A small but growing number of pharmaceutical companies are using the US Food and Drug Administration’s Voluntary Genomic Submission program “strategically” to help populate phase III trials with genetically favorable volunteers, according to a senior FDA official.
Felix Frueh, associate director of genomics at the FDA, told Pharmacogenomics Reporter recently that sponsors have begun using the 2-year-old VGDS program to ensure that members of the agency’s clinical review division who may not fully understand genomics can see what the company’s pharmacogenomic goals are for a candidate drug before deciding on the sponsor’s request for populating a phase III study.
“What started out as a voluntary program has become a tool that industry is using during the drug-development program to strategically position the genomic information in their programs that interact with” the portion of the agency overseeing that drug, said Frueh.
Frueh used as an example a drug maker ready to submit data from a phase IIa study to the FDA’s clinical division. “In order to prepare for phase III studies, the sponsor used a scheme by which they analyzed the phase II studies with genetic and genomic tools in order to stratify according to what they perceived to be a better efficacy signal.”
Had the sponsor instead gone straight to the clinical division with the genetic data, “the reception at the FDA would have been a little bit more problematic simply because the clinical division doesn’t necessarily have the expertise and technical understanding of how that stratification protocol came about using the genomic information,” said Frueh.
Frueh said out of the 10 or so VDGS submissions the FDA has received in 2006, between three and five have been used in this way. He added that the FDA is seeing this happen “more frequently.”
Asked whether this gambit has paid off for pharmas, Frueh said, “Yes.” He said he knows of two cases in particular that successfully populated a phase III trial using genetic data filtered through the VGDS program.
“Submitting the genomic finding under the VGDS program and discussing the technical approach and the way forward from a genomics perspective … in [an end-of-phase II] meeting that included the clinical review division helped … set the stage [for the company’s phase III goals] so that the clinical division already understood” the genomic component involved.
Stressing that the process is completely legal, Frueh said in this case the clinical review committee would say, “OK, we know what that is, we know what it will be used for, so now let’s talk about how to use it for phase III.”
He said sponsors’ use of the VGDS program in this way “was not a specific intention of the FDA” when it launched it in 2004, “but it became clear that this is definitely one of [its] big benefits and drivers.”
He said in creating programs like VGDS “you have effects [that] you perhaps don’t necessarily anticipate, but because you create these opportunities, they emerge. And there is a benefit for both sides — the sponsors and the FDA — for having these types of interaction possibilities.”
“What started out as a voluntary program has become a tool that industry is using during the drug-development program to strategically position the genomic information in their programs that interact with” the portion of the agency overseeing that drug.
Frueh agreed that the VGDS program has enabled many sponsors to begin viewing the agency not as an adversary but as a partner. “The FDA is viewed as approachable,” he said. “It’s no longer viewed as an institution that, if you can avoid them you do. It’s actually a resource that can help sponsors better strategically position or identify options in their development programs to move a program forward.”
Frueh also said that 2006 was the year that the VGDS program saw “a turning point” in that the FDA “started to see a significant change in the type of data that was submitted.”
Early on, he said, the agency received “fairly limited” amounts of data with “fairly limited complexity.” In fact, the agency received “a lot” of VGDS data from drugs that Frueh described as “dead.” But in 2006, he said, “we really started to see highly complex data sets, many [using] Affymetrix GeneChip gene-expression arrays or whole-genome scans.”
Frueh said this “really helped us to understand what the industry is using genomics for in drug development programs.”