FDA and Rare Disease Drug Development, from FDA Week

June 29, 2010 // [FDA Week, http://insidehealthpolicy.com/]

FDA is currently in the middle of a flurry of activity aimed at better focusing its regulation of rare disease treatments, but the agency disappointed some outside advocates by delaying the possibility of creating a special rare disease review division within FDA for at least a year. That news came to advocates from FDA staffers an hour before a Senate Appropriations subcommittee looking at federal regulation of these diseases last Wednesday (June 23), a source said. More surprising to the source were comments from National Organization for Rare Disorders leadership during the hearing that the establishment of the new agency division would be a mistake.

FDA has two working groups addressing the issue and a number of rare disease regulatory advocates are proposing improvements to the agency’s regulatory regime. Senate appropriators are also eying whether legislation is needed.

The concept of a rare disease review division has been championed by the Emil Kakkis and his foundation, which has long advocated for Congress to provide FDA $10 million to create the special division. Kakkis and other rare-disease treatment advocates argue that gathering FDA’s experts in the field into one group would help accelerate the regulatory process.

The move would have an “immediate impact on new treatments” and would signal to the biotechnology industry that the agency was “serious” about this effort, Kakkis told the Senate FDA appropriations subcommittee. A special division would encourage more investment and allow for products already in the pipeline to be more quickly acted on, Kakkis said.

FDA should “have a division that has particularly trained people in the diseases that are both chemical, muscular or some of the other genetic rare disorders that take specialized expertise,” Kakkis told the subcommittee. The best regulation would come from consolidating FDA’s experts who are “scattered throughout” the agency, adding staff and building a division where staffers can avoid “having their expertise diffused and not leveraged over time,” Kakkis said.

The problem without a dedicated division also comes with a lack of centralized responsibility for reviewers, Kakkis added. “There are definitely people [in FDA] with expertise who can review these, but often they are called on to do other tasks,” Kakkis said. “This is a way to get better decision-making.”

But a Kakkis foundation staffer told FDA Week that meetings between advocates and FDA staffers prior to the hearing indicated that, while conceptually supportive of the idea of specialization, the timing did not work for the division to be created this year. That impression became formal an hour before the hearing.

The source said his reading of the situation was that FDA was possibly waiting until after drug user fees are reauthorized in 2012 to create the office.

The “biggest shock” from the day, the source said, came from Diane Dorman, the National Organization for Rare Disorders’ vice president for public policy, who said NORD flat-out disagreed with the concept. Dorman said NORD was “somewhat concerned” because of the worry that a separate division would create “narrow silos” within FDA.

By way of example, Dorman described the National Institutes of Health’s office on rare diseases as a nimble group with which the office’s director can leverage opportunities across all NIH offices and institutes without barriers. There’s a possibility to create an ad hoc group, “but creating an additional silo [within FDA] in our opinion may cause problems to access,” Dorman told the subcommittee.

In his response, Kakkis said without the review division FDA “cannot alter the review process for drugs in a way that is fundamental.” Creation of the division would let staffers be “personally responsible to make decisions,” he added.

“I think you’d want your drugs to be reviewed by people who are trained in the area, that specialized in it, and really understand it,” Kakkis said.

FDA Deputy Commissioner for Science and Public Health Jesse Goodman said the agency is aggressively addressing orphan drug issues, pointing to two new expert working groups FDA established in March, the Rare Disease Review Group and the Neglected Disease Review Group.

Those workgroups “will look at all the ideas we’ve heard here” before issuing a report to Congress, Goodman said. The two groups were created to help implement language in the FY 2010 Appropriation Act, which directed FDA to establish the internal review groups to address rare and neglected diseases, and to report to Congress one year after establishing the groups before issuing guidance.

That language came at a request from Sen. Sam Brownback (R-KS), the ranking member on the subcommittee.

Other work recently undertaken by FDA include the agency’s Office of Orphan Products Development starting use of a new tool, the Rare Disease Repurposing Database, which identifies drugs deemed promising for rare illnesses and are already approved by FDA for another disease (see related story).

A “novel feature and major advantage of this database” is its focus on drugs that have already gone through the FDA approval process, Goodman noted in its written testimony. “Thus, repurposing of these drugs for a new rare disease indication might be attainable quickly, relatively inexpensively, and at great benefit to the patients involved.”

In February, FDA created a position of associate director for rare diseases in the Center for Drug Evaluation and Research, which serves as the center’s focal point to the orphan drug development community “in navigating the complex regulatory requirements for bringing safe and effective treatments to patients,” Goodman wrote.

The agency is also collaborating with other entities to help ramp up its rare-disease treatment efforts.

In October 2010, FDA will co-sponsor its first rare disease investigator training course, in collaboration with NORD and NIH. FDA is also planning a series of scientific workshops to address difficult rare disease research issues. And FDA and NIH are co-sponsoring an Institute of Medicine study to review national policy for rare disease research and related medical product regulation, with recommendations due this September.

Experts suggest that there are roughly 200 FDA-approved treatments for the nearly 7,000 rare diseases that exist globally. So “while there have been many successes, the unmet needs are huge,” Goodman told the subcommittee. Rare diseases are defined as diseases affecting fewer than 200,000 people in the United States.

The FDA estimates that a billion people worldwide are affected by at least one neglected disease like tuberculosis, malaria and leprosy.

These issues are FDA’s concern because “infectious diseases know no boundaries,” Goodman said. “Threats to health anywhere are threats to everyone.”

The agency also is preparing for public hearings on June 29-30 focusing on how it approves and encourages medical products for rare diseases. — Seth Freedland (sfreedland@iwpnews.com)