D I R E C T O R Y O F APPROVED BIOPHARMACEUTICAL PRODUCTS D I R E C T O R Y O F APPROVED BIOPHARMACEUTICAL PRODUCTS Stefania Spada and Gary Walsh CRC PR ESS Boca Raton London New York Washington, D.C. TF1309_C00.fm Page 4 Monday, July 19, 2004 8:42 AM Warning! This publication is intended for general reference only and should never be used as a guide for prescribing or administering the drugs listed. Cover figure from: Protein Data Bank (www.rcsb.org/pdb) PDB ID 1HIG Ealick, S.E., Cook, W.J., Vijay-Kumar, S., Carson, M., Nagabhushan, T.L., Trotta, P.P., Bugg, C.E. Three-Dimensional Structure Recombinant Human Interferon-Gamma. Science 252 pp. 698 (1991) Library of Congress Cataloging-in-Publication Data Spada, Stefania. Directory of approved biopharmaceutical products / by Stefania Spada and Gary Walsh. p. ; cm. Includes bibliographical references. ISBN 0-415-26368-9 (alk. paper) 1. Protein drugs—Catalogs. 2. Nucleic acids—Therapeutic use—Catalogs. I. Walsh, Gary, Dr. II. Title. [DNLM: 1. Nucleic Acids—therapeutic use—Catalogs. 2. Pharmaceutical Preparations—Catalogs. 3. Proteins—therapeutic use—Catalogs. QV 772 S732d 2004] RS431.P75S635 2004 615¢.19--dc22 2004050317 This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. 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Visit the CRC Press Web site at www.crcpress.com © 2005 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 0-415-26368-9 Library of Congress Card Number 2004050317 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paper TF1309_C00.fm Page 5 Monday, July 19, 2004 8:42 AM We dedicate this book to our families — Gerard, Cristina, Maria, Nancy, Eithne, and Shane © 2005 by CRC Press LLC TF1309_C00.fm Page 7 Monday, July 19, 2004 8:42 AM Preface The term "biopharmaceutical" has become an accepted part of the pharma- ceutical vocabulary. It refers to therapeutic proteins produced by genetic engineering (or via hybridoma technology, in the case of some monoclonal antibodies), as well as nucleic acid-based products. By mid-2003, some 118 biopharmaceutical products had gained marketing approval and one in approximately every four genuinely new drugs coming on the market are now produced by biotechnological means. Despite the prominence of biopharmaceuticals in the modern pharmaceu- tical era, relatively few publications focus, to any meaningful extent, on actual commercial products. This book aims to do just that — to provide a brief summary of each biopharmaceutical product approved for medical use. Product information is provided in monograph format. We have attempted to keep the profiles relatively consistent throughout the directory; however, some variations occur due to the information available from primary liter- ature reference sources. The majority of information provided has been sourced from regulatory Web sites, including the European Medicines Eval- uation Agency (EMEA) and the U.S. Food and Drug Administration (FDA), as well as from the Web sites of relevant pharmaceutical companies. Avail- ability only within the E.U. and U.S. is discussed, although many of the listed products have also gained approval in other world regions. Approvals listed for E.U. products refer specifically to products approved through the new, centralized European drug approval system, introduced in 1995. Some products (particularly earlier products, such as recombinant human growth hormone preparations) gained approval in some European countries prior to 1995 and are still available in those countries. As authors, we have ensured to the best of our ability that all the infor- mation provided is accurate. This directory, however, is intended as a general reference only and should never be used as a guide for prescribing or admin- istering the drugs listed. Updated information (e.g., modified indications, safety warnings, etc.) on any of the drugs can be obtained by consulting the Web sites of the relevant regulatory authorities or the companies that market the products. This directory is aimed primarily at individuals employed within the biopharmaceutical sector and at those with an interest in this sector and the products it produces. It will also serve as a useful reference for students pursuing courses in biotechnology, medicine, pharmacy, or pharmaceutical science. © 2005 by CRC Press LLC TF1309_C00.fm Page 9 Monday, July 19, 2004 8:42 AM Authors Stefania Spada obtained a degree in biological sciences from the University of Milan, Italy. She engineered antibodies for carcinoma therapy at the Department of Biological