The US Food and Drug Administration (FDA) on Tuesday finalized guidance on developing antiviral drugs for recurrent herpes labialis (RHL), commonly referred to as cold sores, which affects between 20% and 40% of adults in the US.
Specifically, the guidance details FDA's expectations for drugmakers to develop and test antiviral drugs to treat or prevent RHL from preclinical pharmacology and toxicology considerations to recommendations for designing Phase II and III clinical trials.
While FDA has approved some antiviral drugs to treat RHL, such as Denavir (penciclovir) and Famvir (famciclovir), the agency has not approved any drugs to prevent the disease.
According to FDA, the final guidance is largely the same as the draft version issued in July 2016, with minor editorial changes and the omission of a requirement for a toxicity adverse event grading scale.
In the draft version, FDA said that sponsors should "provide a toxicity grading scheme for clinical trials … with the understanding that toxicities with a relatively low grade assignment may be less acceptable in healthy populations commonly enrolled in RHL clinical trials compared to populations in clinical trials of drugs for diseases such as cancer or human immunodeficiency virus."
In the guidance, FDA says that sponsors of investigational drugs for RHL will need to undergo standard Phase I safety studies, followed by proof-of-concept and dose-ranging Phase II studies, which FDA says can be of similar design to Phase III studies.
FDA also says that the number of Phase II studies necessary to progress to Phase III will depend on the treatment and the results of at least one Phase II study, and that the primary objective of those studies will be to show a reduction in duration of an RHL episode by at least half a day.
For new previously-approved drugs studied in a new formulation or route of administration, FDA says that sponsors should discuss their early clinical development plans with the agency, as such drugs may not need extensive Phase I studies, though in cases where an oral drug is being developed for topical use, FDA says additional dermatologic safety testing may be needed.
For Phase II and III studies, FDA says sponsors should aim to enroll adults and adolescents that have at least four episodes of RHL per year.
FDA says that sponsors developing investigational drugs for RHL will typically need to conduct two Phase III superiority trials, though in some cases "a single persuasive and clinically meaningful study for each indication (treatment and prevention) submitted together may provide substantial evidence of effectiveness sufficient for approval of both indications."
For sponsors looking to test a drug already approved to treat RHL for a prevention indication, FDA says that a single superiority study may be sufficient. Though for drugs being developed only for a prevention indication, FDA says that data from two Phase III trials is strongly recommended.
FDA, Federal Register Notice