Shanghai: Friday, November 6, 2015: Hutchison MediPharma Limited (“HMP”) today announces that it has initiated the Phase I clinical trial of sulfatinib (HMPL-012) in the United States. Its U.S. Investigational New Drug application was submitted and cleared earlier this year and the first patient was dosed on 4 November 2015. HMP is also planning to initiate two Phase III registration studies for the treatment of neuroendocrine tumors (“NET”) and a Phase Ib study for the treatment of thyroid cancer with sulfatinib in China by the end of 2015.
This Phase I dose escalation study is to assess the safety and tolerability of sulfatinib in U.S. patients with advanced solid tumors. A U.S. Phase II study in NET is expected to be initiated based on the conclusion of this Phase I dose escalation study.
Sulfatinib is an oral drug candidate that selectively inhibits the tyrosine kinase activity associated with the vascular endothelial growth factor receptor (“VEGFR”) and fibroblast growth receptor (“FGFR”), a receptor for a protein which also plays a role in tumor growth. In a Phase I clinical trial in China focusing on NET patients, sulfatinib’s objective response rate among the 18 efficacy-evaluable NET patients was 44.4%. By comparison, sunitinib and everolimus, the two approved single agent therapies for pancreatic NET, achieved objective response rates of less than 10% in their pivotal clinical trials. Furthermore, NET responses to sulfatinib have been observed to improve gradually with time. Results of the Phase I trial in China will be reported at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in November 2015 and will be made available at www.hmplglobal.com/en/publications/ .
Sulfatinib is the first oncology candidate that HMP has taken through proof-of-concept in China and expanded to a U.S. clinical study without a partner.
Overview of sulfatinib clinical development
In addition to the U.S. Phase I clinical trial, HMP is conducting or in the process of initiating four clinical trials in China.
In October 2014, HMP initiated a multi-center, single-arm, open-label Phase Ib/II study in broad spectrum NET patients (pancreatic, gastrointestinal, liver, lymph and lung, among others) in China to further evaluate the efficacy, safety, tolerability, and pharmacokinetic characteristics of sulfatinib. This study, projected to enroll approximately 80 patients, is near to completion of patient enrolment. Results to date of this open-label Phase Ib study appear generally in line with the positive results from the Phase I study.
Encouraged by these results, HMP now plans to start two Phase III registration studies in China by the end of 2015, one in pancreatic NET patients and a second in advanced carcinoid (non-pancreatic) NET patients.
HMP plans to initiate a Phase Ib study in China to evaluate the safety, pharmacokinetics and efficacy of sulfatinib in patients with both medullary and differentiated thyroid cancer by the end of 2015. Sulfatinib’s VEGFR/FGFR1 inhibition profile is believed to have strong potential in second-line thyroid cancer patients, particularly in China where there are few safe and effective treatment options for this patient population. HMP plans to enroll approximately 50 patients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer or medullary thyroid cancer into this study, with approximately 25 patients in each tumor type.
NET arises from neuroendocrine cells and develops predominantly in the digestive or respiratory tracts but can also occur in many areas of the body. Diagnosing NET is difficult due to the small tumor size and diverse occurrence with patients showing varied or no symptoms. As a result, it has been difficult to accurately estimate the number of NET incidences per year. There were approximately 19,000 new cases of NET and a cumulative prevalence of approximately 141,000 cases in the United States in 2014.