FDA clears Novartis’ Tabrecta for METex14 lung cancer

Novartis has secured accelerated approval in the US for Tabrecta, the first targeted therapy for advanced non-small cell lung cancer (NSCLC) with a specific genetic biomarker known as MET exon 14 skipping.

Tabrecta (capmatinib) inhibits MET tyrosine kinase, an enzyme associated with cancer cell growth and metastasis, and has been approved alongside Foundation Medicine’s FoundationOne CDx assay, a companion diagnostic that  detects the METex14 biomarker.

The oral, twice-daily drug has been approved by the FDA ahead of a rival MET inhibitor from German drugmaker Merck KGaA – Tepmetko (tepotinib) – which was approved in Japan in March but has not yet been cleared by the FDA.

It’s also reached the market ahead of Pfiz­er’s MET/ALK inhibitor Xalko­ri (crizotinib), which has been available for years for NSCLC caused by other mutations but was grant­ed break­through ther­a­py sta­tus for METex14-positive patients in 2018.

It has been proffered as one of seven drugs Novartis aims to bring to market this year with the potential to make $1bn-plus in sales – assuming it can encourage the use of the diagnostic test.

Lung cancer is the most common type of cancer worldwide, with 2 million cases diagnosed annually, with NSCLC accounting for around 85% of all cases. METex14 mutations are seen in around 3-5% of call cases of NSCLC, and tend to occur in tumours that are particularly aggressive.

There are around 4,000-5,000 cases of METex14-positive NSCLC each year in the US, and Tabrecta can now be used to treat these patients, regardless of whether they are previously-untreated or have been given other drugs in the past. It’s expected to launch sometime this week with a list price of $17,950 for a 28-day supply before rebates or discounts.

The FDA granted accelerated approval to Tabrecta based on a clinical trial which showed that patients treated with the drug had an overall response rate of 68% in previously-untreated patients – with a complete response seen in 4% – and 41% with no complete responses among those who had received prior drug treatment.

At last month’s virtual AACR congress, Novartis also reported data showing that Tabrecta treatment also led to a response in seven of 13 METex14 NSCLC patients whose cancer had spread to the brain.

Tabrecta’s approval triggers a $70m milestone payment to Incyte, which originally developed the drug and will also receive 12-14% royalties on net sales. Incyte is also in line for up to $500m in milestone payments from Novartis under the terms of their 2009 licensing agreement for the drug.