After 18 years in development, AstraZeneca’s CTLA-4 antibody gets the red carpet treatment at the FDA
After a decade, a second CTLA-4 antibody may finally be on its way to approval.
AstraZeneca announced Monday that the FDA had given priority review to tremelimumab, its long-gestating CTLA-4 antibody, in combination with the PD-L1 inhibitor Imfinzi for patients with liver cancer that can’t be treated with surgery.
The Big Pharma’s application is based on a multi-year, 1,324-patient study that showed 30.7% of patients who received a “priming dose” of tremelimumab followed by Imfinzi were alive after three years, compared to 20.2% of patients who received Bayer’s sorafenib, the standard of care.
Susan Galbraith, AstraZeneca’s cancer R&D chief, called that data “unprecedented.” Others raised questions about how the data held up compared to an alternative treatment regimen being developed by Roche, and how much benefit the CTLA-4 antibody offered, given that patients who received Imfinzi alone showed nearly identical survival at the two-year mark. The difference only emerged after three years.
Nevertheless, the three-year data were notable given how other PD-1 inhibitors have done in the same setting when tested on their own. Opdivo failed to show an advantage over standard of care in one trial, and Merck has struggled to show that Keytruda offers a meaningful advantage either.
Tremelimumab has had plenty of its own stumbles. Pfizer first put the drug in trials in 2004, but abandoned it soon after, following disappointing early results. It was still years before Bristol Myers Squibb showed blocking CTLA-4 could dramatically extend the lives of a subset of melanoma patients, jumpstarting the immuno-oncology field and making tens of billions of dollars for Merck and Bristol Myers.
AstraZeneca licensed Pfizer’s drug in 2011, hoping to get in on the still nascent immuno-oncology field, but it failed continually in trials, including in lung, urothelial, and head and neck cancer.
Although the drug would only be OK’d for a limited indication, an approval would make it the second CTLA-4 antibody on the market and the first contender to Bristol Myers’ Yervoy since it was approved in 2011.
AstraZeneca is also hoping to get an approval soon in combination with Imfinzi in metastatic lung cancer, although it is unclear how much benefit the new drug offers over Imfinzi alone.