Chi-Med touts fruquintinib's phase 3 safety edge in relapsed colorectal cancer

Chi-Med's fruquintinib poses less severe liver toxicity than current therapies in colorectal cancer.

In a late-stage study presented at the American Society of Clinical Oncology meeting, Hutchison China MediTech’s VEGF inhibitor fruquintinib showed it could help relapsed patients with advanced colorectal cancer live longer, delivering a median overall survival of 9.3 months compared with 6.57 months for patients on placebo.

Tested in patients with locally advanced or metastatic colorectal cancer (mCRC) who'd failed on two previous rounds of therapy, fruquintinib also posted an advantage in progression-free survival. The drug held off the cancer's advance for a median 3.71 months, compared with 1.84 months in placebo patients.

The data add to the Hong Kong company's case for fruquintinib as it prepares to file for an approval in China. The company is also developing the med in other indications.

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The trial was carried out in China on 416 patients, most of whom had only been treated previously with chemo drugs rather than targeted therapies like Roche’s Avastin, which are more commonly seen in Western countries. That chemo-heavy approach might have contributed to the high OS rate posted by fruquintinib, Chi-Med CEO Christian Hogg noted in an interview with FierceBiotech.

What’s perhaps more encouraging about fruquintinib is its safety profile, Hogg said. Except for such side effects as hypertension, and the dermatological and gastrointestinal reactions commonly associated with VEGF drugs, the rate of liver toxicity patients in that arm of the study experienced was generally lower, Hogg said.

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Around 70% of mCRC patients have liver metastases or compromised liver function, and fruquintinib’s metabolism depends on a functioning liver, Hogg explained. If routine monitoring turns up hepatotoxicity, patients have to stop therapy until their numbers return to normal—and that obviously interferes with the success of treatment. “The tumor would be back growing aggressively immediately if treatment is interrupted,” said Hogg.

Bayer’s Stivarga, a multikinase inhibitor already approved in the U.S. as a third-line treatment for mCRC, carries an FDA black box warning on hepatotoxicity. In its pivotal Correct trial, dose interruptions affected more than 60% of patients because of adverse events. In its own trial, 35% of fruquintinib patients saw their doses interrupted.

In the Correct trial, Stivarga posted a median overall survival of 6.4 months, compared with placebo’s 5 months. Without a head-to-head study, however, differences in efficacy and safety between the two drugs can't be definitively drawn.

But fruquintinib's safety and efficacy data suggest the drug "can be an important new treatment option for patients whose colorectal cancer continues to progress,” said Jin Li, primary investigator of the Fresco trial and director of the department of oncology at Tongji University-affiliated Shanghai East Hospital.

Chi-Med is wrapping up its fruquintinib application with China’s FDA, and if the drug is approved, partner Eli Lilly will be responsible for marketing. The two companies aren't likely to pursue an approval in the U.S. for the same indication, Hogg said, though he wouldn't rule it out.

That's primarily a cost-effectiveness consideration: Stivarga has already become an established third-line treatment, and even with an additional approval in gastric cancer, the med turned in only €275 million ($310 million) in 2016.

RELATED: Bayer's struggling Stivarga moves closer to liver-cancer lifeline with FDA 'priority' tag

Chi-Med figures there's more opportunity for the med in its home country. Chi-Med picked third-line mCRC as a “lower-risk indication with big unmet need in China,” said Hogg, as there’s no medication approved in the field there.

The company estimates new CRC incidence in China to be at around 50,000 to 60,000 annually. With that, the company expects peak sales for fruquintinib for that indication to reach $110 million to $160 million, based on a 20%-25% penetration.

Additionally, a pivotal study in China is examining fruquintinib as a third-line non-small cell lung cancer treatment, with readout expected in the second half of next year.

In January, Chi-Med started a phase 2 study that combines fruquintinib with AstraZeneca’s Iressa for first-line treatment of advanced or metastatic NSCLC in China. The company is also exploring the med’s possibility in combination with Taxol in gastric cancer in a phase 3 soon to be initiated.

In the future, Chi-Med will continue to “leverage the clean safety profile of fruquintinib” and “look for combinations in innovative areas,” including with immunotherapies, Hogg said. To him, the med’s ability to combine is “a multibillion-dollar opportunity.”

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