It may not be on the same scale as the $5.1bn purchase of Tesaro, but today Glaxosmithkline made another huge bet on oncology, licensing Merck KGaA’s PD-L1 follow-on project M7824 for €300m ($343m) up front and a total possible spend of €3.7bn.
Merck has been talking M7824 up for several years now, stating repeatedly that the asset could put its own Bavencio in the shade. Bavencio is partnered with Pfizer, and Merck’s choice of Glaxo as partner for the newer drug is somewhat surprising; either the UK firm offered something Pfizer could not, or Pfizer was for some reason not interested.
M7824, now also going by the name bintrafusp alfa, is a bispecific fusion protein targeting TGF-β and PD-L1. Eight phase II trials are ongoing or are set to start this year, the most interesting is that pitting it directly against Keytruda in patients with PD-L1-expressing non-small cell lung cancer in a bid for first-line approval.
The terms of the deal illustrate just how much a slice of the first-line NSCLC pie might be worth. Milestone payments linked to lung cancer data, approval and sales are worth a total of €3.4bn, and though this cash is contingent on Merck hitting various targets it is still a huge pledge by Glaxo.
Investors also saw it as a big endorsement of M7824’s promise – Merck shares jumped 3% in afternoon trading following the deal’s announcement. The two companies will jointly share costs and profits worldwide; should the project move into pivotal trials, the German company could come to appreciate having a partner to split the bill.
Better than Keytruda?
Supporting Glaxo’s decision are earlier data, with a response rate in a phase I trial of 41% in immunotherapy-naive NSCLC patients expressing PD-L1 at greater than 1%, and 71% in high expressers (Asco 2018 – German Merck’s run at US Merck, June 4, 2018).
As an indirect comparison, Keytruda’s second-line trials scored an objective response rate (ORR) of around 30% in high expressers and around 19% in those with 1% expression or more. And Opdivo saw a 20% ORR in squamous disease and 19% in non-squamous.
Pfizer’s decision not to expand the existing Bavencio-based oncology alliance to include M7824 is as curious as Glaxo’s decision to sign. Bavencio was the fourth PD-(L)1 agent to be launched, and is overshadowed by Keytruda and Opdivo. Based on that experience, it could simply be that Pfizer did not believe it worth the gamble of trying to take on mighty Keytruda – and certainly not the €300m Glaxo was willing to spend.
Moreover, Pfizer’s interest in innovative oncology seems mostly in the realm of small-molecule agents, and to the extent that it has any interest in biologicals it is largely in biosimilars, like its version of Avastin.
In the checkpoint inhibition game, beating Keytruda seems to be the only sure route to blockbuster sales (Esmo 2018 – Without overwhelming efficacy the me-too PD-1 chase is futile, October 23, 2018). Merck has not taken the cautious route when it comes to developing M7824, and it must have needed a partner that was just as eager for a big score.
Glaxo wants to be an oncology player, and on the available evidence M7824 is one of the most promising assets out there. Now the asset's performance must justify the hype.
|Selected Merck KGaA-sponsored trials of M7824|
|Status||N||Setting||Data expected||Trial ID|
|Phase II||300||First-line NSCLC, vs Keytruda||Oct 2021||NCT03631706|
|Phase II||708||Solid tumors||Jun 2019||NCT02517398|
|Phase I/II||20||Triple-negative breast cancer||Oct 2019||NCT03579472|
|Phase I||114||Solid tumors||Dec 2019||NCT02699515|
|Phase I||59||Colon and rectal cancer||Nov 2019||NCT03436563|
|Phase I||20||Breast cancer||Dec 2019||NCT03620201|
|Phase I||20||Breast cancer||Sep 2019||NCT03524170|
|Source: EvaluatePharma, clinicaltrials.gov.|