Sidley Austin LLP filed a petition (here) requesting that FDA not grant orphan drug exclusivity to a ready-to-use version oral solution of vigabatrin. There are currently two versions of vigabatrin already approved with a number of generics available. The original approved NDA products (tablet and power for reconstitution) were granted orphan drug exclusivity (ODE), the last of which expired in 2016.

The Sidley petition argues that the new dosage form of ready-to-use oral solution should not qualify for ODE award and states the following:

“The 1983 Orphan Drug Act (ODA) amended the FDCA by adding Sections 525-528 to the Act. Section 527 establishes the conditions under which FDA must recognize orphan-drug exclusivity. Added to the statute in 2017, subsection (c) of Section 527 states that when the same drug (with “drug” understood to mean “active moiety”) has been previously approved as a treatment for the same rare disease, the sponsor of the subsequent drug can obtain exclusivity only by demonstrating that its product will be clinically superior to all existing versions of that active moiety. The term “clinically superior” is defined to mean “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.”

Sidley’s argument is preemptive in nature, and they make some interesting arguments in their petition. But, in my opinion, the issue really boils down to one important point. How thin can the bologna be sliced in deciding whether the new product provides a major contribution to patient care? The ready-to-use oral solution sponsor obtained orphan drug designation (ODD) in 2022 and Sidley argues in part, that a change in dosage form is not sufficient in this case to warrant a new period of ODE for that yet-unapproved product. They make various arguments that there does not appear to be any clinical superiority as there is no evidence that the sponsor has performed any clinical studies. They argue that adding a flavoring agent to taste mask the product also does not qualify them for ODE. They further claim that adding preservatives may pose a safety issue to infants and they indicate that the product would be no safer regarding potential medication errors than the already approved powder for reconstitution.

The issue, however (as I see it), revolves around the improved convenience of having a ready-to-use product rather than a product where the powder must be reconstituted prior to use. There have been a number of challenging decisions the FDA has had to make relative to the impact of patient convenience or a major contribution to patient care, where a second period of ODE has been awarded to an active ingredient for the same indication where a subsequent product was approved during another sponsor’s existing ODE period or where the ODE award was for the same drug for the same indication after another sponsor’s ODE had expired. These decisions by FDA have been rare and centered mostly on dosing regimen changes (for example where a daily injection was required), and a subsequent applicant developed a product where the injection was only needed once a month, clearly a significant benefit to the patient. Another example centered on a drug that had to be administered every six (6) hours around the clock, requiring patients, including pediatric patients, to be awakened in the middle of the night for dosing, while the new product only had to be taken once every 12 hours.

So, while Sidley’s arguments and request is somewhat speculative in nature, they also mention that they have no objection to the ready-to-use product’s ODD and would not object to granting ODE if for some reason there is something beyond their current knowledge of the pending NDA. However, they object to the Agency granting ODE if the sole basis is on the new dosage form and the convenience issue.

We must all remember that the grant of ODD does not guarantee the award of ODE as that decision is not made until the proposed product gains FDA approval. But the preemptive strike will be an interesting one to watch as it may further define how the bologna is sliced when the issue of providing a major contribution to patient care is the key in the decisional process at FDA.