A new drug for the treatment of severe pain under development by Australian biotechnology company Xenome Limited (“Xenome”) has shown promise for the relief of chronic pain in cancer patients in a Phase II clinical trial.
Relief of pain in cancer patients continues to present a major medical challenge. Patients are usually treated with opioid drugs such as morphine, sometimes in combination with other analgesic drugs. While opioids relieve pain for many patients, they can have the unwanted effects of constipation, nausea, sleepiness and, in isolated cases, the slowing or cessation of breathing. They are also addictive and subject to abuse.
Xenome’s new drug candidate, Xen2174, is a chemically modified, synthetic version of a venom peptide that cone snails use to immobilise prey. It has the potential to overcome some of the disadvantages of opioids and, as a result, could have a significant impact on the quality of life for people suffering from pain.
The results of the cancer pain trial were presented at the 12th World Congress on Pain in Glasgow, UK, attended by thousands of pain researchers and clinical practitioners.
The study investigated a single increasing dose of Xen2174 (from 0.025 to 40 mg) injected into the fluid surrounding the spine (intrathecal administration). It was designed to determine (i) a safe and well tolerated dose of the drug, (ii) the way the body handles Xen2174 (drug pharmacokinetics) and (iii) the patients' pain response to treatment.
The 37 patients enrolled in the trial had a background of chronic pain that was not adequately treated with routine analgesia treatments. Xen2174 was found to be well tolerated by these patients, who had a diversity of cancer history and pain origin and severity at study entry. Evidence of pain relief was seen at most dose levels over the four day observation period and was characterised by rapid onset of action and long-lasting effect.
The majority of adverse events attributable to Xen2174 were assessed as either mild or moderate, with more serious events largely restricted to the highest dose tested.
Analysis of Xen2174 levels demonstrated that standard pharmacokinetic parameters varied in a predictable manner with increasing doses. Peak drug levels and rates of clearance were within acceptable clinical parameters.
“In this study Xen2174 showed a very acceptable side effect profile across a wide range of dose levels, providing a solid basis for continued clinical development. In addition, we saw evidence that a single dose of Xen2174 can relieve pain quickly and for a sustained period” said Dr Ian Nisbet, CEO of Xenome.
The next clinical trial of Xen2174 will be in acute, post-surgical pain, and is due to commence before the end of 2008.
Xenome is a biotechnology company that is focused on the discovery and development of peptide-based therapeutics. The Company's lead product, Xen2174, is a novel conopeptide analogue for the treatment of severe pain. Enrolment into an international phase I/II clinical trial in patients with cancer pain was recently completed and a phase II study in post-operative pain is due to commence in 2008.
Xenome's discovery platform is based on a proprietary library of venom peptides. Late in 2007 Xenome and Amylin Pharmaceuticals entered into a partnership to screen Xenome's library for new drug candidates against metabolic disease targets. Both Xen2174 and the Amylin partnership leverage off Xenome's unique expertise in peptide chemistry and its ability to translate the evolutionary advantages inherent in venom peptides into highly bioactive, drug-like molecules.
Further information can be obtained from the Xenome website (www.xenome.com).
Dr Ian Nisbet
Chief Executive Officer
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