GSK bolts-on immuno-oncology candidate with €3.7bn Merck deal

GlaxoSmithKline is making another big play in cancer, signing a wide-ranging deal with Merck KGaA for M7824, an immuno-oncology drug that made a splash at last year’s ESMO meeting.

The global alliance gets off the ground with a 300 million euro payment to Merck from GSK to secure co-development and co-marketing rights to the bifunctional fusion protein immunotherapy, an anti-PD-L1/TGF beta trap in clinical trials for solid tumours including non-small cell lung cancer (NSCLC).

The deal includes another €500 million tied to a lung cancer programme and €2.9 billion in additional development and commercial milestones that takes the totally tally to a hefty €3.7 billion (around $4.2bn).

The excitement at ESMO stemmed from phase I data showing a much higher response rate with M7824 (bintrafusp alfa) in patients with NSCLC than would be expected with first-generation PD-1/PD-L1 inhibitors such as Merck & Co/MSD’s Keytruda (pembrolizumab), which dominates the NSCLC market.

The result lent credence to the German drugmaker’s hypothesis that M7824’s dual antagonism of PD-L1 and TGF beta provides a double-whammy that could mean more patients respond to the cancer immunotherapy. At the moment, around a third of patients treated with the first generation of PD-1 inhibitors as a monotherapy don’t respond.

If M7824 can outperform Keytruda in this setting it could unlock a multibillion-dollar market in NSCLC alone, leaving aside its potential in other tumour types. Merck and GSK are planning an ambitious development programme, with at least eight trials of the drug on the go by the end of this year.

The data with M7824 has caught GSK’s eye as it continues a revamp of its pipeline and operations launched by CEO Emma Walmsley when she took over the helm of the company in 2017, with a big push into oncology spearheaded by new R&D chief Hal Barron.

“M7824 brings together two different biological functions in a single molecule and we have observed encouraging clinical results in treating certain cancer patients,” said Barron of the new alliance. “Despite recent medical advances, many patients with difficult-to-treat cancers don’t currently benefit from immuno-oncology therapies leaving them with limited treatment options.”

Cancer isn’t the only area of focus for the new GSK, but it is certainly an important one, and the Merck deal coming shortly after the company paid $5.1 billion to acquire Tesaro and its PARP inhibitor Zejula (niraparib) for ovarian cancer, a rival to AstraZeneca’s class-leading Lynparza (olaparib).

The Tesaro deal also brought in a PD-L1 inhibitor and other assets that Walmsley said had doubled GSK’s immuno-oncology pipeline, even before the Merck alliance.

GSK pretty much exited the cancer market commercially when it sold its marketed products to Novartis in 2015, but with big deals now done for the company’s consumer health and vaccines divisions—and a planned separation of consumer health from pharma—the company has refocused its attention on its pipeline.

That includes candidates like its in-house developed BCMA-directed antibody-drug conjugate GSK2857916 for multiple myeloma, which according to EvaluatePharma could be a blockbuster by 2024 – assuming it launches on schedule next year. That programme has already picked up a breakthrough designation from the FDA, and a speedy review may be needed as the anti-BCMA pipeline is getting fairly crowded.

Another key project is GSK3377794, a NY-ESO-1-targeted T cell therapy that GSK licensed from Adaptimmune and is in several clinical trials in cancers including sarcoma, myeloma, NSCLC, melanoma and ovarian cancer.

For Merck, it might have been expected that M7824 would have attracted the attention of Pfizer, already its partner for underperforming checkpoint inhibitor Bavencio (avelumab), and it is possible that GSK had to outbid its rival or other suitors to claim control of the asset.

According to Merck’s CEO Belén Garijo, “GSK clearly emerged as the ideal partner due to their strong commitment to oncology, and the complementary talent and capabilities they will bring to our alliance.”

The two companies will jointly conduct development and commercialisation of M7824, with all profits and costs from the collaboration being shared equally on a global basis.