The FDA has started a priority review of Roche’s entrectinib for NTRK fusion cancers, setting up a market clash with Bayer.
Roche has submitted entrectinib for approval as a second-line treatment NTRK fusion-positive, locally advanced or metastatic solid tumours, or as initial therapy when there are no first-line options, as well as for the treatment of people with metastatic, ROS1-positive non-small cell lung cancer (NSCLC).
The FDA has granted Roche a breakthrough designation for entrectinib which means it should conduct a faster-than-usual review of the application, with an action date of 18 August.
Entrectinib is a tropomyosin receptor kinase (TRK) inhibitor that shuts down a range of tumour-associated pathways, including ROS1, NTRK and ALK, and has been tipped by analysts as a potential blockbuster product.
Bayer’s Vitrakvi (larotrectinib) was the first drug to reach the market for NTRK fusion cancers and also only the second to be approved by the FDA for a ‘tissue agnostic’ indication, focusing on the molecular profile of a tumour rather than its location in the body.
It was approved by the FDA as a first-line therapy for NTRK-positive cancers, a group which represents around 1% of all solid tumours and affects some 2,500 to 3,000 patients in the US each year.
If approved with the proposed indication, entrectinib would be an option for second-line therapy after Vitrakvi failure – although Roche has designs on moving the drug into first-line use with a phase 2 trial on the go. It will compete in first-line ROS1-positive NSCLC against Pfizer’s Xalkori (crizotinib), which is the standard-of-care in this setting and according to some analysts it is this indication which will drive the initial uptake of the drug.
Entrectinib’s initial application in NTRK fusions sets it up in opposition to Bayer’s Vitrakvi follow-up LOXO-195, renamed BAY 2731954 after the German drugmaker took control of the two drugs in the wake of Eli Lilly’s $8bn acquisition of originator Loxo Oncology last week.
Roche acquired rights to entrectinib when it bought Ignyta for $1.7bn just over a year ago, having licensed rights to the drug in a $1.55bn deal a few weeks earlier. It has previously said entrectinib could have an advantage over Vitrakvi because it penetrates into the central nervous system more effectively and so should be more effective at treating tumours that have spread to the brain.
Roche’s Sushil Patel
Roche’s head of global products strategy, Sushil Patel, said last year that the company expects entrectinib “to rapidly establish itself in the standard of care and set an important unmet need in ROS1, particularly in…CNS patients.”