Merck KGaA — Tepmetko FDA Review (NDA214096, ORIG 1, 2021)

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The FDA's multi-discipline review of NDA 214096 recommends accelerated approval for Tepmetko (tepotinib) for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations. This recommendation is based on objective response rates and duration of response from the VISION study, demonstrating clinically meaningful results in both treatment-naïve and previously treated patients. Preclinical studies showed tepotinib's efficacy in inhibiting c-Met phosphorylation and anti-tumor activity in various xenograft models, with an acceptable safety profile in animals, though liver and embryo-fetal toxicities were noted. Clinical pharmacology supports a 500 mg once-daily dose with food, showing acceptable efficacy and safety, with no dose adjustment needed for mild/moderate renal or hepatic impairment. The VISION study's efficacy data, including a median duration of response of 11.1 months, supports the unmet medical need. Safety analysis revealed manageable adverse events, with common issues including edema, hypoalbuminemia, and increased creatinine. No REMS was required, but post-marketing studies are requested to confirm benefit and further evaluate drug-drug interactions.

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