Pfizer’s Sutent and Novartis’ Afinitor and Lutathera are all approved to treat certain neuroendocrine tumors, but no one drug can cover all types. Hutchison China MediTech (Chi-Med) is hoping to change that—and now it has a late-stage clinical win under its belt.
Chi-Med’s self-discovered surufatinib stalled cancer progression by a median 9.2 months among Chinese patients whose neuroendocrine tumors (NETs) originated outside of the pancreas. That's significantly longer than the 3.8 months observed with placebo in a phase 3 study, investigators reported at the annual European Society for Medical Oncology (ESMO) meeting.
The data come from a study called SANET-ep, which the company stopped in June after an interim analysis showed it had already met its primary endpoint. The results are particularly positive because they were “achieved in patients regardless of tumor origin and in patients who received prior systematic treatment for their disease,” Jianming Xu, the study’s co-lead investigator, said in a statement.
Chi-Med expects to file a new drug application with Chinese authorities this year and has already built a dedicated medical and sales team of about 80 people, with plans to expand to 250 to 300 next year, Chi-Med CEO Christian Hogg told FiercePharma.
If successful, surufatinib would fill a blank in China. Currently, Pfizer’s VEGFR drug Sutent and Novartis’ mTOR inhibitor Afinitor are available on China’s national formulary, but they’re only approved to treat pancreatic NETs. All told, Chi-Med pegs the Chinese NET market at about $100 million to $120 million annually, as the non-pancreatic NET population is about four times that of pancreatic.
Chi-Med isn’t just eyeing the extrapancreatic market in China. But to achieve surufatinib’s ambition of becoming the first targeted therapy to treat patients with all types of NETs, it will have several hurdles to jump.
First, in the SANET-ep trial, the progression-free survival number reported by an independent image review committee was only 7.4 months for the Chi-Med drug, compared with the 9.2 months reported by the trial investigators. Hogg attributed the difference to the nature of NETs and the higher proportion of patients who got loco-regional therapy in the surufatinib arm, both of which could make the blinded independent analysis less accurate.
“It’s about the pathology of the tumor, how it shows up on a CT scan,” he said. “It’s known by the regulatory authorities, that’s why the Chinese [Center of Drug Evaluation] did not require blinded independent clinical assessment as a primary or a secondary endpoint.” And the imaging doesn’t provide other information on signs that indicate efficacy, he added.
What’s more, usage of loco-regional therapy, such as chemo or radiotherapy, directed at the tumor could make it challenging to evaluate new lesions—tumor progression, in other words—in those organs, Hogg said.
But surufatinib’s data also appear weaker than Afinitor’s historical results. In its own global Radiant-4 study on patients with nonfunctional, locally advanced or metastatic NET of GI (excluding pancreatic) or lung origin, Afinitor plus best supportive care kept tumor progression at bay for a median of 11.0 months, versus 3.9 months in the control arm. Based on that data, Afinitor already boasts an approval to treat both types of NETs.
Such cross-trial comparisons can be problematic, though. NET disease is better known and more likely to be diagnosed early in the U.S. compared with China. Generally, Afinitor and Lutathera studies have mostly enrolled patients with grade 1 tumors, Hogg explained, but in the SANET-ep study, about 84% of patients had more serious grade 2 tumors.
Novartis' newer NET drugs have become a growth point since its older med Sandostatin went off patent. Last year, Afinitor sold $1.56 billion worldwide, and Novartis attributed the drug’s 2% growth partly to its neuroendocrine tumor indication in the U.S.
Meanwhile, its radiotherapy Lutathera racked up $109 million in second-quarter sales as Novartis continued to tout its blockbuster potential. The drug won FDA approval in the broad gastroenteropancreatic NET indication last year.
Chi-Med has ambitions outside China as well. At ESMO, the company reported data on 12 patients with heavily treated pancreatic NET from a U.S. phase 1/1b study. “If you look closely at that data, you’ll see that surufatinib does very well in patients that have already failed on Afinitor,” Hogg said. “That [speaks to surufatinib’s] global potential as an additional therapy that acts in a different way.”
Surufatinib inhibits VEGFR and FGFR to cut off blood flow to tumors, and it also acts on a receptor called CSF-1R, which regulates tumor-associated macrophages that hide cancer cells from the body’s immune response.
The global phase 3 SANET-p study in pancreatic NET is scheduled to start first quarter next year, and because there’s more evidence showing these patients respond well to targeted therapy, Hogg said that study is less risky than SANET-ep.
Based on the extrapancreatic data now available in China, Chi-Med is trying to figure out its registrational strategy in the U.S. and Europe. “Initially, it was thought to be pancreatic NET is the way to go,” he said. “Maybe now we’ll have to go parallel.”