NEW YORK – Starting Thursday, Merck KGaA's Tepmetko (tepotinib) is available in England to advanced non-small cell lung cancer patients with MET exon 14 skipping mutations, following a final recommendation from the National Institute for Health and Care Excellence.
Patients with MET exon 14 gene skipping alterations make up about 3 to 4 percent of NSCLC cases, but they have a disproportionately poorer prognosis than patients without these tumor markers.
The European Commission recently approved Tepmetko for patients with previously treated NSCLC harboring METex14 gene skipping alterations. Like NICE, the EC considered data from Merck's Phase II VISION trial, in which 46 percent of patients responded to Tepmetko and the median duration of response was 11.1 months.
Tepmetko also received accelerated approval in the US for the same indication last year. And it was approved in Japan in 2020, along with a companion diagnostic from ArcherDx that detects METex14 gene skipping mutations in tissue and plasma.
In spite of that track record, NICE's recommendation was more than a rubber stamp on other regulators' decisions. Merck's original submission to NICE's appraisal committee grouped together previously treated and untreated subgroups. The committee deemed that inappropriate because it combined groups who would be eligible for different comparator treatments based on histology, PD-L1 tumor proportion scores, and whether they had been previously treated or not.
The committee was particularly concerned that the data from the single-arm VISION trial might not be generalizable to the population served by the National Health Service. NICE further disagreed with Merck's use of a real-world comparator cohort, noting that the cohort did not include any people from the UK and the comparator treatments are not used in this setting in the UK.
The committee ultimately accepted a new indirect treatment comparison from the company, using data from VISION and trials involving wild-type NSCLC patients, while still noting a high degree of uncertainty. NICE agreed to finally recommend Tepmetko based on this new data, finding that the drug extended life by more than three months in the previously treated subgroup and that the treatment was a cost-effective use of NHS resources.
The list price for Tepmetko is £7,200 ($9,395.32) for 60 x 250 mg tablets. NHS England, NHS Improvement, and Merck have inked an agreement to provide Tepmetko at an undisclosed discount.
Dame Sue Hill, CSO and senior responsible officer for genomics at the NHS, said in a statement that a genomic test that can identify patients with MET exon 14 skipping alterations will be added to the National Genomic Test Directory. "This means patients carrying the gene mutation can benefit from the most effective treatments, and it's a great example of how the NHS Genomic Medicine Service is harnessing the power of genomics to deliver precision medicine straight to patients," Hill said.
NICE estimated that more than 700 people in England are eligible to receive Tepmetko as either a first- or second-line treatment.