2005D-0183 Guidance for Industry on Antiviral Drug Development Conducting Virology Studies and Submitting the Data to the Agency
FDA Comment Number : EC4
Submitter : Mrs. Gretchen Trout Date & Time: 07/28/2005 06:07:13
Organization : Schering-Plough
Category : Drug Industry
Issue Areas/Comments
We appreciate the Agency's support for the development of antiviral agents targeting novel pathways, however we have the following comments. Developing novel agents, like the CCR5 receptor antagonists, is particularly challenging given the constraints and limitations of available HIV entry and phenotypic assays. The state of the assay development trails behind the advances being made in drug development of these compounds. The lack of a robust assay that is reliable and clinically meaningful is a potentially significant impediment to efficient clinical drug development. Moreover, testing for coreceptor phenotype will likely have repercussions for labeling and future clinical patient management. It would be helpful if the Agency would provide clearer guidance to Sponsors regarding the role of the assay in determining potential labeling, and clinical use of these new compounds. We recognize the importance of understanding the mechanism of action and efficacy and safety profile of these agents, however, given the limitations of the assay, the requirements for testing during clinical development may be considered burdensome and too dependent on an imperfect test. Specifically, there is little reason to believe that the mechanism of emergence of tropism shifts will be very different from drug to drug in this class. It would therefore be entirely appropriate for each Sponsor developing a CCR5 receptor blocker to look at a reasonable number of clones from a small number of patients with tropism shifts and for the agency to look at the combined data rather than requiring each Sponsor to study a large number of clones. We would also urge the Agency to take a leadership role in fostering greater dialogue between all stakeholders: the Agency, Academia, Sponsors, and those developing the assays. Finally, this class of drugs may be more appropriate for use in treatment-naive or early-stage patients rather than late-stage patients despite the greater medical need of the latter. The longer study periods mandated for studies in the treatment-naive population and the attendant costs, however, are little incentive for Sponsors to study early-stage disease ahead of treatment- experienced patients.