In less than 24 hours, the FDA handed out one rejection and one thumbs-up to two rival drugs for a rare stomach cancer.
On the heels of turning down Blueprint Medicines’ Ayvakit as a therapy for heavily pretreated patients with gastrointestinal stromal tumors (GIST), the FDA has green lit Deciphera Phamaceuticals’ Qinlock (ripretinib) as the first drug specifically approved in that same setting.
Deciphera’s pricing Qinlock at $32,000 per month, the same as Ayvakit’s wholesale acquisition cost, and it’s launching the drug this week. Noting that Qinlock is the only next-generation drug allowed to treat KIT-driven GIST, SVB Leerink analyst Andrew Berens projected it could generate $1.6 billion in all lines of therapy in the U.S. and key EU countries.
Qinlock’s approval came three months ahead of schedule, as the FDA evaluated it under its real-time oncology review pathway, which allows for data submission as they come in rather than waiting for the entire package. The application has also been put under Project Orbis, a collaboration with drug regulators in Australia and Canada. Those two countries’ agencies are still examining the application.
The new kinase inhibitor proved its worth in the phase 3 Invictus study, showing it could cut the risk of disease progression or death by 85% in advanced GIST patients who had received such prior therapies as Novartis’ Gleevec, Pfizer’s Sutent and Bayer’s Stivarga. The median progression-free survival was 6.3 months for Qinlock and 1.0 months for placebo. Qinlock also helped cut the risk of death by 64%, as patients who received it lived a median 15.1 months, compared with 6.6 months in the placebo arm.
Previously, Blueprint’s Ayvakit had failed to top Stivarga at staving off GIST tumor progression or death in the Voyager trial. Its median progression-free survival of 4.2 months did even worse than Stivarga’s 5.6 months, leading to an FDA rejection last week.
In a Monday note to clients, Berens noted that Qinlock’s label on the safety side is less favorable than expected. Specifically, it warns about heart dysfunction and requires monitoring, which the SVB Leerink analyst argues “may be relevant in older patients with pre-existing heart failure.”
After Ayvakit’s Voyager trial flop, Blueprint has abandoned its plan to pursue any additional GIST indications other than its current indication for a small subset of patients whose tumors carry a PDGFRα exon 18 mutation. But for Qinlock to realize its blockbuster peak sales estimate, it still has some proving to do in the second-line Intrigue study, whose enrollment is expected to be completed by year's end with a data readout in 2021.
Berens currently assigns $1.36 billion in U.S. and EU combined peak sales for Qinlock in second-line GIST. Outside of those territories, Zai Lab has licensed Greater China rights to Qinlock through a 2019 deal worth up to $205 million.
CStone holds Ayvakit’s China rights and already has its new drug applications in both fourth-line and PDGFRα exon 18-mutant GIST accepted by the National Medical Products Administrations.