SCOPE OF THE WORKSHOP

In this context, the Institute of Medicine’s Forum on Drug Discovery, Development, and Translation held a public workshop on June 23, 2008, titled “Breakthrough Business Models: Drug Development for Rare and Neglected Diseases and Individualized Therapies.” The purpose of the workshop was to explore innovative strategies for orphan drug development. As outlined by workshop chair Nancy Sung,⁴ the workshop was designed to:

• provide an overview of how drug development is financed;
• review the state of orphan product development at FDA;
• explore new models for funding translational research and technologies; and
• examine and discuss the adequacy of the regulatory, legislative, and policy tools currently in place to help advance the development of drugs for rare and neglected diseases.

The workshop presentations and discussions considered a range of strategies for reducing the risk to industry and venture capitalists of investing in the development of such therapies by filling critical funding gaps along the drug development pathway and pursuing highly targeted approaches to early-phase development. Such strategies include sharing data and materials, managing intellectual property, launching clinical trials, and incorporating progress milestones. Speakers and participants examined the factors that contribute to successful approaches. They further discussed the use of these approaches by other organizations and in other disease areas in order to accelerate research on rare and neglected diseases. In addition, the workshop provided an opportunity for organizations with an interest in such diseases to share ideas and identify potential collaborative activities.

KEY THEMES

Over the course of the workshop several key themes emerged:

• Collaboration—Developing a drug for a rare or neglected disease is often prohibitive for any single organization. Establishing alliances is advantageous and can result in expanded access to innovative technology and to additional resources, including funding, intellectual property, disease experts, and patient communities. Several speakers stated that relationship building is paramount, and a successful relationship requires that knowledge and intellectual property rights flow in both directions to enable acceleration, innovation, translation, and deployment.
• Sustainability—The workshop discussions encompassed a broad spectrum of funding models, including philanthropy, pharmaceutical partnerships, venture capital, angel investors, and social investors, as well as product revenues and traditional sources such as loans, grants, and Cooperative Research and Development Agreements. Regardless of which models are pursued, the key to an organization’s long-term success and the success of its product pipeline is sustainability. Of the approaches discussed, those that had been in operation the longest used a diverse array of funding mechanisms to achieve sustainability.
• Sharing of data and materials—Making data and materials available and accessible is critical to progress. Establishing publically accessible repositories of tissue, nucleotide sequences, or clinical data for particular diseases is vitally important. These repositories facilitate sharing by requiring standardization of entries, validation of data, and the capability for direct input of data and samples by patients. Also important is the implementation of user agreements mandating that those accessing data or materials must share as well. Negotiations for sharing can be made more efficient through the use of standardized agreements.
• Global reach—When dealing with rare diseases affecting extremely small numbers of people, it is important to try to identify every patient afflicted worldwide. Doing so can make it possible to gather a large enough population for clinical trials and can also help determine the market for a product, aiding in the assessment of pricing and access.
• Communication with FDA—Drug sponsors have a legal right to meet with FDA regarding drugs in development. Early and frequent communication with FDA throughout the development process can increase the chances of a smooth, efficient process and a successful application. FDA can advise on trial planning and execution, such as the selection of appropriate end points for the indications desired.

ORGANIZATION OF THE REPORT

The chapters that follow summarize the presentations and discussions that took place during the workshop:

• Chapter 2 provides an overview of the current financial landscape at the various stages of drug development, including the investors at each stage, the drivers of investment for those funders, and the current state of investments.
• Chapter 3 reviews the regulations and opportunities that currently exist through FDA’s Orphan Drug Program, and describes strategies for accelerating the development of therapies for rare and neglected diseases.
• Chapter 4 is the first of four chapters offering specific examples of business models for the development of drugs for rare and neglected diseases. The funding models of four organizations are described: the Institute for OneWorld Health, a nonprofit pharmaceutical company; Cystic Fibrosis Foundation Therapeutics, a disease foundation that functions as a virtual drug company; Genzyme, a for-profit biotechnology company; and Celtic Therapeutics, a global private equity firm that functions as a virtual pharmaceutical company.
• Chapter 5 addresses strategies to facilitate the sharing of data and research materials. Two successful models are highlighted: the Alzheimer’s Disease Neuroimaging Initiative, a public–private partnership that is conducting a large observational longitudinal study of Alzheimer’s, and the Genetic Alliance BioBank, a centralized repository for disease-specific clinical data and biological samples, as well as medical records, DNA/RNA, self-reported patient information, cell lines, tissue, and organs.
• Chapter 6 provides examples of innovative ways in which intellectual property has been used to advance drug development for rare diseases. Examples discussed include pooling intellectual property, depositing it into a trust, allowing open access to data, implementing socially responsible licensing, standardizing material transfer agreements, and creating new benefit-sharing arrangements.
• Chapter 7 describes strategies for facilitating clinical trials. It reviews the regulatory tools available to assist with orphan drug development and approval processes, including fast track designation; accelerated approval; priority review; and early and frequent communication with FDA through such vehicles as Type A, B, or C formal meetings, special protocol assessments, or informal meetings.
• Chapter 8 outlines areas identified as needing further discussion: (1) business models for the development of drugs for rare and neglected diseases, as it is still too soon to be able to distill broadly applicable lessons and best practices, and new models will continue to be created; (2) the current state of data and resource sharing and public access, with a focus on distilling best practices; (3) intellectual property issues as they relate to orphan drugs and rare and neglected diseases; and (4) policies applied to the review of orphan drug applications, with consideration of what new or revised policies might better facilitate the approval of such drugs.
• Finally, a number of resources mentioned throughout the workshop are available on the Internet. Appendix C provides a list of web-sites for those interested in the development of drugs for rare and neglected diseases.

Footnotes

*

The planning committee’s role was limited to planning the workshop, and this summary was prepared by the workshop rapporteur and the Drug Forum staff as a factual summary of what occurred at the workshop.

1

For the purposes of this report, rare diseases are defined as diseases that affect small patient populations, and neglected diseases are defined as diseases that are concentrated in poor or developing countries.

2

The FDA Orphan Drug Program is discussed further in Chapter 3.

3

Therapies for rare and neglected diseases may be designated as orphan products if one of the following conditions is met: (1) the disease or condition for which the drug is intended affects fewer than 200,000 people in the United States or, if the drug is a vaccine, diagnostic drug, or preventive drug, the persons to whom the drug will be administered in the United States are fewer than 200,000 per year as specified in 21 CFR § 316.21(b); or (2) for a drug intended for diseases or conditions affecting 200,000 or more people, or for a vaccine, diagnostic drug, or preventive drug to be administered to 200,000 or more persons per year in the United States, there is no reasonable expectation that costs of research and development of the drug for the indication can be recovered by sales of the drug in the United States as specified in 21 CFR § 316.21(c).

4

Nancy Sung, Ph.D., is a Senior Program Officer for the Burroughs Wellcome Fund.