If the FDA has its way, other drugmakers won't benefit from a recent federal court decision ordering the agency to grant Depomed Inc. orphan drug exclusivity for its postherpetic neuralgia (PHN) drug Gralise.

In an attempt to clear up any uncertainty created by the district court's September decision, the agency said while it has granted the exclusivity to Gralise (gabapentin), it will continue to follow a policy that limits the seven-year exclusivity to novel drugs approved for orphan indications or those that demonstrate clinical superiority to an older iteration of the drug approved for the same orphan use.

In a clarification scheduled for publication in Tuesday's Federal Register, the FDA cited the narrowness of the court decision in Depomed Inc. v. HHS as justification for standing its ground with other drugmakers.

The FDA's policy draws a broad, bright line between orphan designation and exclusivity.

Whereas a plausible hypothesis of superiority is good enough to get orphan drug designation, that hypothesis must be proved to obtain exclusivity. Superiority may be measured in terms of safety, efficacy or major contributions to patient care, such as a change that improves administration.

Thus, the sponsor of a designated candidate that has the same moiety and orphan indication as a previously approved drug must demonstrate, upon approval, that its product is clinically superior to the older drug to be eligible for orphan exclusivity.

Gabapentin was first approved in 1993 in capsule form as Neurontin (Pfizer Inc.) to treat PHN and epilepsy. The FDA granted the tablet formulation of Gralise, a once-daily dosage of 1,800 mg, orphan designation for PHN in November 2010, but when the agency approved the drug two months later, it refused to award it exclusivity. (See BioWorld Today, April 8, 2011.)

In denying the exclusivity, the agency determined that Gralise was the same drug as Neurontin, because it contained the same active moiety, was approved for the same orphan use and did not demonstrate clinical superiority to Neurontin.

Claiming the FDA's action was inconsistent with the Orphan Drug Amendments and the agency's own regulations, the Menlo Park, Calif.-based Depomed filed suit to force the issue in 2012.

That same year, the FDA retroactively revoked orphan exclusivity for Octapharma USA Inc.'s Wilate (von Willebrand Factor/Coagulation factor VIII Complex), saying it had made a mistake in granting the exclusivity. (See BioWorld Today, Aug. 10, 2012.)

Meanwhile, the FDA has not described the type and amount of evidence necessary to demonstrate clinical superiority for orphan exclusivity, choosing instead to follow a case-by-case approach laid out in a final rule adopted last year.

In response to industry comments seeking guidance on demonstrating superiority, the agency said when it released the rule that it was considering the feasibility of issuing draft guidance on "what may constitute a plausible hypothesis of clinical superiority for certain categories of products."