Hutchison MediPharma Limited announces that it has started the first-in-human phase I clinical trial of its anti-cancer drug candidate, Fruquintinib. This follows approval from the State Food and Drug Administration (SFDA) in China. Similar to Hutchison MediPharma’s drug candidate Sulfatinib, the investigational new drug application for Fruquintinib was reviewed through the SFDA’s Green Channel expedited application process. The first patients were dosed on 28 January 2011.

Fruquintinib (HMPL-013) is a novel small molecule that selectively inhibits the tyrosine kinase activity associated with Vascular Endothelial Growth Factor Receptors (VEGFR). Pre-clinical data shows that this compound is a potent suppressor of angiogenesis, an established approach in anti-cancer treatment. In low doses, Fruquintinib has potent inhibitory effects on multiple human tumour xenografts, including some hard-to-treat tumours such as pancreatic cancer and melanoma.

It is differentiated from Sulfatinib and other drugs in this class either on the market or in clinical development by its kinase selectivity in vitro and superior potency in vivo against a variety of human tumour xenografts. Fruquintinib was discovered and developed internally by Hutchison MediPharma.

The phase I clinical study is being conducted in China. The trial is an open-label, dose-escalation study. The primary objective of the trial is to determine the Maximum Tolerated Dose (MTD) and assess the safety and tolerability in patients with advanced solid tumours. The secondary objectives include the assessment of single and multiple dose pharmacokinetics and the evaluation of Fruquintinib’s anti-tumour activity.

Dr Samantha Du, chief executive officer of Hutchison MediPharma, said: “This is further evidence of our capabilities in innovative drug discovery and development and moves another of our pipeline of anti-cancer agents into clinical development. Fruquintinib is highly selective of all three forms of VEGFR, as well as having potent activity against aggressive tumours. Starting the phase I trials takes an additional step toward our goal of developing more effective and safe anti-cancer agents for patients globally.”

Angiogenesis, the process of developing new blood vessels, is critical for tumour cell growth, survival, invasion and metastasis. The Vascular Endothelial Growth Factor Receptors (VEGF) and VEGF receptors (VEGFRs) play a pivotal role in tumour-related angiogenesis, and the VEGF/VEGFR pathway is an important target for anti-angiogenic drug development and tumour therapy.

Inhibition of VEGF signalling in tumour vasculature therefore represents an exciting therapeutic strategy, with the potential to arrest the development of new blood vessels essential for tumour growth and metastasis. Several anti-VEGF agents have shown efficacy in a range of tumour types.

Fruquintinib is a potent, selective, small molecule tyrosine kinase inhibitor of VEGF receptors 1, 2 and 3. In animal studies, Fruquintinib demonstrated broad spectrum anti-tumour efficacy via oral dosing in multiple tumour xenografts.