On June 18, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that the U.S. Food and Drug Administration ("FDA") has granted Fast Track Designation for the development of fruquintinib, for the treatment of patients with metastatic colorectal cancer ("mCRC") who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and, if RAS wild-type, an anti-epidermal growth factor receptor (EGFR) therapy (Press release, Hutchison China MediTech, JUN 18, 2020, https://www.chi-med.com/chi-med-announces-fruquintinib-granted-u-s-fda-fast-track-designation-for-mcrc/ [SID1234561208]).
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Chi-Med is initiating a Phase III registration study, known as the FRESCO-2 study, in refractory mCRC in the U.S., Europe and Japan (clinicaltrials.gov identifier: NCT04322539). FRESCO-2 is expected to start enrolling patients in mid-2020. The U.S. FDA acknowledged that the totality of the fruquintinib clinical data, including the FRESCO-2 study, if positive; the prior positive Phase III FRESCO study demonstrating improvement in overall survival that led to fruquintinib approval for mCRC in China in 2018; and additional completed and ongoing supporting studies in mCRC; could support a New Drug Application ("NDA") for the treatment of patients with mCRC in the third-line setting. The adequacy of the data to support a specific indication will be assessed during the review of a New Drug Application.
About Fast Track Designation
The FDA Fast Track Designation is one of several approaches utilized by the U.S. FDA to expedite development and review of potential medicines for serious conditions and that fulfill unmet medical needs. A potential new medicine may fill an unmet medical need by being the first therapy to address a specific serious condition, offer clinically significant advantages over available therapies, act via a different mechanism of action than available therapies, or have a benefit in patients who are unresponsive to or intolerant of available therapies. Programs that receive Fast Track Designation are entitled to more frequent interactions with the U.S. FDA on drug development plan, as well as eligibility for accelerated approval, priority review, and rolling review.1
About Colorectal Cancer ("CRC") in the U.S.
CRC is the third most common cancer worldwide, causing more than 880,000 deaths in 2018.2 In the U.S., CRC is the fourth most common cause of new cancer cases, but the second leading cause of cancer deaths.3 It is estimated that in 2020, 147,950 people will be diagnosed with CRC and 53,200 people will die from CRC in the U.S.4
About Fruquintinib
Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptor ("VEGFR") 1/2/3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.
Chi-Med retains all rights to fruquintinib outside of China and is partnered with Eli Lilly and Company ("Lilly") in China.
About Fruquintinib in mCRC
Fruquintinib was approved for marketing by the China National Medical Products Administration ("NMPA") in September 2018 and commercially launched by Lilly in late November 2018 under the brand name Elunate. Elunate is for the treatment of patients with mCRC that have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with mCRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).
In December 2017, Chi-Med initiated a multi-center, open-label, Phase Ib clinical study to evaluate the safety, tolerability and pharmacokinetics of fruquintinib in U.S. patients with advanced solid tumors (clinicaltrials.gov identifier: NCT03251378). The study progressed into proof-of-concept trials in 2019, including patients with mCRC and metastatic breast cancer. In February 2020, an End of Phase II (EOP2) meeting was held with the U.S. FDA, and regulatory interactions with the European Medicines Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) are also underway.
Other Fruquintinib Development
Gastric Cancer in China: In October 2017, Chi-Med initiated the FRUTIGA study, a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for second-line treatment of advanced gastric or GEJ adenocarcinoma. The trial is designed to enroll patients who did not respond to first-line standard chemotherapy. Subjects will receive either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. Patients will be randomized at a 1:1 ratio and stratified according to factors such as stomach vs. GEJ tumor type and performance status. The primary efficacy endpoint is overall survival. Secondary efficacy endpoints include progression-free survival (as defined by RECIST 1.1), objective response rate, disease control rate, duration of response, and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers related to the antitumor activity of fruquintinib will also be explored. Additional details about this study can be found at clinicaltrials.gov, using identifier NCT03223376. In June 2020, Chi-Med completed a planned interim data review. Based on the preset criteria, the Independent Data Monitoring Committee (IDMC) recommended that the trial continue.
Immunotherapy combinations: Chi-Med has entered into three collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with programmed death-1 (PD-1) monoclonal antibodies, including with tislelizumab (BGB-A317), Tyvyt (sintilimab, IBI308) and geptanolimab (GB226, genolimzumab).