‘Clinical Superiority’: FDA Finds Diazepam Nasal Spray Deserves Orphan Exclusivity

Regulatory NewsRegulatory News | 13 January 2020 |  By 

Thanks to the last user fee agreement, known as the FDA Reauthorization Act of 2017, the agency can now explain why a newly approved orphan drug is clinically superior to previously approved orphan drugs and therefore should be awarded seven years of orphan drug exclusivity.

Since 2017, FDA has only explained how five treatments can be considered clinically superior, with the latest coming last Friday for Neurelis Pharmaceuticals’ Valtoco (diazepam nasal spray). FDA explains how diazepam was previously approved as a gel administered rectally whereas Valtoco’s intranasal route of administration is easier to use.

“In the context of when this drug is to be given, typically in the middle of a seizure event, it is inherently easier to administer the drug to a patient intranasally than rectally,” FDA said.

The four other drugs to obtain such clinical superiority findings and win the orphan exclusivity from FDA since 2017 include:
  • Pfizer’s Mylotarg (gemtuzumab ozogamicin) in September 2017, after it was initially withdrawn from the market following an accelerated approval in 2000, but was approved later for a lower dose and different schedule that was found to have less early mortality, less hepatotoxicity, less veno-occlusive disease, more rapid platelet recovery and less hemorrhage, FDA said.
  • CSL Behring’s Hizentra (Immune Globulin Subcutaneous (Human), 20% Liquid) in March 2018 because the previously approved intravenous formulation requires a central venous access device, which is associated with an increased risk of thromboembolic events and access-associated infections.
  • Astellas Pharma’s Prograf (tacrolimus granules for oral suspension) in May 2018 because “tacrolimus granules for oral suspension provides an age appropriate formulation for pediatric patients that avoids the severe risks associated with erroneously compounded tacrolimus,” FDA said.
  • Novartis’ Signifor LAR (pasireotide) in June 2018 for the treatment of Cushing’s disease because FDA said the dosing regimen of the long-acting release (once monthly) provides a major contribution to patient care over the dosing regimen of the previous, immediate release (twice-daily) version.
Moving forward, drug developers looking to obtain this “clinically superior” tag for their orphan products should look to 21 CFR 316.3(b)(3), which defines how a drug can provide a significant therapeutic advantage over an already approved drug (that is otherwise the same drug) in one or more of the following three ways:

“(i) Greater effectiveness than an approved drug (as assessed by effect on a clinically meaningful endpoint in adequate and well controlled clinical trials). Generally, this would represent the same kind of evidence needed to support a comparative effectiveness claim for two different drugs; in most cases, direct comparative clinical trials would be necessary; or

(ii) Greater safety in a substantial portion of the target populations, for example, by the elimination of an ingredient or contaminant that is associated with relatively frequent adverse effects. In some cases, direct comparative clinical trials will be necessary; or

(iii) In unusual cases, where neither greater safety nor greater effectiveness has been shown, a demonstration that the drug otherwise makes a major contribution to patient care.”

For more on the determinations, FDA publishes summaries of the clinical superiority findings when a drug is eligible for orphan-drug exclusivity. The FDA Law Blog also offers more information on some of the superiority determinations before 2017.


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy