variants in the SMN1 gene. As a consequence of low levels of SMN1 protein, the motor neurons in spinal cord degenerate, resulting in atrophy of the voluntary muscles of the limbs and trunk. Nusinersen is a synthetic antisense oligonucleotide designed to bind to a specific sequence in exon 7 of the SMN2 transcript causing the inclusion of exon 7 in the SMN2 transcript, leading to production of full length functional SMN2 protein, which demonstrates similarity to SMN1. SPINAL MUSCULAR ATROPHY Spinal muscular atrophy (SMA) is a rare autosomal recessive genetic disorder caused by homozygous deletions or variants in the SMN1 gene in chromosome 5. This gene is responsible for producing the “survival of motor neuron” protein (SMN1). As a consequence of absent or low levels of this protein, the motoneurons in the spinal cord degenerate, resulting in atrophy of the voluntary muscles of the limbs and trunk. During early development, these muscles are necessary for crawling, walking, sitting up, and head control. The more severe types of SMA can also affect muscles involved in feeding, swallowing, and breathing. The exact role of the SMN protein in motoneurons has not been completely elucidated and levels of the SMN protein required for optimal functioning are unknown. SMN2 is a nearly identical modifying gene capable of producing compensatory SMN protein.
    [Show full text]
  • Curriculum Vitae
    Curriculum Vitae PERSONAL INFORMATION Ulrike Schara WORK EXPERIENCE 1991- 1997 Education in Paediatrics Paediatric Outpatient Centre,City Hospital Gelsenkirchen. (Germany) Paediatric Outpatient Centre. City Hospital Gelsenkirchen.<br/>Childrens Hospital, Ruhr University Bochum<br/> 1998- 2002 Senior Neuropediatrics Children&apos;s University Hospital Bochum (Germany) . 2002- 2003 Head of Neuropediatrics Children&apos;s University Hospital Bochum (Germany) 2004- 2006 Head of Neuropediatrics Children&apos;s Hospital, City of Neuss (Germany) 2007- Present Head of the Neuropaediatric Outpatient Centre and Consultant for Neuropaediatrics University of Essen (Germany) EDUCATION AND TRAINING 1991- 2012 MD, Professor Ruhr University of Bochum, Germany University of Essen (Germany) ADDITIONAL INFORMATION Expertise Publications Publcations of the past 5 years 1.Rudnik-Schöneborn S, Tölle D, Senderek J, Eggermann K, Elbracht M, Kornak U, von der Hagen M, Kirschner J, Leube B, Müller-Felber W, Schara U, von Au K, Wieczorek D, Bußmann C, Zerres K. Diagnostic algorithms in Charcot-Marie-Tooth neuropathies: experiences from a German genetic laboratory on the basis of 1206 index patients. Clin Genet. 2016 Jan;89(1):34-43 2.Byrne S, Jansen L, U-King-Im JM, Siddiqui A, Lidov HG, Bodi I, Smith L, Mein R, Cullup T, Dionisi-Vici C, Al-Gazali L, Al-Owain M, Bruwer Z, Al Thihli K, El-Garhy R, Flanigan KM, Manickam K, Zmuda E, Banks W, Gershoni-Baruch R, Mandel H, Dagan E, Raas-Rothschild A, Barash H, Filloux F, Creel D, Harris M, Hamosh A, Kölker S, Ebrahimi-Fakhari D, Hoffmann GF, Manchester D, Boyer PJ, Manzur AY, Lourenco CM, Pilz DT, Kamath A, Prabhakar P, Rao VK, Rogers RC, Ryan MM, Brown NJ, McLean CA, Said E, Schara U, Stein A, Sewry C, Travan L, Wijburg FA, Zenker M, Mohammed S, Fanto M, Gautel M, Jungbluth H.
    [Show full text]
  • Immunoprophylaxis of Influenza Using AAV Vector Delivery of Cross
    Immunoprophylaxis of Influenza using AAV Vector Delivery of Cross-Subtype Neutralizing Single Domain Antibodies JOANNE MARIE M. DEL ROSARIO Thesis submitted for the degree of Doctor of Philosophy Infection and Immunity University College London 2020 To Chris, as fate would have it. To Teki, thank you for everything. 2 DECLARATION I, Joanne Marie M. Del Rosario, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. __________________________ 3 ABSTRACT Cross-subtype neutralizing single domain antibodies against influenza present new opportunities for immunoprophylaxis and pandemic preparedness. Their simple modular structure and single open reading frame format are highly amenable to gene therapy-mediated delivery. R1a-B6, an alpaca-derived single domain antibody (nanobody), that is capable of potent cross-subtype neutralization in vitro of H1N1, H5N1, H2N2, and H9N2 influenza viruses, through binding to a highly conserved epitope in the influenza hemagglutinin stem region, was previously described. To evaluate the potential of R1a-B6 for immunoprophylaxis via adeno-associated viral (AAV) vector delivery, it was reformatted as Fc fusions of mouse IgG1 (ADCC-) and IgG2a (ADCC+) isotypes. This is also to extend R1a-B6’s half-life and to assess the requirement for ADCC for efficacy of R1a-B6 in vitro and in vivo. It was found that reformatted R1a-B6 of either mouse IgG isotype retained its potent binding and neutralization activity against different Group I influenza A subtypes in vitro. The findings in this study also demonstrate that a single intramuscular injection in mice of AAV encoding R1a-B6-Fc was able to drive sustained high-level expression (0.5–1.1 mg/mL) of the nanobody-Fc in sera with no evidence of reduction for up to 6 months.
