Completion of enrollment of 416 patients in pivotal Phase III FRESCO trial with fruquintinib in colorectal cancer

Shanghai: Friday, May 13, 2016: Hutchison MediPharma Limited (“HMP”) today announces that it has completed patient enrollment of FRESCO, its Phase III pivotal trial of fruquintinib (HMPL-013) in third-line locally advanced or metastatic colorectal cancer (“CRC”) in China, where an estimated 390,000 new cases of CRC were diagnosed in 2012.

Fruquintinib is a highly selective small molecule drug candidate that has been shown to inhibit vascular endothelial growth factor receptors (VEGFR) 24 hours a day via an oral dose, without known off-target toxicities.  The FRESCO trial is evaluating the efficacy of fruquintinib versus placebo, with all patients receiving best supportive care (“BSC”).  The primary endpoint is overall survival (“OS”).

“Completing enrollment of our first Phase III clinical trial is an important milestone for our company,” said Christian Hogg, Chief Executive Officer of parent company Hutchison China MediTech Limited.  “We believe fruquintinib has the potential to significantly improve outcomes in several types of solid tumors.  While we wait for the FRESCO CRC data to mature over the balance of the year, we are focused on accelerating the ongoing Phase III FALUCA pivotal trial in non-small cell lung cancer (“NSCLC”), and launching additional studies of fruquintinib, including a Phase II study in gastric cancer in combination with paclitaxel, new studies in the U.S., and certain exploratory studies in combination with other oncology agents.”

The FRESCO trial was launched following a 71-patient, randomized, double-blind Phase II trial of fruquintinib as a third-line treatment for metastatic CRC.  The study met its primary endpoint of progression free survival (“PFS”) of 4.73 months for patients receiving fruquintinib versus 0.99 month for the placebo arm, with a hazard ratio of 0.30 (p<0.001), and had no unexpected safety issues.  The positive data resulted in a US$18 million payment to HMP from its partner, Eli Lilly and Company (“Lilly”).

About the FRESCO CRC Trial

FRESCO is a randomized, double-blind, placebo-controlled, multicenter, Phase III pivotal trial in patients with locally advanced or metastatic CRC who have failed at least two prior systemic antineoplastic therapies (i.e. third-line), including fluoropyrimidine, oxaliplatin and irinotecan.  The results of the preceding Phase II trial were presented at the 2015 European Cancer Congress (ESMO; see poster).

The first patient was dosed on December 12, 2014.  A total of 416 patients were randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus BSC; or placebo plus BSC.

The primary endpoint is OS, with secondary endpoints including PFS, objective response rate, disease control rate and duration of response.  Once a pre-specified number of OS events (deaths) have occurred, data analysis will commence.  We expect to publish top-line results at the end of 2016 or in early 2017.

Additional details of the FRESCO study may be found at clinicaltrials.gov, using identifier NCT02314819.

According to the 2012 Chinese Cancer Registry annual report, CRC was 10.3% of the total China cancer incidence, or about 390,000 new cases.

Other Fruquintinib Clinical Development Overview

In addition to CRC, fruquintinib is also in clinical development for lung cancer and gastric cancer.

Lung: In June 2014, HMP initiated a second proof-of-concept (“POC”) Phase II trial of fruquintinib in third-line NSCLC patients in China.  91 patients received fruquintinib plus BSC or placebo plus BSC at a 2:1 ratio.  Top-line results demonstrated that the trial succeeded in meeting the primary efficacy endpoint of PFS, with no unexpected safety issues.  Detailed results will be presented at an upcoming scientific conference in 2016.  The positive results of this trial triggered a US$10 million payment from Lilly and the initiation of FALUCA in December 2015, a 520-patient Phase III pivotal study of fruquintinib in third-line NSCLC patients in China.  Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02691299.

Gastric: HMP is nearing completion of a Phase Ib dose-finding study of fruquintinib, in combination with paclitaxel, in second-line gastric cancer patients and plans to initiate a Phase II POC study in 2016.  Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02415023.

HMP receives reimbursement for costs associated with clinical development in China from Lilly according to a pre-specified cost-sharing rate.