The search for orphans
ODA gave FDA the job of defining orphan diseases and proposed treatments. In 1983, we knew there were many rare diseases,
but "we were clueless" about the scope of the problem, recalled Marlene Haffner, former head of FDA's OD office. The emergence
of AIDS, which was then an orphan disease, put the program on the map.
During the past 25 years, FDA's Office of Orphan Products Development (OOPD) has received 2622 requests for OD designation
and has awarded that status to 1850 products. Of those, 326 ODs have been approved, and 41 of those approvals were supported
by FDA grants. More than three-fourths of approved orphans are conventional drugs, but approvals are now shifting toward biologics,
noted OOPD Associate Director Debra Lewis.
OD designation carries important benefits such as a 50% tax credit for clinical-research expenses. The credit can apply to
past taxes or be carried forward for as long as 20 years. Designated orphan products also are exempt from the user fee for
filing a new drug application (NDA), which is currently more than $1 million.
A designation application should be brief, says OOPD Director Timothy Cote. It should provide a scientific rationale that
is consistent with accepted medical knowledge and demonstrate how the test treatment will be used to treat a rare condition.
The application also must provide disease-prevalence criteria to document that the drug will treat a population smaller than
200,000 US patients. FDA recognizes that it must provide more clarity and guidance to applicants and make the designation
process more efficient. The European Union processes 90% of designation applications in 60 days, while FDA processes 40% in
60 days. "We can do better than that," Cote said.
In Washington This Month
OOPD also provides grants for orphan-product development and assists sponsors in designing research protocols that will meet
FDA requirements. FDA has awarded more than 400 grants (of 1500 applications), which generally amount to $400,000 per year
for four years. OOPD makes about 15–20 new grants each year and has about 70 active grants at any one time.
Another OOPD assignment is to identify medical devices that qualify under "humanitarian use" provisions to encourage the development
of medical devices to treat rare conditions. Products for conditions affecting fewer than 4000 Americans may receive FDA approval
if they demonstrate safety and "probable benefit." These criteria are less burdensome than documenting full effectiveness.
This process may become more important to pharmaceutical companies as more combination products emerge, Lewis commented.
In addition to spurring OD development in the US, ODA has inspired similar strategies around the world, Cote commented at
the 2008 meeting of the International Conference on Rare Diseases and Orphan Drugs (ICORD), which also took place in Washington
in May. The many participants from foreign regulatory agencies, research organizations, and pharmaceutical companies supported
international collaboration and investment in rare-disease research, particularly on the many third-world diseases that are
orphan conditions in the US and EU.
The EU adopted an OD program in 2000, which has resulted in 28 product approvals. Now FDA and the European Medicines Agency
(EMEA) seek to spur OD development by harmonizing the relevant regulatory processes. The two authorities have developed a
common application for industry to seek OD designation, a process that was achieved in a record six months. Both regions already
had similar approaches, as seen in data showing that FDA and EMEA granted OD designations in 90% of applications from 2000
to 2005, pointed out Yann Le Cam, CEO of the European Organization for Rare Diseases, at the DIA conference. Harmonization
also was spurred by mutual political support for "trans-Atlantic administrative simplification" strategies, said Kerstin Westermark,
chair of EMEA's Committee for Orphan Medicinal Products.
Since the common format was adopted in November 2007, FDA has received 16 OD requests on the new application, and EMEA has
received six. The numbers are disappointing, but the cooperative effort should be regarded as the "first stone that will pave
the road towards a global orphan-drug approval process," said Caterina Edfjall of Celgene (Summit, NJ) at the ICORD meeting.
Push for tropical disease treatments