    [Show full text]
  • Innovationsreport 2020 Kurzfassung
    Innovationsreport 2020 Auswertungsergebnisse von Routinedaten der Techniker Krankenkasse aus den Jahren 2017 bis 2018 Herausgeber: Gerd Glaeske Erstellt mit freundlicher Unterstützung der Techniker Krankenkasse (TK) 3 Herausgeber Prof. Dr. Gerd Glaeske Experten für ausgewählte Kapitel Prof. Dr. med. Janbernd Kirschner, Bonn Prof. Dr. med. Dieter Ukena, Bremen Prof. Dr. med. Barbara Schmalfeldt, Hamburg Prof. Dr. med. Wolfgang Schramm, München Autoren Prof. Dr. med. Karl Broich, Dr. Stanislava Dicheva‐Radev, Dörte Fuchs, Prof. Dr. Gerd Glaeske, Dr. Marion Haberkamp, Dr. Iris Hinneburg, Friederike Höfel, Prof. Dr. Janbernd Kirschner, Dr. Wiebke Löbker, Anja Lübs, Dr. André S. Morawetz, Lutz Muth, Dr. Frauke Naumann‐Winter, Linda Richter, Saskia Ritter, Dr. Kristin Sauer, Dr. Birgit Schindler unter Mitarbeit von Esra Aksoy, Friederike Höfel, Berit Marquardt, Linda Richter, Marle Wilhelm Anschrift: Universität Bremen, SOCIUM, Mary‐Somerville‐Str. 5, 28359 Bremen Aus Gründen der besseren Lesbarkeit wurde auf die Nennung beider geschlechtsspezifischer Formen verzichtet. Im Allgemeinen ist aber das jeweils andere Geschlecht ebenfalls gemeint. 2 Glossar .......................................................................................... 7 Vorwort zum Innovationsreport 2020 ...........................................15 Vorwort des Herausgebers ............................................................17 1 Einleitung ................................................................................19 2 Ziele und Methodik..................................................................33
    [Show full text]
  • Outpatient Drug Services Handbook
    Texas Medicaid Provider Procedures Manual December 2020 Provider Handbooks Outpatient Drug Services Handbook The Texas Medicaid & Healthcare Partnership (TMHP) is the claims administrator for Texas Medicaid under contract with the Texas Health and Human Services Commission. TEXAS MEDICAID PROVIDER PROCEDURES MANUAL: VOL. 2 DECEMBER 2020 OUTPATIENT DRUG SERVICES HANDBOOK Table of Contents 1 General Information . 7 1.1 About the Vendor Drug Program. 7 1.2 Pharmacy Enrollment . 8 1.3 Program Contact Information. 8 2 Enrollment . 8 3 Services, Benefits, Limitations, and Prior Authorization. .8 3.1 Prior Authorization Requests . 9 3.2 Electronic Signatures in Prior Authorizations . 9 4 Reimbursement. .10 5 Injectable Medications as a Pharmacy Benefit. .11 6 National Drug Code (NDC) . .12 6.1 Calculating Billable HCPCS and NDC Units . .12 6.1.1 Single-Dose Vials Calculation Examples . 12 6.1.2 Multi-Dose Vials Calculation Examples . 13 6.1.3 Single and Multi-Use Vials . 13 6.1.4 Nonspecific, Unlisted, or Miscellaneous Procedure Codes . 14 7 Outpatient Drugs—Benefits and Limitations. .15 7.1 Abatacept (Orencia) . .15 7.1.1 Prior Authorization for Abatacept (Orencia) . 15 7.2 Adalimumab. .16 7.3 Ado-trastuzumab entansine (Kadcyla). .17 7.4 Alglucosidase Alfa (Myozyme) . .18 7.5 Amifostine . .18 7.6 Antibiotics and Steroids . .22 7.7 Antisense Oligonucleotides (eteplirsen, golodirsen, and nusinersen) . .22 7.7.1 Prior Authorization Requirements. 22 7.7.1.1 Initial Requests (for all Antisense Oligonucleotides) . 23 7.7.1.2 Recertification/Extension Requests (for all Antisense Oligonucleotides). 25 7.7.1.3 Exclusions . 25 7.8 Aripiprazole Lauroxil, (Aristada Initio).
    [Show full text]