Drug development is rapidly outpacing our ability to bring companion diagnostics to market. These other orphan drugs are approved with a CDx in the label, but no FDA approved (or CE marked) diagnostic yet available. I started thinking about this following the approval of dabrafenib and trametinib for a pan-tumor / solid tumor V600E mutation. At this time, there is no CDx approved for pan tumor use. There are, however, plenty of BRAF-testing options available, including CDx options for NSCLC and melanoma, and physicians should have no challenges finding BRAF testing options for their patients:
This prompted me to look back for other examples of orphan CDx assays. Some examples below. I’m tracking these manually, based solely on recollection and requests from my colleagues for input, and I have likely missed a few. I have also not included instances where there was a delay of only a few months.
- Novartis’ dabrafenib and trametinib. No pan-tumor BRAF V600E assay
- Immunocore’s Kimmtrak®. No FDA-approved test for HLA typing yet available (but many LDT and IVD options out there)
- Blueprint’s Ayvakit®. No FDA-approved test for PDGFRA Exon 18 yet available
- Merck KGaA’ Tepmetko® for MET. No FDA-approved test for MET exon 14 (but one is available for capmatinib)
- Merck’s Keytruda®. FDA-appoved/CE-marked MSI test only recently approved
- Bayer’s Vitrakvi®. FDA-approved NTRK fusion test lagged drug launch by about a year
- Lilly’s Retevmo®. FDA-approved RET fusion/mutation test lagged drug launch by more than a year
I believe this is the tip of the iceberg. With so many novel immuno-oncology drugs moving into pivotal studies in phase 2, and so many of these targeting novel biomarkers that are not currently available in the current ecosystem (eg, EGFR, PDL1, etc.) I predict many more drugs approved long before a commercial, kitted companion is available. This need not be a hindrance, however.
In our experience, the FDA has permitted the use of local, lab-developed tests (LDTs) to fill the gap until a CDx is ready. NeoGenomics has supported numerous drug launches using an LDT as part of a sponsored test program, most recently for Lilly and Bayer’s products described above.
- NeoGenomics and Bayer Collaborate to Offer NTRK Testing for Certain Colorectal and Thyroid Cancer Patients
- NeoGenomics Inc. Announces Partnership with Lilly for Lung Cancer Sponsored Testing Program Utilizing the NeoTYPE(R) DNA and RNA Assay
Finally, the rise in super-specialized, novel, rapidly developed drugs that require a CDx option means that we may see more use of single-site tests as opposed to distributable kits. This will be a topic for a future blog.