HONG KONG – Hutchison China Meditech Ltd. (Chi-Med) is preparing for the next step after surufatinib achieved its primary endpoint in a phase III SANET-ep study in extra-pancreatic advanced neuroendocrine tumors (NETs) in China.

"We are preparing for the potential NDA submission in China for surufatinib ... by the end of the year," Christian Hogg, CEO of Chi-Med, told BioWorld.

Chi-Med presented data this week at the 2019 European Society for Medical Oncology (ESMO) Congress showing that surufatinib reduced the risk of progression or death by 67% in patients as compared to patients on placebo control.

"The SANET-ep results showed that surufatinib meaningfully benefited Chinese patients with progressive, advanced extra-pancreatic NET, across multiple measures of efficacy and was generally well-tolerated," said Jianming Xu, co-lead investigator for the SANET-ep study.

Xu added that those positive results were achieved in patients regardless of tumor origin and in patients who had received prior systematic treatment for their disease.

According to Hogg, surufatinib (HMPL-012, formerly known as sulfatinib) is an oral small-molecule angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with VEGFR and fibroblast growth factor receptor (FGFR). Those two factors inhibit angiogenesis and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages and promotes the body's immune response against tumor cells.

"Both in China and globally, options are limited for NET patients whose tumors originate outside of the pancreas. These patients account for over 90 percent of all NET cases," said Lin Shen, co-lead investigator for the SANET-ep study.

Thus, the SANET-ep results represent an important potential advancement in clinical practice for those patients. But that's not the only indication for which Chi-Med has been studying surufatinib.

At ESMO, Chi-Med also presented data on the safety and tolerability of surufatinib from an ongoing U.S. phase Ib study in pancreatic NET patients who have progressed on Sutent (sunitinib, Pfizer Inc.) or Afinitor (everolimus, Novartis AG) treatment.

"We plan to have an end-of-phase II meeting with the U.S. FDA by end [of] 2019 to discuss U.S. development and registration study design and plans. We plan to start a registration-intent study [for either pancreatic NET or SANET-ep] globally [U.S. and EU] in the first half of next year," said Hogg.

Earlier this year, Chi-Med also began a phase IIb/III study of the candidate as a second-line therapy in patients with unresectable or metastatic biliary tract cancer (BTC), whose disease progressed on first-line chemotherapy. (See BioWorld, April 5, 2019.)

In the latter study, the primary endpoint is overall survival. Secondary outcomes include measures of tumor control such as progression-free survival, objective response rate, disease control rate and duration of response, quality of life, tumor biomarkers and safety.

For that study, the first patient in China was dosed in the first quarter of 2019. The company sees great potential in that territory. According to Chi-Med, the China market alone has almost a quarter (24%) of the world's cancer patient population.

"China's biotech industry has grown significantly over the last few years, thanks to a more favorable external environment driven by the regulatory reform as well as access to capital market and talent," said Hogg.

"The last two years have seen significant regulatory reform to accelerate drug approval and expand reimbursement coverage." He cited factors such as the mainland Chinese government issuing favorable tax policies, talent incentive programs and special public research and development subsidies to drive innovative drug development.

"In addition, the Hong Kong Stock Exchange has opened a new chapter for pre-revenue biotechs, which has been a great catalyst to create a biotech ecosystem in China and Asia," he said.

Chi-Med has eight drug candidates in development. Five of those are in global development, including surufatinib.

"We are also planning to study surufatinib in combination with PD-1 inhibitors in a variety of solid tumors," said Hogg. "VEGF plays an import role in solid tumor progression, and we are beginning to see that it can be synergistically combined with other drugs such as PD-1 inhibitors."

The other candidates are fruquintinib (a potential best-in-class small-molecule selective VEGFR 1/2/3 inhibitor); savolitinib (a c-MET inhibitor); and two candidates that target a key protein in B-cell targeting, namely HMPL-523 (a selective Syk inhibitor) and HMPL-689 (a PI3K-delta inhibitor).

"Looking ahead, we target registering multiple NDAs in the coming two or three years, covering savolitinib, surufatinib and fruquintinib, as well as registration studies with our hematological cancer assets," said Hogg.

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