Growing competition in the RET/MET space in non-small cell lung cancer following the fourth approval in 2020

GlobalData Healthcare 2 October 2020 (Last Updated October 2nd, 2020 16:07)

Growing competition in the RET/MET space in non-small cell lung cancer following the fourth approval in 2020

On 7 September, Roche announced that the FDA had approved Gavreto (pralsetinib) for the treatment of adults with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. This indication was approved under the FDA’s Accelerated Approval Program, based on data from the Phase I/II ARROW study. Gavreto, a second-to-market RET inhibitor, will challenge Eli Lilly’s first-to-market Retevmo (selpercatinib), approved in May this year. Gavreto is jointly commercialized by Genentech, a wholly owned member of the Roche Group, and Blueprint Medicines in the US. RET fusions represent a small subset of non-squamous NSCLC patients, accounting for approximately 1%–2% of patients, therefore representing a narrow indication for the two pharma giants.

Targeting specific oncogenic drivers in niche biomarker restricted populations for NSCLC has been a running theme of 2020, with approvals of two MET inhibitors, Novartis’ Tabrecta (capmatinib) and Merck’s Tepmetko (tepotinib) (the latter in Japan) earlier this year. As with RET fusions, MET aberrations occur in a small fraction of non-squamous NSCLC patients, accounting for approximately 3%–4% of patients. The commonality of advanced NSCLC creates a viable commercial opportunity for pharmaceutical companies developing agents targeting niche molecular aberrations.

In terms of differentiating the competitors, the RET inhibitors Gavreto and Retevmo are considered to be very similar agents. A first-to-market advantage will likely be minimal given the rarity of the actionable mutation, meaning that physicians will not have become accustomed to using Retevmo in less than a year. Retevmo has the marginally better efficacy data; however, there is a danger comparing the two drugs across different trials due to the different baseline characteristics of the patient groups in the respective trials. One differentiating factor is the safety profile, with QTC prolongation more common with Retevmo and anemia more common with Gavreto.

The comparison between the MET inhibitors, Tabrecta and Tepmetko, is more interesting. Tabrecta is currently FDA-approved while Tepmetko is expected to be approved in the US at the end of the year or early next year. The optimal diagnostic test for identifying a MET Exon 14 skipping event is RNA-based. Merck’s Tepmetko companion diagnostic, the Archer DX panel, is both DNA- and RNA-based, while Novartis’ Tabrecta companion diagnostic, the FoundationOne CDx, is DNA-based, clearly outlining an advantage for Tepmetko. This initial difference may ultimately lead to the drug being the favored agent amongst physicians unless Novartis ensures an improvement to its companion diagnostic, crucially introducing an RNA-based element. Greater competition in these spaces leads to competitive pricing, a wider array of treatment options, and ultimately better patient outcomes. The NSCLC R&D space once again highlights the success of translating the identification of an oncogenic driver into an actionable biomarker in the clinic, and the disease area continues to serve as the poster child for modern personalized medicine.