Orphan Drugs Return to Center Stage

Years of quiet success by the rare disease community have built to a moment where orphan drugs are once again at center stage. At the National Organization for Rare Disorders (NORD) policy summit last week, former FDA commissioner David Kessler led a blue-ribbon panel in front of an overflow crowd of more than 300. This past Wednesday, NIH launched a 5-year, $120 million program called Therapeutics for Rare and Neglected Diseases (TRND).

Four factors are driving this renaissance:

• Large unmet need. There are nearly 7000 rare diseases, but only about 200 have treatments. In the aggregate, between 25 and 30 million people in the US have a rare disease.
  
• Companies and Patients Have a Well-Defined Common Cause. In the area of rare diseases, patients cooperate, encourage and defend companies that develop and produce the medications they need. More patients may need high blood pressure medicines, but few of those patients care as dearly.
  
• Orphan drugs have been a central driver in the growth of biotechnology, a trend that may be accelerating. Orphan drugs come with incentives and can be profitable. New scientific knowledge in genomics and other cutting-edge technologies tend to favor well-characterized rare diseases.
  
• Challenges to orphan drug development, approval and marketing may be less than for drugs with more common indications. This increases the appeal of orphan drugs to large companies and may be a key to the survival for smaller companies.
  

While orphan drugs might seem favored, it is still a difficult path to an approved product. The purpose of the new NIH program is to get more promising orphan drug compounds through the expensive pre-clinical development process. Success rates during this phase are so low that it is often called "the valley of death" for start-up and small companies.

At the NORD summit, there was extended discussion of development, reimbursement and access issues. NIH's new program bears directly on drug development, while FDA enumerated a number of ways it assists companies and researchers. Some are mundane but necessary, such as more realistic requirements for the number of patients to be enrolled in trials. Other items represent serious re-thinking, such as a willingness to consider a disease's natural history as a control and openness to cross-over studies (i.e. each patient goes through drug and placebo stages and serves as their own control). A challenge given to NIH and FDA by the panel was to help characterize disease progression through research and patient registries.

Until recently, orphan drugs have tended to do better with payers than other expensive products because high costs are offset by low volumes. Nonetheless, no rare disease patient in the US can assume they will have access to the drugs they need. The British board overseeing UK coverage has demonstrated a willingness to deny access to care for cost reasons. Health care reform, follow-on biologics, comparative effectiveness and inequities between Medicare Part B and Part D are among the areas where rare disease patients and orphan drugs will have to find a path that works.

For readers interested in more information about orphan drugs, I recommend going to NORD's website, www.rarediseases.org, or the FDA website, www.fda.gov.

There is a free conference on June 4, hosted by the US Chamber of Commerce Foundation. Registration is required. http://ncf.uschamber.com/orphan_drugs/.

On July 15 and 16, there is a Rare Disease Leadership Summit in Arlington, Virginia. I will be presenting on "Personalized Medicine and the Future of Orphan Product Development." There is a fee for this one. More details are at: www.cbinet.com/raredisease.