and Technological Research, in the San Raffaele Scientific Institute in Milan. While working on her Ph.D. in biochemistry at the University of Zurich, Switzerland, she developed a novel phage dis- play-based system of selection of interacting ligand pairs. Spada held a postdoctoral position at the University of Limerick, Ireland, where she iden- tified and characterized proteins with novel biotechnological properties from thermophilic bacteria. Gary Walsh obtained his Ph.D. from the National University of Ireland at Galway. He worked in the pharmaceutical and biotechnology industries for a number of years and is a senior lecturer of biotechnology at the University of Limerick. Walsh has published numerous articles and books on various aspects of pharmaceutical biotechnology. He sits on the editorial board of two international pharmaceutical journals and is scientific secretary of the European Association of Pharma Biotechnology. © 2005 by CRC Press LLC TF1309_C00.fm Page 11 Monday, July 19, 2004 8:42 AM Table of contents Monographs are listed alphabetically by trade name Actimmune Activase Aldurazyme Ambirix Amevive Avonex BeneFIX Beromun Betaferon/Betaseron Bexxar Bio-Tropin (Tev-Tropin or Zomacton) Bioclate CEA-Scan Cerezyme Comvax Ecokinase (withdrawn from market) Enbrel Engerix-B Epogen/Procrit Fabrazyme Fasturtec/Elitek Forcaltonin Forsteo/Forteo Genotropin GlucaGen Glucagon Gonal-F HBVAXPRO Helixate NexGen/Helixate FS/Kogenate FS Hepacare (withdrawn from market) Herceptin Hexavac Humalog HumaSPECT Humatrope Humira Humulin Indimacis 125 (withdrawn from market) © 2005 by CRC Press LLC TF1309_C00.fm Page 12 Monday, July 19, 2004 8:42 AM InductOs INFANRIX HepB Infanrix Hexa Infanrix Penta/Pediarix Infergen InFUSE Bone Graft/LT-CAGE Lumbar Tapered Fusion Device Insuman Intron A Kineret Lantus Leukine LeukoScan Liprolog (withdrawn from market) Luveris LYMErix (withdrawn from market) MabCampath/Campath-1H MabThera/Rituxan Metalyse/TNKase Mylotarg Myoscint (withdrawn from market) Natrecor NeoRecormon Nespo/Aranesp Neulasta Neumega Neupogen Norditropin Novolin/Actrapid/Insulatard/Mixtard/Monotard/ Ultratard/Velosulin NovoRapid/Novolog and NovoMix 30/NovoLog Mix 70/30 Novoseven Nutropin Depot NutropinAQ OncoScint CR/OV Ontak Optisulin Orthoclone OKT-3 Osigraft/OP-1 Implant Ovitrelle/Ovidrel Pegasys PegIntron Primavax (withdrawn from market) PROCOMVAX/COMVAX Proleukin ProstaScint Protropin © 2005 by CRC Press LLC TF1309_C00.fm Page 13 Monday, July 19, 2004 8:42 AM Pulmozyme Puregon/Follistim Rapilysin/Retavase Rebetron Rebif Recombinate Recombivax ReFacto Refludan Regranex Remicade ReoPro Replagal Revasc Roferon A Saizen Serostim Simulect Somavert Synagis Tecnemab K1 (withdrawn from market) Thyrogen Triacelluvax (withdrawn from market) Tritanrix HepB Twinrix Adult Twinrix Paediatric Verluma Viraferon ViraferonPeg Vitravene (withdrawn from E.U. market) Xigris Xolair Zenapax Zevalin Appendix © 2005 by CRC Press LLC TF1309_C01.fm Page 1 Monday, July 19, 2004 8:43 AM Actimmune Product Name: Actimmune (trade name) Interferon gamma-1b (international nonproprietary name) Description: Actimmune is a recombinant, 140-amino acid, inter- feron gamma-1b (IFN-g1b). It is produced in a mod- ified Escherichia coli strain and differs from the natural human molecule in containing an additional methionine residue at the N-terminal. It is supplied as a sterile solution filled in a single dose vial for subcutaneous administration. Each 0.5 ml of Actim- mune contains 2 million International Units (IU) of interferon gamma-1b. Approval Date: 1990 (U.S.). It is now also approved in various other countries. Therapeutic Actimmune is indicated for reducing the frequency Indications: and severity of serious infections associated with chronic granulomatous disease. Manufacturer: InterMune, 3294 West Bayshore Road, Palo Alto, CA 94303, http://www.intermune.com (U.S.) Marketing: InterMune, 3294 West Bayshore Road, Palo Alto, CA 94303, http://www. intermune.com (U.S.) Manufacturing Actimmune is a recombinant interferon gamma-1b. It is produced in a mod- ified E. coli (strain K-12) that has been transformed with the human IFN-g gene, and it differs from the natural human molecule by containing an additional methionine residue at its N terminus. After fermentation, the product is purified using several chromatographic and ultrafiltration steps, and the final product consists of two identical 140 amino acid chains linked via noncovalent bonds to form a homodimer. Actimmune is provided as a © 2005 by CRC Press LLC