Developing an Orphan Drug? Understand the FDA Guidance

FDA guidance for rare diseases

Developing an Orphan Drug? Understand the FDA Guidance

By definition, a rare disease affects less than 200,000 Americans.1 Currently, there exists an estimated 5000-8000 rare diseases affecting more than 25 million Americans.2 The lack of adequate understanding of the pathophysiology and clinical signs and symptoms of the diseases often results in delayed or missed diagnosis. Most rare diseases have yet to have an effective treatment option. In the United States , drug development for rare disease has taken giant leaps in the past few decades since the passage of the Orphan Drug Act in 1983.  With the incentives offered as a result of the Act, such as tax credits of 50% of clinical trial costs, waiver of user fees and seven year marketing exclusivity, the number of medicinal products approved for the treatment of rare disease has grown significantly.3 To date, more than 500 medicinal products have been approved in the US for the treatment of rare diseases compared to less than 60 products approved within the first 10 years of the inception of the Act.4

Pharmaceutical and biotech sponsors still face hurdles when seeking FDA approval of new medications for rare diseases. UBC examined the FDA’s draft guidance related to the development of these drugs and presented the results in a poster at ISPOR titled “Applications of the FDA Guidance on Common Issues in Drug Development on Rare Diseases”.

Regulatory Guidance

In August 2015, the United States Food and Drug Administration (FDA) released a draft document to address common challenges in developing drugs for rare diseases.  The following important aspects were outlined in the Guidance Document (U. S. Food and Drug Administration, 2015, p. 1-2):5

  • Adequate description and understanding of the disease’s natural history
  • Adequate understanding of the pathophysiology of the disease and the drug’s proposed mechanism of action
  • Nonclinical pharmacotoxicology considerations to support the proposed clinical investigation or investigations
  • Reliable endpoints and outcome assessment
  • Standard of evidence to establish safety and effectiveness

Practical Considerations

Reflecting upon these issues as early as possible will prepare a product’s sponsor to react quickly to both foreseen and unexpected challenges during the course of drug development, as well as seizing the opportunity to make a head start on research activities that may bring efficiencies for postmarketing surveillance efforts.

Next week I’m joining health professionals in Dublin to discuss advancements in pharmacoepidemiology at ICPE’s annual meeting. I’ll present a related abstract looking at the orphan drug regulations in the EU:

Impact of the EU orphan drug regulation on the development of orphan drug: a 15-year analysis
11:45 a.m. - 12:45 p.m., 27 August, Session# 91; poster #680 (Poster Session B – Potpourri)

UBC’s team of scientific advisors has provided clinical development and late stage services for more than 35 rare disease projects, touching more than 8,900 subjects and 1,500 sites. From consulting to implementation, our team can chart the course for your orphan product. Stop by booth 31 at ICPE, contact us or click here to learn more.

1Public Law 97-414, 96 Stat. 2049 (1983). Amended by Public Law 98-551 (1984) to add a numeric prevalence threshold to the definition of rare diseases.
2Rare diseases clinical research network. National Institutes of Health website. Updated March 29, 2013. Accessed April 25, 2016.
3Reese JH. FDA orphan drug designation 101. European Medicines Agency website. March 10, 2014. Accessed April 25, 2016.
4Impact of the orphan drug tax credit on treatmen6ts for rare diseases. Biotechnology Innovation Organization website. Published June 2015. Accessed April 25, 2016.
5U. S. Food and Drug Administration/Office of New Drugs and the Office of Translational Sciences of the Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) (2015). Rare Diseases: Common Issues in Drug Development Guidance for Industry. Silver Spring, MD: Author.