CAMBRIDGE, United Kingdom, July 2, 2003 (PRIMEZONE) -- CeNeS Pharmaceuticals plc (LSE:CEN) today announced that it has finalised its plans for the Phase III trials of M6G (morphine-6-glucuronide) for the treatment of post-operative pain and the early Phase II trials of CNS 5161, its novel compound for the treatment of neuropathic pain.
M6G - for the treatment of post-operative pain
M6G has commenced an initial Phase III trial, which we anticipate will complete in mid-2004. The trial will seek to recruit 168 patients in hospitals in three European countries. The patients will be suffering post-operative pain following knee surgery carried out under spinal anaesthesia. The prime objective of the study is to compare the analgesic efficacy and duration of action of a range of doses of M6G given intravenously, compared with placebo. Subsequently, a second Phase III trial is then planned and it is expected that an initial European product filing could be made in late 2005.
Phase II clinical trials have already shown that M6G produces equivalent analgesia to morphine to combat post-operative pain. Additional clinical studies in post-operative nausea and vomiting have also shown that M6G reduced the incidence of nausea and vomiting by more than 50% when compared directly with morphine. These data have confirmed that M6G induces equivalent analgesia to morphine combined with an improved side effect profile. In particular M6G appears to cause a significantly lower frequency and severity of nausea and vomiting than morphine. If CeNeS is able to confirm in larger phase III clinical trials that M6G causes fewer side effects than morphine, but has equal analgesic efficacy, then this could produce an attractive alternative for patients and healthcare providers.
CNS 5161 -- for the treatment of neuropathic pain
CeNeS has finalised plans for an extended Phase II trial of CNS 5161, a novel compound for the treatment of neuropathic pain. The Phase II trial will commence later in 2003 and results are expected in mid-2004. An initial phase II study has been completed in 10 patients with chronic intractable neuropathic pain. This study demonstrated that 0.25mg of CNS 5161 gave statistically significant pain relief. The drug was well tolerated by the patients.
Further updates on the progress of these two trials will be given in due course. CeNeS currently has cash reserves to complete the first M6G Phase III trial and the planned CNS 5161 Phase II trial referred to above. After allowing for these ongoing clinical trial expenses, CeNeS plans to have sufficient funds for ongoing operations until the end of 2005.
Neil Clark, Chief Operating Officer and Financial Director of CeNeS commented, "CeNeS is excited by the potential of its later stage clinical candidates. The CeNeS Board is continuing to investigate other opportunities to enhance shareholder value."
This news release contains forward-looking statements that reflect the Company's current expectation regarding future events. Forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors including the success of the Company's research strategy, the applicability of the discoveries made therein, the successful and timely completion of clinical studies and the uncertainties related to the regulatory process.
Notes to Editors:
CeNeS is a biopharmaceutical company specialising in the development and commercialisation of drugs for pain control. The company has development assets targeting pain and has a portfolio of carried interests in assets that it has divested. The company is based in Cambridge, England. For further information visit www.cenes.co.uk.
M6G
M6G, a natural metabolite of morphine, is in development by CeNeS for the treatment of moderate to severe pain. Morphine is a highly effective analgesic that has been used for many years despite the unpleasant side effects of nausea and vomiting and the potential dangers of respiratory depression.
M6G has undergone several Phase II clinical trials with more than 450 patients receiving M6G. The most recent Phase II trials were designed to establish the analgesic effects of different doses of M6G administered at different times compared to a standard morphine treatment regime. Phase III efficacy studies are currently being planned: a pivotal, dose-ranging placebo controlled study is scheduled to commence as a multi-centre study in Europe in 2003 in patients undergoing knee replacement surgery with spinal anaesthesia. It is planned that this will be followed by a second Phase III trial in Europe comparing M6G and morphine treatment in patients with postoperative pain following gastrointestinal and gynaecological surgery. Side-effect profiles of M6G will be investigated in both studies. If these trials are successful, then M6G will be on target to be launched in Europe in 2005/6.
Opiate Analgesia
Analgesia is the process of pain-relief and any pain-relieving drug is called an analgesic. The most potent known class of analgesics are the opiates, derived from the opium poppy, which confer a high degree of pain-relief for severe pain. Opiates, like morphine and codeine, act centrally in the brain in an area called the periaqueductal grey area where they mimic the actions of neuromodulators called endogenous opiates and 'switch off' the sensation of pain centrally.
The markets for M6G
M6G has potential as an analgesic for two types of pain, post -operative pain and chronic pain, both of which are currently treated with morphine.
For post-operative pain morphine is often used as the first line analgesic in many of the 95 million operations performed in the USA and Europe each year. Estimated annual sales of morphine in this market are (Pounds) 400m (source: IMS and Front Line Pain Management Report, 2001). However, the undesirable side effects of morphine include nausea, vomiting, respiratory depression and sedation. M6G is likely to offer significant clinical benefits to morphine in the treatment of post-operative pain due to the reduced incidence and severity of some of these side effects, whist offering equal analgesic efficacy.
Morphine is also used frequently to treat many of the 2.7 million patients who develop cancer each year in the USA and Europe. M6G could compete in this (Pounds) 600m morphine market because M6G could potentially lead to a reduced incidence and severity of nausea and vomiting compared with morphine and so could improve patient well-being and quality of life.
CeNeS is initially developing M6G for the treatment of post-operative pain, with phase III studies planned for 2003. CeNeS plans to also develop M6G for the treatment of chronic pain such as cancer pain.
CNS5161
CNS 5161 is a blocker of the N-methyl-D-aspartate (NMDA) ion channel associated with the glutamate receptor. Excessive activation of the glutamate system has been implicated in the pathophysiology of neuropathic pain. These glutamate receptors are found throughout the nervous system and animal models have helped researchers uncover evidence that in the spinal chord these receptors share a special relationship with neuropathic pain. It appears that continuous activation of the NMDA ion channel in glutamate receptors reorganises pain-sensing circuits and leads to the super-sensitive quality of neuropathic pain. Agents that block these receptors, also block the pain in animals and humans.
The markets for CNS 5161
Neuropathic pain is a chronic painful condition associated with injury to the nervous system and often associated with diseases such as diabetes, herpes zoster, AIDS and cancer. CNS 5161 is being developed targeting a poorly treated population of around 8 million patients suffering from neuropathic pain in the major pharmaceutical markets. The neuropathic pain market is estimated at being worth $1.7 billion worldwide.