The World Conference on Lung Cancer (WCLC), which was held virtually on 28-31 January, provided an opportunity for Janssen and Takeda to showcase their latest data investigating the use of their respective epidermal growth factor receptor (EGFR) targeting agents, amivantamab and mobocertinib. Both drugs are designed to treat patients harbouring tumours with EGFR exon 20 insertions mutations. The two drugs have distinct mechanisms of action, as Janssen’s amivantamab is a bispecific antibody targeting activating and resistance EGFR mutations and MET aberrations, while Takeda’s mobocertinib is a tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertions specifically. There are currently no approved targeted therapies available for this mutation, indicating an unmet clinical need for this group of patients and representing an underserved aspect of the non-small cell lung cancer (NSCLC) market. Comparisons between the two agents indicate that Janssen currently has the edge over its competitor.
The recent news that Janssen has filed in the US and Europe suggests the drug will likely have first-mover advantage, and Takeda will likely follow swiftly if mobocertinib receives approval by the end of the year, as expected. Both received breakthrough designation status, which will expedite the process. A second advantage lies in the data. Although cross-trial comparisons should be treated with caution, amivantamab appears to have a marginal advantage, particularly when assessing key clinical endpoints and serious adverse events associated with treatment. In terms of progression-free survival (PFS), amivantamab had a median PFS of 8.3 months while mobocertinib had a median PFS of 7.3 months. The PFS benefit is similar, and a conclusion cannot be drawn due to the small patient population in each trial and the subsequent wide confidence intervals. Median overall survival (mOS) was 22.8 months with amivantamab, while the mOS data was not shown for mobocertinib. Furthermore, overall response rates were higher with amivantamab.
The most pertinent differentiating factor between the two drugs is their safety profiles. Key opinion leaders interviewed by GlobalData indicate that the high prevalence of diarrhoea with mobocertinib treatment, which occurred in 90% of patients and as grade 3/4 events in 21% of patients, could dissuade physicians from using the drug. In contrast, severe adverse events with amivantamab were rarer or more manageable. A final advantage may lie in amivantamab’s mechanism of action, which acts by targeting two escape routes for therapeutic resistance: EGFR Exon 20 and MET. Mobocertinib only targets EGFR Exon 20. Currently available data are unable to establish the benefit of this combined approach, but the rationale for its benefit is clear, given the known link between MET amplification and EGFR-TKI based resistance. One advantage for mobocertinib is the route of administration, specifically that it is orally administered compared to amivantamab’s intravenous administration. This advantage may be particularly beneficial during the Covid-19 pandemic when convenient at-home administration is preferred.
The Exon 20 Insertion market will be established in 2021, and Janssen currently looks to have the advantage over Takeda. Takeda can minimise this advantage by providing clear instructions on how to manage or reduce severe adverse events associated with mobocertinib treatment.