Orphan Drugs

Understanding the Rare Disease Market and its Dynamics

Elizabeth Hernberg-Ståhl, Miroslav Reljanović

• Publisher: Woodhead Publishing
• Year: 2013
• Print ISBN: 9781907568091
• eBook ISBN: 9781908818393
• Topic: Medicine
• Subtopic: Infectious Diseases

This authoritative and comprehensive book makes the reader familiar with the processes of bringing orphan drugs to the global market. There are between 5, 000 and 7, 000 rare diseases and the number of patients suffering from them is estimated to be more than 50 million in the US and Europe. Before the orphan drug legislation enacted in the US in 1983, there was a limited interest from industry to develop treatment for very small patient groups. One of the difficulties is, of course, that similar levels of investment are needed from a pharmaceutical company to bring a drug to the market for both small and large patient groups.The journey from application of an orphan drug designation to a reimbursed market- approved drug is long and many obstacles occur during the journey.After reading the book, readers will: Understand who the players/stakeholders are in the rare orphan disease field and their specific needs and concerns: patients and patient organizations, researchers and treating physicians within the field, industry, regulatory and reimbursement bodies* Understand the strong partnership between the different players and the various initiatives to improve and increase access to treatment for patients; minimizing the gap between numbers of known diseases, orphan designations, approved drugs and paid drugs.The book also provides short practical case stories from patients and researchers, as well as representatives from industry and authorities on the challenges they came across in developing orphan drugs or getting access to orphan drugs.- A comprehensive overview of strategy, key activities and considerations of how to bring an orphan drug from concept to the market and make it available to patients- A source of updated information, news and trends for those who are already active in this fast-evolving field- Covers the global definitions and the criteria for getting an orphan drug designation in, for example, the US and Europe

Introduction

Patients suffering from rare diseases were not well served until the US Orphan Drug Act (ODA) of 1983 was put in place to stimulate and motivate the worldwide pharmaceutical and biotechnology industry to develop treatments for this patient group. The main rationale and cornerstone of this regulation from its inception was to put the rare disease patient at the centre of all activities and to ensure that they have the same access to medical treatments as patients with any other disease.

Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including … medical care. …

(Universal Declaration of Human Rights, United Nations 1948)

Before these regulations and incentives for the industry were put in place only a handful of drugs were approved for patients with rare diseases. A drug under development may be granted orphan drug status under this legislation if it meets certain criteria in a formal application process. In order to be eligible for orphan drug designation (ODD), the intended target indication must satisfy specific orphan disease criteria such as rarity. The indication will also be evaluated for medical plausibility and to determine whether the new drug has the potential to provide significant benefit to the affected patients. If the drug is assigned orphan drug status, further support is available during clinical development through incentives provided in the legislation, together with a potential reduction in the manufacturer’s financial risk as a result of the defined period of market exclusivity following marketing authorisation.

Orphan drug legislation has been in place since 1983 in the USA and since 2000 in Europe. It is an important and successful legal framework that has motivated the pharmaceutical industry to invest in the development of new treatments for formerly neglected diseases.

Indeed, the success of the orphan drug legislation (together with the incentives that are associated with it) is underlined by the steady increase in the number of designations for orphan designation seen in Europe: 107 designations were granted in 2011, 148 in 2012 and more than 150 are expected in 2013. In-line with this trend, in 2012, 19 applications for marketing authorisation concerned designated orphan medicines, compared with 14 in 2011.

Table 0.1 gives a more complete picture.

Table 0.1

Overview for orphan medicinal product designation procedure since 2000

²Negative opinion adopted in 2009 was revised and finalised in 2010, therefore it is not included in 2009 listing.

³Following a quality assurance exercise it was identified that this figure needed correction.

Source: Taken from EMA/C0MP/63660/2013

A similar picture is seen in the USA, where there were 2730 designations for orphan drugs, and 421 approvals up to 31 December 2012.

More information on orphan drug designation and approvals in the USA can be found at: www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm

However, despite the large number of orphan drug designations, from looking at the data above and from the data in Table 0.1, it can also be seen that while many drugs have received regulatory approval, many of the designated products failed during the course of development, and never reached the market. As with non-orphan drugs, there is no information available for most of these orphan drugs as to why they failed early in development. Despite numerous approved new medicines for rare diseases, most of the patients affected by the 5000 to 8000 rare diseases still remain without cure or treatment. There is ongoing huge, unmet medical need to improve the lives of these patients with fatal and disabling conditions.

Most companies dedicated to development of orphan drugs are small and middle sized companies. However, in the last few years several big pharmaceutical companies have entered the field. This gives hope that a new wave of orphan drugs may become available over the next years, as it is possible that at least some of the lack of progress in orphan dug development might have been caused by limited resources or financial shortcomings.

Unfortunately there are many misconceptions around the orphan drug legislation. It has been seen as a shortcut to faster market access for drugs with a high price and long-lasting exclusivity. Some of the misinterpretations of the current orphan drug legislation are:

a higher probability of regulatory approval;

smaller trial sizes result in lower overall development costs;

less clinical development time on average;

less regulatory review time on average;

once approved for marketing the orphan drug will be highly profitable;

the orphan drug market is generally less price sensitive.

These misunderstandings may increase the risk of an unwillingness to reimburse such medicines by public payers and a negative impact on the access to new innovative drugs for the affected patients.

This book attempts to provide some help in understanding the original goal of orphan drug incentives, why they are important for the patient and what problems a pharmaceutical manufacturer may encounter to bring them to market. It is a first introduction to the world of rare diseases and orphan drugs. The book is intended to be a companion for the journey from the application of an orphan drug designation to a reimbursed market-approved drug.

After reading the text, the reader will better understand:

what an orphan designation means around the world, as there is no one single international definition;

what the main steps involved in orphan drug development are and where to find more in-depth information;

what a rare disease is beyond prevalence figures, and what broad spectrum of diseases are summarised under the definition;

what role patient advocacy groups, as a major stakeholder, or patients have in the direct support of orphan drug development or in driving policy questions related to impr...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of figures and tables
• Acknowledgements
• About the authors
• Chapter 1: Introduction
• Chapter 2: Orphan drugs and orphan drug legislation
• Chapter 3: Characteristics of rare diseases
• Chapter 4: Patient network and advocacy groups
• Chapter 5: Organisations and networks dedicated to rare diseases and orphan drugs
• Chapter 6: Policies and research funding
• Chapter 7: Designing robust clinical trials for orphan drugs
• Chapter 8: Market access procedures for orphan drugs
• Index