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Scope of Orphan Drug Exclusivity – How Broad is Broad?

It has recently been reported that drugmakers have argued against broad orphan exclusivity for Eagle Pharmaceuticals, Inc.’s Bendeka® product. This was in response to the FDA’s invitation to applicants of certain products containing bendamustine to share how broad of a scope they believe Eagle’s seven-year orphan drug exclusivity for Bendeka should be, and if it should apply to Treanda®.

Before we get to the root of the argument, let’s refamiliarize ourselves with some previous events.

The Loophole

As previously blogged here, in June the US District Court for the District of Columbia ruled that the FDA must grant Eagle 7 years of marketing exclusivity for Bendeka (bendamustine hydrochloride injection) for the treatment of chronic lymphocytic leukemia and non-Hodgkin’s lymphoma. This was the second loss for the FDA regarding orphan exclusivity for the “same drug” that is not clinically superior (CS) to the approved product. This decision was similar to the Depomed court case, as we have previously blogged here.

Key to the court’s decision was the existence of a ‘loophole’ whereby the FDA’s Orphan Drug Regulations (specifically the requirement for a demonstration of CS in order to obtain orphan drug exclusivity (ODE) for a “same drug”) were NOT supported by the Statute [The Orphan Drug Act of 1983]. In the case of Eagle’s Bendeka, the Court agreed with the conclusion of Depomed that nothing in the statute’s text would leave room for the FDA to apply its “clinical superiority” requirement after an orphan drug has been designated and approved.

The text of the statute as it stood at the time of the FDA’s decision, before it was amended in 2017, was as follows:

Except as provided in subsection (b) of this section, if the Secretary approves an application filed pursuant to section 355 of this title for a drug designated under section 360bb of this title for a rare disease or condition, the Secretary may not approve another application for such drug for such disease or condition for a person who is not the holder of such approved application or of such license until the expiration of seven years from the date of the approval of the approved application

No mention is made in terms of CS.

This is in contrast to the FDA’s interpretation of the Orphan Drug Act as stated in the Code of Federal Regulations (CFR) (21CFR §316.34(c)): “If a drug is otherwise the same drug as a previously approved drug for the same use or indication, the FDA will not recognize orphan-drug exclusive approval if the sponsor fails to demonstrate upon approval that the drug is clinically superior to the previously approved drug.” [Definitions of “clinically superior” and “same drug” are provided in 21CFR §316.3(b)(3) and 21CFR §316.3(b)(14), respectively.]

The Ruling

As opposed to the FDA’s interpretation of the statute, the court ruled that “the plain language of the Orphan Drug Act requires the FDA to recognize exclusivity” if a company obtains approval of a drug designated as an orphan drug, and that FDA’s regulatory requirement that a demonstration of clinical superiority is needed to obtain orphan drug exclusivity is not supported by the statute.

Closing the Loophole

As part of the FDA Reauthorization Act of 2017 (FDARA), the statute was amended to prevent the apparent ‘loophole’ that allowed the same drug to get orphan exclusivity more than once without being clinically superior to the existing product.

Under the amended section 527, if a sponsor seeks ODE for an orphan-designated drug that is otherwise the same as a previously-approved drug for the same use, in order to receive ODE, the sponsor must demonstrate clinical superiority to “any” approved “same drug.”

New subsection 527(c) defines “clinically superior” to mean that “the drug provides a significant therapeutic advantage over and above an already approved or licensed drug in terms of greater efficacy, greater safety, or by providing a major contribution to patient care.”

Therefore, the FDA orphan drug regulations and statute (Orphan Drug Act) are NOW consistent with each other.

How Broad is Broad?

With this background information, we can now get to the drugmakers argument and the key question “how broad is broad?”

Critical to understanding the broad orphan exclusivity for Eagle Pharmaceuticals’ Bendeka is the “any” approved “same drug” in the regulations. The court required the FDA to grant 7-years ODE to Bendeka even though CS was not demonstrated for Bendeka over the previously approved product (Treanda), and Bendeka was determined to be the “same drug” as Treanda. Although the loophole is now gone the ruling is still in place, as FDARA does not change previously made rulings. This is causing chaos in the industry.

Based on the FDARA changes, any new application for a bendamustine product for the same indication prior to the expiry of ODE period will have to not only demonstrate clinical superiority to Bendeka but also to Treanda, as both of these products are considered “same drug”.

Eagle was well aware of this technicality as evident in their June press release:

As a result of the Court’s decision, the FDA will not be able to approve any drug applications referencing Bendeka until the ODE expires in December 2022. Moreover, the Company now does not expect generic Treanda entrants into the market until 2022, rather than November 2019”.

Apparently, other potential applicants did not find this broad scope appealing, and made arguments to the FDA against such broad exclusivity.

Fixing one conundrum sometimes leads to the creation of another. It will be interesting to see how this conflict plays out.

At Premier Consulting, we follow regulatory developments that affect orphan products closely so we can provide the best advice for our clients. To learn more about orphan drug opportunities and to obtain assistance in understanding the regulatory intricacies that may affect your program, contact us.


Stacey Ayres, PhD
Senior Director, Scientific and Regulatory Affairs