Locus Pharmaceuticals' new drug targets drug-resistant tumours
anticancer drug that could prove effective against drug resistant
tumours after the small molecule cleared the 30-day review period
by the FDA for its Investigational New Drug (IND) application
Drug resistance is a major complication in cancer chemotherapy and accounts for the failure of chemotherapy to cure the majority of cancer patients. Drug resistance has been described as "the single most common reason for discontinuation of a drug."
Drug resistance exists in two forms: acquired resistance, in which a drug is initially beneficial but becomes ineffective over time and intrinsic resistance, in which the drug is ineffective from the outset.
It is hoped that this new drug can prove more effective in treating types of cancer. The drug candidate LP-261, works by binding to tubulin in a novel way, specifically at the colchicine site to induce G2/M arrest and block cell division, the mechanism by which cancer cells proliferate
This drug is distinguished by its anti-tumour and anti-angiogenesis combination mechanism, 100 per cent oral bioavailability and potential to treat resistant tumours.
Tubulin targeting agents make up one of the largest markets in the pharmaceutical industry. There are three recognised binding sites for pharmacologic agents on tubulin: the taxane, vinca and colchicine sites.
All of the approved tubulin drugs target either the taxane or vinca sites and are parenterally administered.
As a result, LP-261, being orally administered and with a novel colchicine binding mode, would offer a new approach to this validated target.
In preclinical studies, LP-261 demonstrated broad anti-tumour activity in vitro and, after oral administration, in vivo, including tumour regression in xenograft models of several major solid tumour types.
In addition, the compound has demonstrated anti-angiogenic effects in certain angiogenesis models.
Importantly, LP-261 has also been shown to be effective in taxol-resistant cells, vinca-resistant cells, and primary leukaemia cells isolated from Gleevec-resistant patients. LP-261 does not appear to be a substrate for MDR pumps.
The protocol for the Phase I is now before Institutional Review Boards (IRB's) at the sites selected for the trial and clinical supplies are being prepared.
The Phase I will be an open-label, dose-escalation study to evaluate the safety and pharmacology of the drug in patients with advanced tumours.