FDA clears Loxo Oncology, Bayer's Vitrakvi for tumours driven by NTRK gene fusion, regardless of location

The FDA announced Monday that it granted accelerated approval to Loxo Oncology and Bayer's Vitrakvi (larotrectinib) to treat adult and paediatric patients with tumours harboaring an NTRK gene fusion. Specifically, the oral TRK inhibitor is indicated for solid tumours that have NTRK gene fusion without a known acquired resistance mutation, are metastatic or likely to result in severe morbidity if surgically resected, and have no satisfactory alternative options or have progressed following treatment.

FDA Commissioner Scott Gottlieb remarked "today's approval marks another step in an important shift toward treating cancers based on their tumour genetics rather than their site of origin in the body." Last year, Merck & Co.'s Keytruda (pembrolizumab) was approved by the agency for the treatment of any metastatic microsatellite instability-high or mismatch repair deficient solid tumour, marking the first time the regulator cleared a cancer drug based on the presence of a specific biomarker as opposed to its location in the body.

Gottlieb noted that the approval of Vitrakvi "reflects advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine." Gottlieb added "this type of drug development programme, which enrolled patients with different tumours but a common gene mutation, wouldn’t have been possible a decade ago because we knew a lot less about such cancer mutations."

Approval of Vitrakvi was supported by data from three clinical studies that included 55 paediatric and adult patients with solid tumours that had an identified NTRK gene fusion without a resistance mutation and were metastatic or where surgical resection was likely to result in severe morbidity. Results showed that the drug was associated with a 75 percent overall response rate across different types of solid tumours, with 73 percent of responses lasting at least six months, and 39 percent lasting a year or more at the time results were analysed.

Vitrakvi will be priced at $32 800 per month for the oral capsule version, while an oral liquid formulation for some children and adults will cost $11 000 a month. Bayer spokewoman Sasha Damouni said "for the majority of patients, we expect that monthly out-of-pocket costs will be $20 or less." Bayer also indicated that a refund will be offered if patients don't see a clinical benefit after three months of treatment with Vitrakvi. With regard to clinical benefit, Damouni suggested that the patient's doctor would determine the goal that needs to be met, be it total or partial tumour clearance or even a halt of disease progression.

According to Bayer, between 2500 and 3000 patients in the US develop cancer due to a TRK fusion each year, with analysts at Oppenheimer forecasting that annual sales will reach more than $1 billion by 2024. For related analysis, see ESMO 2018 analysis: Loxo, Bayer showcase larotrectinib credentials as US approval decision nears.

Bayer entered into a partnership with Loxo last year in a deal worth potentially more than $1.5 billion to jointly develop Vitrakvi, as well as other cancer drugs. A marketing application for Vitrakvi was submitted to the European Medicines Agency in August.

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