By Kurt R. Karst –
On the first day of FDA’s two-day public hearing (agenda here) regarding the Agency’s regulation of drugs, biological products, and devices for the treatment, diagnosis, and/or management of rare (i.e., orphan) diseases, the National Organization for Rare Disorders (“NORD”) called for FDA to issue a Statement of Policy expressing a more granular expression of the Agency’s historic commitment to exercise flexibility in its review of therapies for rare disorders and for an FDA expression of ways to reduce regulatory uncertainty in the development and review of orphan disorder therapies.
NORD Board of Directors Chairman (and Hyman, Phelps & McNamara, P.C. Director) Frank J. Sasinowski stated during his testimony that FDA needs to “develop and issue a specific Statement of Policy on FDA’s role in regulating therapies for rare disorders, which includes an explanation and affirmation of the FDA’s historic position that FDA flexibly applies the standards of safety and effectiveness with respect to therapies for those with rare disorders.” Although FDA’s rigorous safety and efficacy standards apply equally to orphan drugs, “the FDA interpretation and application of those same standards have historically been tailored by FDA to the unique facts of each particular medicine under FDA review,” according to Mr. Sasinowski. Indeed, Mr. Sasinowski said that such a Statement of Poicy could stimulate orphan drug research: “the investment community and pharmaceutical industry may benefit from such a formal, explicit statement of policy that will encourage investment in, research of and development of medicines for those with rare disorders . . . for which there still is not a single FDA-approved therapy.”
NORD also commented on the need to increase regulatory certainty in the development of therapies for rare diseases/condition:
It is axiomatic that the perfect is the enemy of the good. In the world of rare disorders, there is much that is often not known or not known well, starting with the etiology and pathophysiology of the condition, including its natural history, and ranging to a lack of agreement among even a small handful of world experts on the most common clinical manifestations of some conditions. Against this backdrop, it is entirely understandable that FDA on occasion will find it difficult to concur in advance with a development program, even the design of a registrational trial under a special protocol assessment. However, researchers, industry and FDA, as well as most importantly, persons with the condition, may find that sometimes a study needs to proceed because patients are suffering and can not wait for the perfect trial design with the ideal primary endpoint to be eventually determined or developed and consensually accepted. . . . [W]hen these trials are conducted, sometimes with designs with which all parties may not be in full concurrence, including the FDA, great deference should be afforded the design of these trials and flexibility applied in the interpretation of their results.
Other recommendations were included in a presentation given by NORD Vice President Diane Edquist Dorman.
NORD’s stated need for greater certainty and predictability in the approval process was echoed in comments submitted to FDA by the Biotechnology Industry Organization, and will likely be stated again during the second day of FDA”s hearing.
The public hearing was held to assist FDA as the Agency implements § 740 of the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act of 2010 (Pub. L. No. 111-80), which, as we previously reported and as commented on by Office of Orphan Products Development (“OOPD”) Director Dr. Timothy Coté during his testimony at the hearing, requires FDA to convene a committee of expert Agency employees to consider the ways FDA reviews products to treat people with rare diseases, and consider policy improvements that might help people with rare diseases get better treatments faster. The public hearing is FDA’s first hearing on rare diseases since the Orphan Drug Act (“ODA”) was enacted 27 years ago. Since then, FDA has approved 350 products for rare diseases and has granted orphan drug designation for almost 2,200 products, according to OOPD’s database. Although the ODA has been hailed as a resounding success, there remain approximately 5,800 rare diseases/conditions for which there are no FDA-approved therapies.
Earlier this year, FDA announced the newly-created position of Associate Director for Rare Diseases in the Agency’s Center for Drug Evaluation and Research’s (“CDER’s”) Office of New Drugs. This orphan drug czar “will serve as CDER’s focal point to the rare disease drug development community and assist stakeholders and developers of drug and biologic products in navigating the complex regulatory requirements for bringing safe and effective treatments to patients in need.” In addition, OOPD recently introduced the Rare Disease Repurposing Database (“RDRD”), which is a listing of products that have received orphan designation and that are already approved for the treatment of some other disease. The RDRD is intended to push orphan drug research by providing sponsors with “a new tool for finding special opportunities to develop niche therapies that are already well-advanced through development.”