Developing Orphan Drugs: Part 1 Pursuing the Orphan Designation

I am pleased to announce the return of one of our guest bloggers: Sam Bell. Sam will be following this post with “Orphan Drugs: Part 2.”

Should you consider pursuing an orphan drug designation for one of your NMEs or previously-approved products? In a word, yes – you should seriously explore whether each molecule in your pipeline could qualify in one or more indications.

Orphan status can not only help speed the creation of new drugs for patients in need, but also deliver substantial benefits for sponsors, including:

  • fast-track status
  • priority review
  • accelerated approval
  • seven years of market exclusivity
  • tax breaks
  • FDA assistance with protocol development and regulatory flexibility.

Furthermore, rules allow multiple orphan designations for a single drug that can progressively expand its potential market. Novartis’ Gleevec received seven different orphan designations that led to nine different marketing indication approvals between 2001 and 2013, greatly expanding its potential market and extending exclusivity for at least one indication to 2020.

The Orphan Drug Act also encourages repurposing of previously approved drugs as orphan drugs for new indications. There are incentives for conducting new research on approved drugs to provide evidence of efficacy in treating rare diseases. The brand-name identities of some orphan drugs may surprise you. In 2011, sildenafil received orphan designation (but not yet marketing approval) as a treatment for pediatric pulmonary arterial hypertension. You’ve probably already heard of sildenafil as the blockbuster ED treatment called Viagra.

The repurposing of sildenafil shows that even a drug previously approved for a common indication can receive orphan designation for a different indication that qualifies as an orphan disease. Furthermore, it is possible to receive market exclusivity for an off-patent drug for orphan indications. The FDA has given orphan designation to over 100 drugs with existing approvals for more common diseases. The FDA provides a database with information on repurposing of existing drugs for rare indications.

From Blockbusters to Orphans

This year marks the 30th Anniversary of the Orphan Drug Act. The Act has been highly successful in its goal of stimulating development of treatments for rare diseases. Indeed, pursuit of the orphan designation resembles a gold rush. Since 1983, the FDA has granted orphan designation to more than 2800 drugs and given marketing approval to over 430 of them. The number of yearly orphan drug designations increased from 70 in 2000 to 190 in 2012, with more than half of all orphan drug designations granted since 2004.

The number of approvals of orphan drugs also continues to grow, increasing from 13 in 2000 to 25 in 2012. The orphan path has become particularly attractive for new molecular entities (NMEs), as high costs and low success rates have discouraged pursuit of new “blockbuster” drugs with broad target populations. In 2000, about 7% of NMEs approved for the U.S. market had orphan status. By 2011, that percentage had more than quadrupled to 29%. Counting new orphan indications for previously approved drugs, orphan drugs make up an even higher percentage of overall marketing approvals. Dr. Timothy Coté, the former director of the FDA Office of Orphan Products Development, said in a recent interview that orphan drugs “now represent about 40% of everything the FDA approves.”

The exclusivity that comes with orphan approval, combined with the small size of the market, can also lead to high prices that increase the chance of generating a profit. However, there are emerging signs of price resistance that bear watching as you assess market potential for a drug with an orphan designation. In assessing market potential, also remember that different countries and regions define orphan drugs differently. In the United States, the designation requires targeting a disease that either affects less than 200,000 people or otherwise does not have a “reasonable expectation” that sales would cover development costs. In the European Union, the orphan designation requires targeting a disease that is not only uncommon and potentially unprofitable but also life threatening or chronically debilitating.

Can Your Drug Qualify as an Orphan?

Is your drug an orphan, or a candidate to become one? The potential benefits of the orphan designation justify exploring each of the several ways of qualifying a molecule. A drug with orphan status in several indications may resemble the blockbusters of yesteryear.

The FDA’s Office of Orphan Products Development (OOPD) provides information on regulations and the drugs and diseases that have previously received the orphan designation. Orphanet, led by an international consortium with support from the European Commission, has created extensive databases and other resources on rare diseases. Re-examining everything you know about your molecules in the light of the information you find in these resources may open new possibilities for your development program.

Next Week: How Orphan Drug Designation Affects Investigational Plans and Trial Designs

The orphan designation can clearly be an attractive pathway to market for many drugs. Next week in Part 2 of this look at orphan drugs, I’ll discuss some of the ways that the Orphan Drug Designation affects investigational plans and clinical trial designs.

Sam has worked in clinical drug and device research for two decades in a wide range of therapeutic areas, including four years as a project manager. He is currently the lead medical writer at Health Decisions. Sam has served as primary author of five Clinical Study Reports, has overseen preparation of two initial IND submissions and has served as lead or co-author on numerous protocols, Investigator’s Brochures and IND Annual Reports. Sam holds degrees from Vassar College and the University of North Carolina at Chapel Hill.  


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