A Milestone Moment For Pharmacogenomics: US FDA Ready To Drop ‘Voluntary’ Program
Executive Summary
The US FDA’s plan to update a 20-year-old guidance on pharmacogenomic data submissions is a good time to reflect on the dramatic transformation of industry attitudes and approaches to targeted medicine over the past two decades.
The US Food & Drug Administration’s new draft guidance on “Pharmacogenomic Data Submissions” is in one sense clearly overdue.
It is intended to replace a final guidance of the same name that was originally issued in draft form in 2003 and then finalized in 2005. Obviously, a lot has changed in two decades, and what was a brave new world component of drug development when the original guidance was released is now a well developed field with substantial experience.
From a regulatory perspective, it is time to treat the field like any other standard industry practice – like blood pressure monitoring or food effect studies – with the agency mapping out expectations for what types of information must be submitted, when and how.
But the new draft also provides an opportunity to reflect on how dramatically things have changed in drug development since that first version was issued. In just 20 years a new approach that was largely deemed a threat to blockbuster markets has now been embraced as an opportunity to optimize therapies – and, if anything, a field where the industry would love to be able to do much more to reinvent drug development.
It may be hard to remember now, but at the start of the new millennium most Big Pharma companies viewed pharmacogenomics as a very risky proposition, seeing it as a tool that could be used to restrict indications by weeding out potential non-responders or people who might be at heightened risk of adverse events.
The original guidance, in fact, was issued along with an effort by FDA to try to convince companies to share exploratory PKG studies by promising not to use the data for regulatory purposes. (Also see "Getting Personal: FDA's Plan to Save the Drug Industry" - Pink Sheet, 1 Sep, 2006.)
FDA issued the 2003 draft alongside a new initiative, the Voluntary Genomic Data Submission program. The VGDS was intended to encourage companies to share early exploratory research with the promise of agency feedback and support for potential further development – and a promise not to use it “against” the product in question for regulatory purposes. The idea was to allow sponsors to at least explore opportunities to identify subpopulations where their therapies may have optimal profiles without the threat FDA would unilaterally rewrite the indication before the sponsor could weigh the commercial implications fully.
The program was never vastly popular in industry, but it did serve its purpose. Indeed, a decade after the VGDS was launched, Deputy Commissioner Janet Woodcock (then the head of the Center for Drug Evaluation & Research) remarked on how dramatically attitudes had changed during workshop focusing on industry-driven initiatives to encourage the use of pharmacogenomics in drug development. (Also see "From “Safe Harbor” To Spotlight: Pharmacogenomics Comes Of Age At FDA" - Pink Sheet, 15 Oct, 2014.)
And now, a decade after that, FDA has decided it is time to end the VGDS itself. In a Federal Register notice announcing the new draft guidance, FDA also announces the likely end of the voluntary program. The new draft guidance removes references to the VGDS, and FDA notes that it has “established additional pathways to interact with stakeholders on biomarker development,” including the Biomarker Qualification Program and Critical Path Innovation Meetings, that can serve its original goals.
“Given the availability of these programs and decreasing use of the program, FDA is considering ending” the VGDS, FDA says. The notice offers a brief obituary of sorts: “The VGDS program created a pathway for voluntary exchanges between FDA and the pharmaceutical industry or other stakeholders regarding genomic and other biomarker studies in the context of individual drug development programs.
The program helped the Agency gain knowledge regarding genomics research in the context of drug development and practical experience with data submission and analysis,” FDA explains.
It was not, however, widely used, especially in recent years. FDA says that the program “has received over 50 voluntary submissions” since its introduction in 2003.
The Federal Register notice concludes with a request for further input from industry. “While it is FDA’s plan to discontinue the VGDS program in its current form, FDA requests feedback on the utility of maintaining a voluntary submission pathway that is of value to both FDA and the pharmaceutical industry,” the notice adds.