The relative ease of marketing a laboratory-developed test (LDT) in the US means it is hard to see why a company would choose to go through the much stricter premarket approval process – especially as nothing more has been heard from the agency about its intention to bring LDTs under its control since last year’s Asco meeting.
But Myriad Genetics, among others, is doing just that with its breast cancer gene test BRACAnalysis. It has just started the PMA process for the test as a companion diagnostic to AstraZeneca’s olaparib, hoping to shore up sales now it faces growing competition in the LDT space (Myriad’s BRCA monopoly crumbles after Supreme Court denies gene patents, June 14, 2013). But, owing to differences in the labelling of drugs and diagnostics, this might not increase sales as much as test makers hope.
Speaking at yesterday’s AngloNordic Medtech conference in London, Merck Serono’s Birgit Reitmaier said companion diagnostics’ labels were much more specific than those of the drugs with which they are supposedly paired.
For example, the label of Qiagen’s therascreen KRAS RGQ PCR Kit states that it is to be used for “the identification of [colorectal cancer] patients for treatment with Erbitux (cetuxirnab) based on a K-Ras no mutation detected test result”.
Erbitux’s label states that it can be used to treat patients with “K-Ras mutation-negative (wild-type), EGFR-expressing, metastatic colorectal cancer as determined by FDA-approved tests”. In other words, Qiagen’s test can only be used with Erbitux, but Erbitux may be used with any approved test.
And there are two. The EGFR pharmDx test developed by Dako is also approved specifically for use with Bristol Myers-Squibb’s drug. For Herceptin, the situation is even worse: the FDA has sanctioned 10 different tests as companion diagnostics for Roche’s HER2 inhibitor.
But even this is not the real problem: despite the advice in the labelling, doctors do not have to use the approved test – they can instead use an LDT, or "homebrew" test.
More arduous route
Foundation Medicine, the sequencing company whose IPO succeeded so impressively last year, is also pushing into companion diagnostics. The company is working on a test to identify potential responders to Clovis Oncology’s rucaparib.
Developing companion diagnostics is tricky even if a developer faces no rivals. Most obviously approval of drug and test must be timed carefully if they are to coincide, as neither can be sold without the other. But Dr Reitmaier also pointed out that regulations vary widely across the world; even if the path is relatively clear in the US the situation will be trickier in Europe and in Asian countries.
Perhaps these companies have been spurred towards formal FDA approval because they believe that the agency will make good on its promise to take over the regulation of LDTs. If it does, tests already awarded a PMA will see their competition swept away (Vantage Point – FDA regulation of lab-developed tests could hurt smaller companies, June 19, 2013).
But this is something of a gamble. If the FDA wishes to make it worth a company’s while to negotiate the more arduous route to market and thereby ensure higher standards of efficacy, it ought to move forward with its plans to take over the regulation of LDTs.