At present many orphan diseases do not have any licensed treatments, and for those conditions where there is a therapy, it is often the only therapy in the class that is available. However, this is not always the case. In the field of blood-plasma proteins, therapies to treat hemophilia, alpha-1 deficiency and primary immune deficiencies have multiple innovator versions in a therapeutic class. Often one product in the class has received an orphan designation and is exempt from the annual pharmaceutical fee, user fees and 340 B expansion, while the other versions in the class are not exempt.
Patients with rare medical disorders have benefitted from the Orphan Drug Act of 1983, a catalyst for many companies to pursue orphan product development that otherwise may not have occurred. For first-to-market products or originator therapies, the ODA functions as originally intended by promoting product development with incentives to companies that develop therapies. However, a problem occurs when some subsequent products try to achieve orphan designation, which is a disincentive to developing important rare disease therapies.
Current regulatory interpretation states that in order for subsequent products to be designated as orphan drugs they must first be proven “clinically superior” to the originator product thus linking the orphan designation to clinical superiority. Having to prove superiority to obtain designation is not only inconsistent with ODA, it’s costly, time consuming, and often not feasible.
A regulatory revision of “delinking” orphan designation from clinical superiority has recently been proposed. This would allow orphan designation to occur as long as the product meets all other criteria in the statute. Importantly, the proposal to delink orphan designation from clinical superiority would in no way undermine exclusivity. A similar orphan designated product could not be marketed for an indication for which another product has exclusivity. The first orphan designated product to achieve exclusivity deserves it. However, these subsequent products are in every way orphan therapies and important alternatives for treatment. They provide additional supply security for patients and physicians, an important fact given the great concern about supplies of critical therapies in the public arena.
This situation can be rectified, consistent with the statute, by allowing orphan designation to occur without having to demonstrate superiority. With this change, subsequent therapies would not be discouraged and unnecessary resources would not be expended to achieve superiority in order to get the designation, if that is even achievable for the product candidate in question. Toward this end, organizations such as BIO, PhRMA and PPTA provided written comments supporting this recommended change last year when the FDA offered their proposed rule on updating the orphan drug regulations.
The following is an excerpt from comments submitted to the FDA on January 17, 2012 by Andrew J. Emmett, BIO’s Managing Director, Science and Regulatory Affairs:
“…We urge FDA to reevaluate its misinterpretation of the clinical superiority requirement and eliminate the requirement for orphan designation, while maintaining the requirement for orphan approval/ exclusivity, as necessary. This protects the value of orphan exclusivity and advances the overall intent of the Orphan Drug Act to stimulate development of rare disease therapies.”
Dennis Jackman is Senior Vice President for Public Affairs at CSL Behring.