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FDA Advisors Raise Red Flag on Data for Cancer Vaccine T-Vec
The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) and Oncologic Drugs Advisory Committee (ODAC) have questioned clinical trial data submitted by Amgen for its dual-acting cancer vaccine/viral therapy talimogene laherparepvec (T-Vec). Amgen is seeking approval for the treatment of injectable regionally or distantly metastatic melanoma.
Of particular concern to the committees were the 278 subjects who dropped out of the study, leading the panels to question whether investigator bias –– focused on creating positive final data –– had something to do with those decisions. “Subject or investigator bias regarding the relative benefit of talimogene laherparepvec and the control [treatment] may have influenced the determination that it was in the best interest of the subject to stop treatment or to be given other therapy for melanoma,” the committees noted.
Their comments came 2 days before a scheduled FDA meeting to discuss whether T-Vec should be approved for its proposed indication.
The panels’ briefing document also states that there is “uncertainty regarding the meaningfulness of the observed responses,” with a small size of baseline lesions and a move by investigators to add patients as durable responders after the initial 6-month period for assessing responses.
The committees also concluded that there was no clear evidence of a systemic response to the drug. “Although there is a scientific basis to support the possibility that systemic effects may occur, the evidence in Study 005/05 that talimogene laherparepvec had a systemic effect was limited and difficult to quantitate,” the briefing document states.
Moreover, the reviewers raised the possibility of investigator bias in compiling the final data, with some patients being excluded in a way that may have skewed the final outcomes, even though the treatment flopped in terms of overall survival. According to the panels, “the survival results are not robust, and the conduct of the study with regard to a relatively small number of subjects, potentially subject to investigator bias, could have had substantial impact on the results of the survival analysis.”
“Uncertainty regarding the clinical meaningfulness of the Study 005/05 primary endpoint results, in the absence of a clear effect on overall survival, raises concern regarding both the existence and the magnitude of an overall benefit of talimogene laherparepvec,” the panels concluded.
Amgen acquired T-Vec, a re-engineered virus designed to kill cancer cells while provoking an immune response, in a $1 billion buyout of BioVex.
The FDA is not obliged to follow its advisory committees’ recommendations, but it usually does so.
Sources: FierceBiotech; April 27, 2015; and FDA Briefing Document; April 27, 2015.