Getting Agency Centers to Work Together
Not all industry observers share that sentiment. “We view the new draft guidance as a clear indication of FDA’s interest in streamlining the approval process for companion diagnostics,” concluded Brian Marckx, an analyst with Zacks Equity Research, in a report.
Also weighing in on FDA’s draft guidance is the Personalized Medicine Coalition (PMC), an umbrella organization that represents more than 200 academic, industry, patient, provider, and payer communities. Amy M. Miller, Ph.D., PMC’s public policy director, told GEN that the draft guidance provides clarity on FDA’s current thinking on regulating companion diagnostics, long a source of concern to the drug and device industries.
In its draft guidance, FDA envisions collaboration between its drug and device centers but does not offer specifics. “There’s very little detail about how that’s going to actually work. If that works well, it will speed up clearance of these products. But if that does not work well, it could slow it down,” Dr. Miller pointed out.
In its 2009 report “The Case for Personalized Medicine,” PMC said more than 1,300 genetic tests exist that signal inherited susceptibility to a wide range of conditions: “While not every test has a therapeutic option, a genetic diagnosis often permits targeted prevention or mitigation strategies.” Dr. Miller said the report is being updated, with the new edition—including new data—set to be published in the fall.
Sometimes, even simultaneous approval of a drug and its companion diagnostic is no guarantee that problems won’t arise later. In 2009, FDA updated the labeling for two colorectal therapies already on the market, Vectibix (Amgen) and Erbitux (Eli Lilly and subsidiary ImClone), to inform doctors that patients with KRAS mutations would not respond to these drugs.
Vectibix and Erbitux are anti-epidermal growth factor receptor (EGFR) antibodies approved at the same time with their original companion diagnostic, developed by partnering with Danish firm DAKO. But evidence that KRAS mutation status would affect how subjects responded to anti-EGFR treatments became apparent only after the decisive clinical trials for these antibodies were conducted. Amgen and Imclone analyzed the existing retrospective information, finding that about 43% of patients—those with KRAS mutations—did not respond to the EGRF inhibitors.
Qiagen’s DxS subsidiary later signed agreements with both drug companies to develop a KRAS companion test for Vectibix and Erbitux and pursue approvals from FDA for those tests along with the drug developers. FDA to date has yet to approve Qiagen’s KRAS test. In the meantime, a number of laboratories are marketing tests that detect KRAS mutations but have not been cleared through the agency.
Concurrent Dx/Rx reviews have the potential to bring promising new drugs and their companion diagnostics to market faster. But for that to happen, drug and diagnostics companies will need to consult with FDA earlier in the development process.
Just as diagnostic firms will have to work closely with drug developers, so will the drug and device centers at the FDA. How much progress is made toward goals set by the agency will determine how effective the concurrent Dx/Rx review process telegraphed by FDA in its Draft Guidance will be in bringing life-saving therapeutics and diagnostics to the patients who need them.