Following a recent high-profile rejection of Eli Lilly and Innovent Biologics’ immunotherapy, the FDA has turned down another cancer med developed in China and submitted with China-only pivotal trial data.
Monday, Hutchmed said the FDA has rejected its application for surufatinib in pancreatic and extra-pancreatic neuroendocrine tumors (NETs) with a complete response letter.
The drug is approved in China under the brand name Sulanda. But the FDA figured two phase 3 trials conducted in China and a small phase 1 bridging study in the U.S. weren’t enough for an approval in the U.S.
Now, the agency is asking Hutchmed to run a multiregional clinical trial with participants “more representative of the U.S. patient population and aligned to current U.S. medical practice,” the company said.
Pandemic-related issues regarding site inspections also “contributed to the FDA action,” the company added. Back in March, Hutchmed had said the FDA hadn’t inspected its manufacturing and clinical sites in China.
Hutchmed is now working with the FDA to evaluate next steps. In a statement, newly minted CEO Weiguo Su, Ph.D., said the company remains confident in the clinical value of surufatinib and that it remains committed to bringing the drug to the U.S.
In spurning surufatinib, the FDA’s oncology department followed a tone that it adopted recently against applications based on data exclusively or primarily generated in China. The FDA in March turned down Lilly and Innovent’s PD-1 inhibitor Tyvyt, or sintilimab, in non-small cell lung cancer after bashing the companies for using a China-only phase 3 trial comparing the drug to old-standard chemotherapy.
Despite Lilly and Innovent’s FDA setback, Su expressed confidence in surufatinib’s application during a conference call in March. During an investor call Monday, the CEO pointed out that the FDA agreed to the initial filing proposal, but he admitted that the landscape is evolving.
For surufatinib's filing, Hutchmed conducted two positive phase 3 clinical trials in China, SANET-p and SANET-ep, both of which stopped early after the drug showed strong efficacy. In SANET-p, surufatinib cut the risk of disease progression or death by 51% over placebo by investigator analysis in pancreatic NET patients. The risk reduction was 67% over placebo in extra-pancreatic NET patients in the SANET-ep trial.
The application package also included a U.S. bridging study with 16 patients in each disease subset, showing relatively similar tumor response rates and disease progression-survival lengths. The FDA evaluated the applicability of the phase 3 studies to U.S. patients, Hutchmed said.
Like Tyvyt, surufatinib’s rejection likely isn’t limited to the single-country pivotal trial but also the trial comparator arms. In both the U.S. and China, Pfizer’s small molecule Sutent has been approved to treat pancreatic NET, and Novartis’ Afinitor is also approved for pancreatic NET and gastrointestinal and lung NET.
Su noted that those two foreign drugs weren’t broadly available when Hutchmed started the surufatinib trials in China. Still, they’ve been approved in the U.S. for years.
When asked about Hutchmed’s next steps, Chief Medical Officer Marek Kania, M.D., said the firm has several options but declined to offer additional details on timing or pending discussions with the FDA. Combining pancreatic and non-pancreatic NETs in one trial “would be the most preferable,” but Su noted that it would be challenging to properly stratify patients with various disease subtypes in a balanced way.
Besides the FDA, drug regulators in EU and Japan are also reviewing surufatinib’s application.
Meanwhile, Hutchmed is also pairing surufatinib with fellow Chinese biotech Junshi Biosciences’ PD-1 inhibitor Tuoyi, or toriplimab, which coincidentally got its own FDA complete response letter Monday. For that drug application, the FDA has requested a quality process change.
In anticipation of an approval for surufatinib, Hutchmed has built a small U.S. commercial team. Kania noted that a global phase 3 trial dubbed FRESCO-2 for the company’s fruquintinib in metastatic colorectal cancer is expected to read out in the second half of the year. A positive readout would trigger applications with the FDA and the European Medicines Agency, he said. In collaboration with Eli Lilly, that drug is sold in China under the brand Elunate.
In addition, a global phase 2 trial of Hutchmed’s AstraZeneca-partnered savolitinib is slated to read out data in non-small cell lung cancer patients following progression on AZ’s Tagrisso. Hutchmed has said a filing based on those data for accelerated approval could be possible. The MET inhibitor won approval in China last year as Orpathys, and AZ is leading the charge outside the country.
“We definitely will continue building and bridging the capabilities into near-term launch readiness efforts as well as utilizing our talents in the most efficient way,” Kania said of the U.S. team.