ESMO: Eyeing another shot at US market, Hutchmed touts 'practice-changing' colorectal cancer data

Back in 2018, Hutchmed’s fruquintinib became China’s first homemade drug approved locally in a major cancer type. Now, armed with a global trial win, the Chinese biotech is targeting the U.S. colorectal cancer market, with eyes on Bayer and Taiho Pharma.

Fruquintinib cut the risk of death by 34% over placebo in heavily pretreated patients with refractory metastatic colorectal cancer, according to data to be presented at the 2022 European Society for Medical Oncology congress. Both groups of patients also received best supportive care.

If eventually approved, fruquintinib, known as Elunate in China, could go up against Bayer’s Stivarga and Taiho Pharma’s Lonsurf in third-line colorectal cancer. For fruquintinib, “we’re talking about practice-changing study results,” Hutchmed’s international chief medical officer Marek Kania, M.D., said in an interview.

Kania argued Lonsurf and Stivarga have somewhat “suboptimal” clinical data. After all, the two meds were approved in colorectal cancer about seven to 10 years ago. Riding an evident need for new treatment options, fruquintinib’s current FRESCO-2 trial finished enrolling nearly 700 patients across the globe in about 15 months starting mid-2020 despite the pandemic, Kania noted.

In FRESCO-2, fruquintinib extended the median time patients had lived by 2.6 months to 7.4 months. The drug also pared down the risk of tumor progression or death by 68%, as those who took the Hutchmed VEGFR inhibitor went 3.7 months without disease worsening, compared with 1.8 months for the control group.

By comparison, Lonsurf showed a death risk reduction of 31% in the RECOURSE trial by extending the median life expectance of third-line patients by two months to 7.2 months. As for Stivarga, the pivotal CORRECT trial showed the Bayer therapy reduced the risk of death by 23%, and it prolonged patients’ lives by just 1.4 months to 6.4 months at median.

But the colorectal cancer treatment landscape has changed a lot since those study readouts. Fruquintinib seemed to have achieved better results in a more advanced patient population. Besides traditional chemotherapy, Avastin and EGFR inhibitors that were available in Stivarga’s and Lonsurf’s trials, patients in fruquintinib’s FRESCO-2 had also tried Stivarga and Lonsurf, an anti-PD-1 inhibitor if they had microsatellite instability-high tumors and a BRAF inhibitor if eligible.

In fact, only about 20% of patients today fit Stivarga’s and Lonsurf’s clinical profile, Kania said, citing real-world data.

The 34% death risk reduction was better than the 27% Hutchmed had anticipated while designing the study, Kania said. And the 4.8-month median life extension was almost the same as the company’s expectation of five months.

“These results are exciting and encouraging for patients and healthcare providers alike since they address a huge unmet need in refractory metastatic colorectal cancer,” Arvind Dasari, M.D., from the University of Texas MD Anderson Cancer Center and an investigator in FRESCO-2, said in a statement. “Fruquintinib provides a possible new treatment option with a meaningful survival benefit and manageable toxicity profile.”

While the patient population in FRESCO-2 had failed multiple lines of treatment, Hutchmed is still gunning for a third-line colorectal cancer indication with its regulatory filing to the FDA, Kania said. That’s because FRESCO-2 showed consistent results as in the original FRESCO trial in third-line Chinese patients.

The original FRESCO trial was similar to Stivarga’s and Lonsurf’s patient population in that patients hadn’t previously received newer options other than chemo, Avastin and EGFR inhibitors. There, Elunate cut the risk of death by 45%, as patients on the Hutchmed drug lived a median 9.3 months, compared with 6.6 months for placebo.

Fruquintinib marks Hutchmed’s second try at the U.S. market. The FDA in May rejected the company’s application for surufatinib in neuroendocrine tumors because of China-only phase 3 data.

Hutchmed isn’t concerned about fruquintinib hitting a similar roadblock, Kania said. FRESCO-2 was designed in close consultation with regulators at the FDA, the EMA and Japan’s Pharmaceuticals and Medical Devices Agency, and it’s a global trial conducted in 14 countries, including the U.S.

Now, Hutchmed is gearing up for a pre-application meeting with the FDA in October, Kania noted. Partnered with Eli Lilly in China, Elunate registered 26% sales growth in the first half of 2022 to $50.4 million.

Colorectal cancer is the third most common cancer worldwide. In the U.S., an estimated 151,000 people will be diagnosed with colorectal cancer this year, according to data from the National Cancer Institute. By Hutchmed’s estimate, about 55% of patients move on to third-line therapy from second line, and about 20,000 colorectal patients in the U.S. are on third-line therapy.

With the two positive FRESCO trials, Hutchmed is running several proof-of-concept studies testing various combinations of fruquintinib as well as in earlier lines of treatment, Kania said. These include a pilot study in the adjuvant setting for post-surgery use in certain early-stage patients at high risk of recurrence.