Can A Cancer Drug Originated In China Be A Success In The U.S.?
While China has prospered in a variety of technologies over the last decade, one area where growth has been slow has been in innovative drug R&D. This is not surprising. Going from an idea to a marketed product can take 15 years and easily cost more than a billion dollars. Moreover, China has long focused on traditional medicines, slowing its entry into pharmaceuticals.
This is now about to change. As described by Rebecca Robbins in STAT, the Chinese drug maker, Chi-Med, is nearing approval in China for an innovative drug that was discovered and developed by its own scientists. The drug, known as fruquintinib, is a VEGFR inhibitor (types 1, 2, and 3) which can prevent tumor access to blood vessels thereby preventing them from getting nutrients needed to survive. Such antiangiogenesis drugs are often used in combination with other cancer therapies and are approved in the West to treat a variety of cancers. Chi-Med is seeking approval from the Chinese regulatory authorities for the use of fruquintinib to treat patients with colon cancer who have already failed at least two other chemotherapies.
Currently, there is only one other such orally active VEGFR inhibitor approved in China for the treatment of colon cancer - Bayer’s Stivarga (regorafenib). But, as Robbins points out, this is expensive and difficult to obtain outside of China’s leading medical centers. Furthermore, fruquintinib is a very selective VEGFR inhibitor whereas Stivarga hits not only VEGFR but also another enzyme, TIE2. Chi-Med believes that fruquintinib’s better selectivity will render it safer and more effective, but this has yet to be proven.
Given the homegrown status of fruquintinib, as well as its potential therapeutic profile, it is likely that once approved fruquintinib will supercede Stivarga in China. As colon cancer is the fourth most common cancer in China, this drug can prove to be a commercial success as well. Chi-Med is so bullish on its drug, that it plans to bring fruquintinib to the U.S. market. As Robbins has pointed out, Chi-Med has opened up an office in New Jersey to facilitate U.S. development and it is in the process of finishing a U.S. phase 1 study
But, is this a wise decision? The phase 3 development program that Chi-Med ran in China compared fruquintinib to placebo. Of the 416 patients with metastatic colon cancer who had failed two lines of chemotherapy, those treated with fruquintinib had statistically significant longer median survival (9.3 months) compared to those on placebo (6.6 months). These results were published in the Journal of the American Medical Association perhaps to stimulate interest for fruquintinib in the U.S.
However, all of the clinical data that Chi-Med has generated thus far has been comparing fruquintinib to placebo. To be frank, running a placebo-controlled study in the U.S. would be difficult in that, for ethical reasons, a positive control would need to be used as the comparator and not placebo. Furthermore, to have any chance at both FDA approval and acceptance from payers, Chi-Med will need to prove that fruquintinib is at least as effective as other therapies, like regorafenib. Chi-Med faces other challenges as well. While fruquintinib and regorafenib are oral pills, antibody VEGF inhibitors like Roche’s Avastin are widely used in the U.S. to treat colon cancer. Even if Chi-Med could get FDA approval for fruquintinib, that approval is going to take at least 5- 7 years to achieve – more than a decade after the current VEGF inhibitors have been available to patients and oncologists. Fruquintinib would have to be extraordinarily superior to the established therapies in order to gain a foothold in the market. Finally, there is pricing to consider. Generic or biosimilar competition for the VEGF inhibitors currently used in the U.S to treat colon cancer will be emerging as fruquintinib reaches the U.S. shores. As a result, its commercial prospects will be further dimmed.
There are tremendous issues that Chi-Med faces in its U.S. gambit. Fruquintinib may not be the best test case for bringing a homegrown China medicine to the U.S.