Is a Challenge to FDA’s “Route-of-Abuse” 3-Year Exclusivity Approach to Abuse-Deterrent Drug Products on the Horizon?April 6, 2017
The intersection of exclusivity and off-label promotion issues is not common, but quite an interesting issue nevertheless. A recent press release from Egalet Corporation (“Egalet”) raises the possibility that FDA may be challenged – perhaps in court – as a result of the Agency’s decision to, on the one hand, broadly interpret the scope of 3-year new clinical investigation exclusivity in the context of abuse-deterrence drug products to apply to a particular route of abuse and not to a particular abuse-deterrent formulation; and, on the other hand, to allow a company to promote off-label its abuse-deterrent drug product for a particular route of abuse protected by another manufacturer’s 3-year exclusivity.
FDA approved Egalet US, Inc.’s NDA 208603 on January 9, 2017 for ARYMO ER (morphine sulfate) Extended-release Tablets for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. With that approval, FDA issued a statement, titled “Impact of Exclusivity on Approval of Arymo ER.” FDA’s statement explains that although intranasal route of abuse clinical studies were conducted with ARYMO ER (as well as intranasal route of abuse clinical studies), the Agency determined that 3-year exclusivity granted to Inspirion Delivery Technologies, LLC’s (“Inspirion”) MORPHABOND (morphine sulfate) Extended-release Tablets (NDA 206544) prevented the Agency from approving ARYMO ER with labeling describing abuse-deterrence via the intranasal route of abuse. The period of 3-year exclusivity applicable to MORPHABOND, which expired on October 2, 2018, is coded in the Orange Book as “M-189,” which is definfed as “LABELING DESCRIBING THE EXPECTED REDUCTION OF ABUSE OF SINGLE-ENTITY EXTENDED-RELEASE MORPHINE BY THE INTRANASAL ROUTE OF ADMINISTRATION DUE TO PHYSICOCHEMICAL PROPERTIES.”
As we previously reported (here and here), although FDA first publicly articulated with the approval of ARYMO ER a route-to-abuse approach to 3-year exclusivity for abuse-deterrent drug products, the Agency had been developing that position over the past few years. In coming to this decision, FDA rejected a narrower approach to the scope of 3-year exclusivity, such as limiting ot to a specific abuse-deterrent formulation, or to a specific abuse-deterrent technology.
Dissatisfied with FDA’s exclusivity determination, Egalet met with FDA officials in February 2017 and raised two issues with the Agency, according to an Egalet press release:
- Whether FDA would reconsider its exclusivity determination for MorphaBond with respect to intranasal abuse-deterrent properties; and
- Whether FDA would likely take enforcement action against Egalet if Egalet disseminated materials to healthcare practitioners regarding ARYMO ER’s intranasal abuse-deterrent properties and the studies demonstrating the effects of these properties.
FDA responded to Egalet in writing on March 27, 2017 “indicat[ing] that the first issue remains under consideration.” As to the second issue raised by Egalet, “the FDA letter specifically stated that the Agency ‘does not object’ to Egalet’s stated plans for distribution of materials that are ‘based on the intranasal abuse-deterrence data in its original NDA submission’ if the communications are directed only to healthcare professionals, include appropriate disclosures and are otherwise truthful and non-misleading,” said Egalet in a press release.
If FDA ultimately reaches a split decision – affirming the Agency’s route-of-abuse determination on the scope of 3-year exclusivity (as we suspect FDA will do), and sticking to its non-objection policy on off-label promotion – then we may be in a position where no affected party is happy . . . Egalet or Inspirion. And history tells us that that type of situation can be a recipe for controversy.