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This post was written during early stages of trying to understand a complex scientific problem, and we didn't get everything right. The original author no longer endorses the content of this post. It is being left online for historical reasons, but read at your own risk.

Orphan drug (from Wikipedia):

An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease. The assignment of orphan status to a disease and to any drugs developed to treat it is a matter of public policy in many countries, and has resulted in medical breakthroughs that may not have otherwise been achieved due to the economics of drug research and development. In the US and EU it is easier to gain marketing approval for an orphan drug, and there may be other financial incentives such as extended exclusivity periods.

The Orphan Drug Act (ODA) of January 1983, passed in the United States, with lobbying from the National Organization for Rare Disorders and many other organizations,[1] is meant to encourage pharmaceutical companies to develop drugs for diseases that have a small market. Under the law, companies that develop such a drug (a drug for a disorder affecting fewer than 200,000 people in the United States) may sell it without competition for seven years,[2] and may get clinical trial tax incentives.[2]

Orphan drug designation means that the sponsor qualifies for certain benefits, such as reduced taxes, from the federal government.

Orphan drug developers:

Regulus Therapeutics:

Orphan Europe:

Orphan drug à Industry Involvement (from Wikipedia):

Key orphan drug developers including Synageva BioPharma Corp., Swedish Orphan Biovitrum, Shire plc, GlaxoSmithKline, Pfizer, Novartis, Genzyme, Lundbeck and BioMarin are leading the way in this growing industry. These pharmaceutical companies work together with national bodies such as the U.S.’s National Organization for Rare Disorders (NORD) and the European Organization for Rare Diseases (EURORDIS) to advance this field.


National Organization for Rare Diseases:


“While advocacy abounds, orphan drug development success remains elusive,” Philippidis, Genetic Engineering and Biotechnology News (2011)

Perhaps, however, the brightest hope for aiding orphan drug development rests with the budget for the coming fiscal year, which starts October 1. The $3.8 trillion budget proposed by President Obama includes the creation within NIH of a new institute designed to promote translational medicine. The National Center for Advancing Translational Sciences (NCATS) would concentrate in one place $700 million allocated for existing NIH units scattered across the agency, including the Office of Rare Diseases Research.

Christopher P. Austin, M.D., senior advisor to the director for translational research at NIH, described NCATS’ strategy for orphan diseases as orthogonal. “The center will look at the similarities in 1000s of rare diseases and look at therapeutic approaches that may affect multiple of them simultaneously, instead of going down the traditional route, which is to pick a disease, pick an approach, and then push very hard on that one very narrow approach.”

NCATS would oversee the Therapeutics for Rare and Neglected Diseases (TRND) program, a $24 million NIH initiative launched in 2009 to stimulate collaborations with academic scientists. Dr. Austin said TRND currently has five pilot projects, with plans to ramp up to 10 projects at various stages of preclinical research.

NIH Director Francis S. Collins, M.D., Ph.D., said he hoped to open NCATS on October 1. That assumes lawmakers will have approved a budget by then, a risky supposition at best given that Congress is already sharply split on various issues.

Until the budget became a major issue, Washington had been ramping up spending for rare diseases. In addition to launching TRND, NIH expanded its Rare Diseases Clinical Research Network in 2009. It spent just over $117 million over five years to fund 19 research consortia and a Data Management Coordinating Center, with the goal of studying the natural history, epidemiology, diagnosis, and treatment of more than 95 rare diseases.

NIH and FDA Initiatives

NIH and FDA also came together in asking the Institute of Medicine of the National Academies to study the opportunities and obstacles for developing treatments for orphan diseases. The resulting report “Rare Diseases and Orphan Products: Accelerating Research and Development,” issued last year, called for an “integrated national strategy to accelerate research and product development for rare diseases” as well as several specific action recommendations:

  • NIH should develop a comprehensive action plan for rare disease research that would cover research program planning, grant review, training, and coordination of all phases of research.
  • NIH should increase its capacity and flexibility to support all phases of clinical research related to rare diseases, including clinical trials of new and repurposed therapeutic agents.
  • FDA should expand its Critical Path Initiative to define criteria for the evaluation of surrogate endpoints for use in trials of products for rare conditions.
  • FDA’s Center for Drug Evaluation and Research (CDER) should evaluate the extent to which studies submitted in support of orphan drugs are consistent with advances in the science of small clinical trials and associated analytic methods.

“It’s fair to say that this whole effort in rare diseases and orphan diseases is dramatically under-resourced, underfunded, and uncoordinated,” Dr. Austin said. “To have the National Academies say that is the case was very helpful, frankly. In an environment of tough competition for budgets, it helps to have the National Academy come out and say, ‘We think this is a very important problem, and here’s what you ought to do to help solve it.’”

Dr. Groft cautioned, however, that the report’s findings are unlikely to be carried out quickly: “Many of these recommendations are just not things you can accomplish within six months or nine months, but they do take years both of planning and then of implementation.”

NIH and FDA are in their third year of co-sponsoring a course in the design of small clinical trials. The joint activity has proven valuable, Dr. Groft said, by shedding light on the sheer complexity of studying rare diseases, which requires researchers from NIH’s numerous institutes to develop therapies by working together and building partnerships with patient advocates and industry.

FDA early last year created a new associate director for rare diseases position within CDER’s Office of New Drugs that would be “a focal point for the rare disease drug development community” by helping drug and biologic developers and others with a stake in creating orphan drugs navigate the agency’s complex regulatory requirements.”

Also last year, FDA launched the Rare Disease Repurposing Database, listing products that have received orphan status designation and are already market-approved for the treatment of some other diseases.

“It’s going slowly, but it’s going forward,” Dr. Coté told GEN. He said FDA has spoken to “a number of” prospective sponsors interested in supporting the repurposing of drugs for orphan diseases,” but couldn’t disclose details.

The emergence of those sponsors, along with new laws, continued partnership-building, increased advocacy, and NIH-FDA initiatives are all likely to help people with orphan diseases find the treatments they need. But like the FDA database, while progress may be indeed going forward, it’s also going slowly.