Loxo Oncology has been seeking a partner to provide a companion diagnostic for larotrectinib, its tumour-agnostic TRK inhibitor, and has found one in Illumina. A version of Illumina’s next-gen sequencing-based TruSight Tumor 170 panel is to be developed as a companion for both larotrectinib and LOXO-292, a phase I RET inhibitor.
As well as the usual difficulty of co-ordinating the approval of a drug and its companion test, the companies have set themselves an additional task: getting the FDA’s blessing for the test as a Class III device to detect NTRK fusions and RET fusions/mutations, and separately as a less risky Class II product for general tumour profiling. While these separate approvals ought to have advantages when it comes to reimbursement, the validation efforts will have to be pretty stringent.
The TruSight Tumor 170 panel can detect a variety of mutation types – fusions, splice variants, indels (insertions or deletions), single nucleotide polymorphisms and amplifications – across 170 genes linked to solid tumours.
The new US approval efforts will be spearheaded by Illumina, as will a planned European CE marking. The Class III companion diagnostic approval, if and when it arrives, ought to permit the test to be performed not just at Illumina facilities but by any laboratory that has one of Illumina’s NextSeq 550Dx machines, on which the test is run. TruSight Tumor 170 costs $8,000, according to Leerink analysts.
And there’s more. Seeking Class II and III approvals should permit Illumina to piggyback off a Medicare coverage decision secured last month by the genomic testing group Foundation Medicine.
The Centers for Medicare and Medicaid issued a National Coverage Determination for next-generation sequencing as a diagnostic laboratory test for patients with certain stage III or IV cancers, in response to Foundation Medicine’s application for Medicare coverage of its FoundationOne CDx test.
FoundationOne CDx is not a tumour-agnostic companion test in the same way as TruSight Tumor 170 is intended to be, but arguably amounts to much the same thing. It is approved in the US as a companion to a multiplicity of targeted cancer drugs developed by a range of manufacturers for a range of tumours.
The upshot is that assays that are approved or cleared by the FDA are now covered by Medicare, and if TruSight Tumor 170 duly receives a Class III for NTRK and Class II for broad tumour profiling, the labs running it will be able to obtain reimbursement for its use in all stage III and stage IV cancer patients.
For Illumina the deal means a chance to expand sales of its instruments and tests for clinical, rather than research, applications. The clinical market is believed to make up around 45% of its revenues.
And for Loxo inclusion of LOXO-292 in the companion diagnostic development plans is a nice boost before the presentation of data from its phase I trial at Asco.
Blueprint Medicines is also set to present phase I results on BLU-667 in RET-fusion cancer at AACR, a potential headwind for Loxo, though the partnership with Illumina and early focus on developing a companion diagnostic could provide benefits down the road, particularly if Class II designation for the tumour profiling is granted. Blueprint is developing a companion test for BLU-667 with Thermo Fisher, based on the latter’s Oncomine Dx Target Test, but only in non-small cell lung cancer.
And lastly there is a third party for which the Loxo-Illumina deal is good news: Bayer, which licensed larotrectinib and the follow-up anti-TRK LOXO-195 for $400m up front last November. Bayer has stated that genetic testing will be vital for driving larotrectinib sales, and believes that routine use of genetic panels could uncover a greater prevalence of NTRK mutations than currently estimated (Interview – Bayer’s need for deals grows, March 1, 2018). Bayer will welcome anything that expands larotrectinib’s reach as much as the other two companies involved.