ENHANZE® Drug Delivery Technology

Description

‘ENHANZE® drug delivery technology: Advancing subcutaneous drug delivery using recombinant human hyaluronidase PH20’ provides readers with in-depth information on the potential benefits and challenges of subcutaneous (SC) drug delivery, the biology of hyaluronan and hyaluronidases in the SC space, and a comprehensive overview on the history of hyaluronidases and the development of recombinant human hyaluronidase PH20 (rHuPH20). Current applications of rHuPH20 as well as approved biotherapeutics utilizing HuPH20-facilitated SC drug delivery are summarized, and the underlying non-clinical and clinical development approaches are introduced as a basis for future application to biologics in various disease areas. Table of Contents: • Introduction to subcutaneous drug delivery • Biology of hyaluronan and hyaluronidases in the subcutaneous space • History of hyaluronidases and development of rHuPH20 • The ENHANZE® platform: Clinical applications of a subcutaneous drug delivery technology • Application of ENHANZE® drug delivery technology: Development of currently marketed products

Sujets

• Médecine
• Médecine de laboratoire
• Medical
• Pharmacology

Informations

• Publié par: S. Karger AG
• Date de parution: 14 juin 2022
• Nombre de lectures: 0
• EAN13: 9783318070873
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

ENHANZE Drug Delivery Technology
First published 2022
Text 2022 David W. Kang, Renee Tannenbaum
2022 in this edition S. Karger Publishers Ltd.
S. Karger Publishers Ltd., Elizabeth House, Queen Street, Abingdon, Oxford OX14 3LN, UK
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The rights of David W. Kang and Renee Tannenbaum to be identified as the authors of this work have been asserted in accordance with the Copyright, Designs Patents Act 1988 Sections 77 and 78.
The publisher and the authors have made every effort to ensure the accuracy of this book but cannot accept responsibility for any errors or omissions.
For all drugs, please consult the product labeling approved in your country for prescribing information.
Registered names, trademarks, etc., used in this book, even when not marked as such, are not to be considered unprotected by law.
A CIP record for this title is available from the British Library.
ISBN 978-3-318-07076-7
Kang DW (David W.)
ENHANZE Drug Delivery Technology/
David W. Kang, Renee Tannenbaum
Medical illustrations by Graeme Chambers, Belfast, UK
Typesetting by Amnet, Chennai, India
Printed in the UK with Xpedient Print
This work was funded by Halozyme Therapeutics, Inc., San Diego, CA, USA.
Preface
Acknowledgments
Introduction to subcutaneous drug delivery
Biology of hyaluronan and hyaluronidases in the subcutaneous space
History of hyaluronidases and development of rHuPH20
The ENHANZE platform: Clinical applications of a subcutaneous drug delivery technology
Application of ENHANZE drug delivery technology: Development of currently marketed products
Index
Preface
ENHANZE drug delivery technology: Advancing subcutaneous drug delivery using recombinant human hyaluronidase PH20 provides readers with in-depth information on the potential benefits and challenges of subcutaneous (SC) drug delivery, the biology of hyaluronan and hyaluronidases in the SC space, and a comprehensive overview on the history of hyaluronidases and the development of recombinant human hyaluronidase PH20 (rHuPH20). Current applications of rHuPH20 as well as approved biotherapeutics utilizing rHuPH20-facilitated SC drug delivery are summarized, and the underlying non-clinical and clinical development approaches are introduced as a basis for future application to biologics in various disease areas.
The ENHANZE drug delivery technology is based on the proprietary rHuPH20 enzyme, which facilitates and optimizes the SC delivery of co-administered therapeutics by locally depolymerizing hyaluronan in the SC space. This technology has been a step forward in high-dose and high-volume SC dosing of biotherapeutics. Traditionally, SC injection of larger volumes was conducted either by splitting the dose into several smaller-volume injections or by adhering to an appropriately slow infusion rate, thereby adding to the overall treatment burden for patients and caregivers.
Increasing dispersion of high-volume biotherapeutics following injection into the SC space by means of co-administration of rHuPH20 represents a way to help address some of the important challenges inherent to intravenous (IV) dosing. These challenges include the difficulty in establishing and maintaining peripheral IV access in some patients, and a typically high incidence of infusion-related reactions. Further, SC delivery may reduce the healthcare costs associated with IV administration, and it may also provide greater convenience for patients. The relatively short administration time when delivering high-volume therapeutics subcutaneously with rHuPH20 is often preferred by patients.
The use of rHuPH20 to facilitate the administration of immunoglobulins has reduced the dosing frequency in comparison with other SC formulations of immunoglobulins and permits home and patient self-administration. A possible future application of the technology could be to support the shift of high-dose biologic treatments from hospital-based IV administration to a home setting in other disease areas. In such a setting, patients and their lay caregivers could choose the time and place of drug administration based on individual preferences and capabilities. Shifting to a home administration setting may be particularly advantageous during times of increased risk, such as winter influenza seasons or times of global pandemic. Future applications of rHuPH20 have the potential to contribute to overall reduced dosing complexity and might omit the need for healthcare professional-assisted SC dosing for those treatments compatible with self-administration.
A variety of multidisciplinary stakeholders successfully collaborated in the development and application of rHuPH20. This included scientists in non-clinical pharmacology, pharmacokinetics, safety and technical development, clinical pharmacologists and medical scientists, as well as patients, their caregivers and healthcare professionals.
This book, together with the many references cited throughout its chapters, will be a valuable repository and guide for scientists, manufacturers and healthcare providers embarking into the field of SC delivery of high-dose biotherapeutics.
Beate Bittner, PhD
F. Hoffman-La Roche Ltd., Basel, Switzerland
Acknowledgments
Medical writing support, including assisting authors with the development of the outline and initial draft, incorporation of comments and fact checking, was provided by Kerry Acheson, PhD, Miriam Cohen, PhD, Rachel O Meara, PhD, and Talya Underwood, MSc; editorial support, including formatting and proofreading, was provided by Michelle Seddon, Dip Psych, all of Paragon, Knutsford, UK, supported by Halozyme Therapeutics, Inc., according to Good Publication Practice guidelines.
1 Introduction to subcutaneous drug delivery
Kenneth W. Locke and Daniel C. Maneval
Benefits and challenges of subcutaneous injection
Both enteral (gastrointestinal) and parenteral (non-gastrointestinal) delivery have been used for effective administration of therapeutic agents. Oral administration has historically been the choice for small-molecule drugs, but alternative administration routes have been developed to optimize delivery for biotherapeutics and drugs that have limited oral bioavailability. The most common parenteral routes include intravenous (IV), subcutaneous (SC), intramuscular (IM) and intradermal (ID) injection. SC injection involves inserting the needle into the fatty layer of the SC space (also known as the subcutis or hypodermis) just beneath the skin s surface ( Figure 1.1 ). The architecture of the SC space includes both capillary and lymphatic vessels (described in Chapter 2 ), and therapeutic agents injected into the SC space typically diffuse slowly with a sustained rate of absorption. 1 This makes SC delivery particularly effective for administering drugs that require continuous delivery at a low dose rate, such as insulin and pain medications. 1

