FDA approve quick review of Bayer and Loxo’s biomarker targeting cancer drug
Loxo Oncology and Bayer have stated that they should be hearing from the FDA about their tumour biomarker-targeted cancer drug larotrectinib by 26 November, after picking up a priority review by the US regulator.
The TRK inhibitor Larotrectinib is being reviewed by the US regulator for adult and paediatric patients with locally advanced or metastatic solid tumours with a neurotrophic tyrosine receptor kinase (NTRK) gene fusion biomarker, a departure from the usual regulatory route of seeking approval based on the organ or tissue where the cancer starts to grow.
The trial data presented at last year’s American Society of Clinical Oncology (ASCO) meeting and since published in the New England Journal of Medicine (NEJM), displayed that larotrectinib achieved a 75% overall response rate (ORR) in TRK fusion cancers, including 13% complete responses and 62% partial responses.
The data sparked interest in the five-year-old biotech as analysts predicted that the drug could become $1bn product, although that is providing the Loxo and Bayer can work out how to commercialise the drug effectively and identify the patients who can benefit from it.
Loxo and Bayer are aiming to repeat something achieved by Merck & Co when it secured approval in the US for PD1 inhibitor Keytruda for all cancers, regardless of location in the body, which carry the microsatellite instability-high (MSI-H) biomarker. Noted to be the first time the FDA had approved a cancer drug based on a molecular indication.
Bayer bought into the programme last December, agreeing to pay $400m upfront for rights to larotrectinib and a follow-up drug (LOXO-195) that is being developed to tackle tumours that develop resistance to larotrectinib or other drugs within the TRK inhibitor class.
NTRK fusions are seen in a broad range of tumour types, including various forms of colorectal, lung, thyroid, breast and brain cancer, and have been linked to tumour development for more than 30 years. Only latterly have TRK inhibitors such as larotrectinib entered clinical testing, aided by tumour genome sequencing that can be used to identify patients who may benefit from treatment with these precision medicines. Loxo has previously estimated there could be up to 5,000 new cases of NTRK-positive tumours each year in the US alone.
A big challenge in the development of this type of biomarker-targeted drugs is the low incidence in each single tumour type, that offsets the broad distribution of mutations across cancer as a whole.
To try to address that issue, Loxo formed a partnership earlier this year with Illumina to develop a companion diagnostic, called TruSight Tumour 170, that will use sequencing to identify whether patients’ tumours carry a broad range of genomic signatures.
It will also test patients for another mutation (RET fusions) that are being targeted by Loxo’s RET inhibitor LOXO-292 and will be showcased at the 2018 ASCO conference when it gets underway next month.