CEO SUMMARY: Although GlaxoSmithKline PLC is several years away from having a deliverable product from its Antigen Specific Cancer Immunoassay (ASCI) Program, it has a development deal with Abbott Laboratories to produce a companion diagnostic test for ASCI-based products. The interesting twist in this arrangement is that the resulting companion diagnostic assay will be designed to run on Abbott’s m2000 molecular system. That would allow an expanded number of labs to run this test kit.
IN THE MARCH TOWARD PERSONALIZED MEDICINE AND COMPANION DIAGNOSTICS, a recent deal provides an early peek at how pharmaceutical companies and in vitro diagnostic (IVD) manufacturers are likely to collaborate to their mutual benefit.
Additionally, the reasons behind this deal provide insight about how the Food & Drug Administration (FDA) is considering the relevance of a companion diagnostic test as it reviews applications for new therapeutic drugs.
This summer, GlaxoSmithKline PLC (GSK) and Abbott Laboratories, Inc., issued a press release disclosing a development deal between the two companies. Abbott Molecular will develop a PCR-based molecular diagnostic test designed to run on Abbott’s m2000 molecular instrument platform. Both GSK and Abbott will commercialize the resulting PCR test.
This assay will be used to identify expression of the MAGE-A3 antigen in non-small cell lung cancer (NSCLC) tumors. The results of the test will be used to determine which patients are candidates to receive GSK’s MAGE-A3 Antigen Specific Cancer Immunotherapy (ASCI). This is a therapeutic vaccine and is currently in clinical trials. Only patients expressing MAGE-A3 on their tumor will be eligible for this therapy and could potentially respond to treatment with GSK’s MAGE-A3 ASCI vaccine.
For pathologists and clinical lab administrators, the reasons behind this collaboration to develop a companion diagnostic test are instructive. They show why pharma companies will be more actively involved in clinical diagnostics, as well as how the FDA’s thinking about companion diagnostics is evolving.
Discussions With The FDA
In fact, GSK and Abbott got together because of input from the FDA. In July, Pharmcogenomics Reporter stated that a GSK spokesperson had told it that “It was clear from regulatory discussions that in order to launch a therapy for MAGE-A3, a regulatory approved companion diagnostic would need to be available.”
Thus, once GSK understood that it would need a companion diagnostic test to screen and qualify patients for its MAGE-A3 Antigen Specific Cancer Immunotherapy, it went looking for a suitable partner to create an effective screening test. Abbott apparently fit the bill and will develop the assay.
Indications are that GSK and Abbott will seek market approval for both the therapeutic vaccine and the companion diagnostic at the same time. Notably, this may not happen for a number of years, maybe as long as five or more years from now.
That’s because GSK’s MAGE-A3 ASCI vaccine is still in clinical trials. Its latest long term Phase III study of lung cancer is not projected to complete enrollment of 2,270 patients until 2011. Thus, there is no firm timetable for when market approval applications would be filed with the FDA.
The declared intention of both collaborators that the companion diagnostic test will be developed to run on the Abbott m2000 automated analyzer is interesting. There are two reasons why this is true.
First, because the Abbott m2000 already has market clearance from the FDA, there are established steps required to demonstrate the new companion assay meets specifications and produces reliable results when run on the instrument system. In turn, it is more likely that FDA reviewers would accept the data about the test’s performance because it was designed to be performed on the FDA-cleared Abbott m2000 automated system.
Second, by selecting Abbott as its partner to develop the MAGE-A3 antigen assay, GSK can later benefit from existing Abbott customers now using the m2000 instrument system. It gives GSK a rapid way to build up the number of laboratories that can perform the companion diagnostic test in support of physicians treating the cancer patient.
Third—and a benefit that often goes undiscussed—by developing its compan- ion diagnostic test on an FDA-cleared automated instrument platform, GSK can have higher confidence that the lab test result produced by the laboratory is clinically accurate, reliable, and reproducible. In other words, there should be less variability in the sensitivity and specificity performance of the test across the different labs performing the assay.
This is important to GlaxoSmithKline. Unacceptable rates of false positives and false negatives produced because of analytical variability among labs performing the companion diagnostic test can have significant consequences to the successful introduction, acceptance, and sustained use of the MAGE-A3 ASCI vaccine.
Every false positive means that a lung cancer patient lacking the MAGE-A3 expression would then get the vaccine—but would unlikely enjoy any identifiable therapeutic benefits. False positive patients getting this vaccine would skew the outcomes data in a detrimental manner.
In the case of a false negative, not only would the patient miss rightly being prescribed the vaccine, but GSK would lose the prescription and the revenue that comes with it. The outcomes data would also be skewed because of the false negatives.
These examples explain why pharmaceutical companies will want to be “hands on” in the way the companion diagnostic test is developed and how it is performed by different laboratories once it and the therapeutic drug have regulatory clearance to be sold in the market.
Although the companion assay to be developed by GSK and Abbott is probably a half decade or more away from market approval and clinical use, the circumstances that created this development collaboration already give pathologists and lab managers an opportunity to see one aspect of how personalized medicine and companion diagnostics are likely to evolve.