MWC welcomes landmark results for lung cancer drug
A novel lung cancer drug with strong development links to the MWC has shown impressive results in a large-scale international trial. Currently under review by the European Medicines Agency and under priority review with the US Food and Drug Administration, the drug’s success highlights the impact of our scientists on the global stage.
MWC researchers based at the Auckland Cancer Society Research Centre (ACSRC) have long specialised in the development of drugs targeting a particular class of molecules within cancer cells called “tyrosine kinases”. One of the most important such molecules in cancer biology is called the epidermal growth factor receptor (EGFR), and this is the target of the new drug, dacomitinib, which blocks its action irreversibly.
In 2017, the development of this drug reached a major milestone when it was proven to be effective against a form of lung cancer in a late stage clinical trial (a large multinational phase III study called ARCHER 1050, in non-small-cell lung cancer). MWC Investigator Associate Professor Jeff Smaill, based at the ACSRC, welcomed the news.
Jeff led the New Zealand side of a research collaboration with Pfizer in Ann Arbor that discovered dacomitinib. The project began with an earlier drug Jeff had made, called canertinib. This drug did not make it through to clinical use, but the subsequent collaboration with Pfizer sought to improve it by tweaking its chemical structure. The project resulted in the discovery of dacomitinib, and its selection for clinical development in 2003.
The story of this medicinal chemistry success was finally published in the Journal of Medicinal Chemistry in 2016. Later that year the team also published a book chapter describing the “scale up” of the chemistry – the development of processes that enabled them to produce 400 kg of the drug, so that it could enter the clinic.
“Chemists in New Zealand and the US spent about a year making well over a hundred compounds and testing them. Detailed evaluation eventually led to dacomitinib being the winner,” says Jeff. “Even though it was selected for clinical trials back in 2003, it's taken this long to come through the process, and finally show success in this large phase III trial.”
“It's very gratifying for the team of chemists in Auckland that did the hard work to see the final drug do well in phase III and come out as a leading compound of its type,” Jeff adds. “This shows us again that New Zealand scientists are making a big contribution globally – but it also shows that to develop drugs you need to have teams like ours with the right expertise – and you have to be in it for the long haul.”
Jeff and his long-term biology collaborator Associate Professor Adam Patterson lead an MWC Flagship programme developing novel third generation tyrosine kinase inhibitors that are activated only in the low oxygen environment of human tumours. Clinical trials of their first drug in this class, called tarloxotinib, began in 2012 and are anticipated to continue through 2019.
Thumbail image courtesy of © Sebastian Kaulitzki | Dreamstime.com