Figure 1.1 Schematic of injection into the SC space. SC, subcutaneous.
The advantages of SC injection over IV administration include a simplified injection process, which removes the requirement for venous access, reducing the total administration time and enabling self-administration through more accessible injection sites. The SC route is, therefore, becoming a more common mode of delivery for monoclonal antibody therapeutics, including anti-cancer (e.g. rituximab and trastuzumab), anti-tumor necrosis factor (e.g. adalimumab and certolizumab pegol) and anti-immunoglobulin or anti-interleukin (e.g. omalizumab and mepolizumab) antibodies. 2 - 4 IV administration has a relatively high healthcare burden for both patients and healthcare professionals (HCPs), 5 - 9 and the specialized requirements for direct venous access may limit patient treatment with IV medications where there are insufficient administration centers or available trained operators. 9 , 10 In addition, IV administration may be more complicated for certain populations. Patients undergoing repeated treatments may be at risk of complications such as phlebitis, infiltration, extravasation and infections, 11 and establishing and maintaining peripheral IV access may be particularly challenging in patients with small or collapsed veins. 9 IV administration has also been identified as a source of medication errors such as incorrect doses and rates of administration, delays in administration, incorrect labeling procedures and patient identification errors. 12 These medication errors may be increased for some modes of IV administration, such as traditional gravity feed, compared with IV infusion devices. 12 In addition, IV administration of monoclonal antibodies has often been associated with a high incidence of infusion-related reactions. 13
SC drug delivery regimens may enable patient self-administration and HCP administration outside of the hospital setting. 5 , 14 Treating patients at home rather than in the hospital or infusion center setting has been shown to reduce costs, cause less disruption to activities of daily living and normal family life, and reduce stress to the patient. 15 - 17 In addition, home-based treatment provides patients with more involvement in their own healthcare, leading to greater independence. 16 Treatment at home can also increase scheduling flexibility, allowing administration at a time that does not impact on work or social life, and ultimately enabling improved adherence by avoiding missed doses. 15 - 18 In cases where treatments need to be monitored and administered in a hospital setting, SC adm