Successful Phase III results announced on Lead Product M6G
Successful Phase III results announced on Lead Product M6G Phase III trial in Europe demonstrates M6G's benefit compared to morphine in the treatment of post-operative pain
CAMBRIDGE, 20th February 2007 - CeNeS Pharmaceuticals plc (AIM: CEN), the Cambridge based biopharmaceutical company, today announces preliminary results of the pivotal Phase III trial (M6G022) of M6G (morphine-6-glucuronide) in over 500 patients with post-operative pain. This study is the largest carried out to date with M6G and has delivered very strong results with M6G showing benefits over morphine in the management of post operative patients. M6G022 demonstrates the unique product profile of M6G with equal analgesia to morphine but with reduced nausea and vomiting.
Phase III trial results
1. M6G matches morphine for analgesic effect
Importantly for a novel pain product, the trial results unequivocally show that M6G is as good as morphine in terms of analgesia achieved in patients up to 48 hours post-operatively. Successful achievement of this first primary endpoint supports data from previous clinical trials of M6G and is an essential component in the product profile of M6G.
2. M6G shows significant reduction in post-operative nausea and vomiting compared to morphine
The trial results confirm the excellent potential of M6G as an analgesic with a clinically significant improved side effect profile compared to morphine. The study results show that patients receiving M6G experienced a 28% reduction in the severity of post-operative nausea and vomiting (PONV) in the key 6 - 24 hours after treatment (statistically significant, p=0.018).
In addition, the incidence of dry retching/vomiting in the M6G arm compared to the morphine arm in the 24 hour period after treatment was reduced by 32% (statistically significant, p= 0.044). The incidence and severity of post-operative nausea in the M6G arm was 27% less than that observed in the morphine arm in the period 6 - 24 hours after treatment. This was the second primary endpoint and approached statistical significance (p=0.052).
Morphine formulations are the gold standard treatment for the relief of moderate to severe post-operative pain. A limitation of morphine treatment is often the unpleasant side effects experienced, of which nausea and vomiting are the most common. PONV is rated among patients as one of the most distressing after-effects of surgery and reduces their quality of life.
M6G's lower propensity to cause nausea and vomiting in the post-operative period strongly supports CeNeS' belief in the potential of M6G as a novel product for the treatment of post-operative pain with clear advantages over morphine.
The global market was valued at $1 billion in 2000 and growing at a rate of 6-7%.
3. Safety profile/adverse events
The trial confirmed that M6G's safety profile is similar to morphine. Aside from nausea and vomiting, the adverse events reported were at levels similar to those experienced by patients receiving morphine in a post-operative setting.
Dr Alexander Binning M.B. Ch.B. FRCA, Consultant Anaesthetist at Western Infirmary, Glasgow and Principal Investigator on M6G022, commented: "These data demonstrate that M6G is equivalent to morphine in its analgesic properties. It also shows a clear improvement in managing post-operative nausea and vomiting and has significantly advanced the development of M6G as a potential new drug."
Neil Clark, Chief Executive of CeNeS, commented: "These results strongly confirm our belief in the excellent potential of M6G as a novel product for post operative pain. The quality and breadth of the data contained in this large study support M6G's anticipated product profile. With the completion of this large European study CeNeS is confident that it has a substantial data package that differentiates M6G from morphine which will be attractive to a larger pharma partner to licence. CeNeS intends to file an IND (Investigational New Drug application) for M6G with the FDA in the next few weeks. The data from this trial will also be submitted for publication in a scientific journal in due course.
The successful completion of this large, pan-European study demonstrates the excellence of our clinical development team and the quality of the clinical trial protocol. Following this success we now look forward to working with partners to register M6G as a product in major markets."
M6G022 Study Design The study involved 24 centres in six European countries and recruited 517 patients. The study was designed primarily to provide key information on a comparison of effective intravenous pain management regimens of M6G or morphine treatment for a minimum of 24 hours (and up to 48 hours) following major abdominal surgery. Morphine is generally accepted as the "gold standard" drug for use in these circumstances. Initial pain management was achieved by administration of a loading dose and titration of either M6G or morphine to achieve acceptably low levels of pain for the patient to go onto the ward. In the ward, pain management treatment was achieved by patient controlled analgesia (PCA), whereby the patient was allowed to self administer a dose of M6G or morphine as required to control their pain. The study was randomised and double blind so that neither patient nor carer was aware of which treatment was being administered. The main purpose of the study was to demonstrate statistically that:
- treatment with either M6G or morphine, particularly during PCA, results in similar levels of pain management; and
- effective analgesic treatment during PCA results in lower levels of nausea and vomiting in patients receiving M6G compared to those receiving morphine.
In addition, other important side effect, efficacy and safety features were determined throughout the study.
M6G Commercial Strategy CeNeS has commissioned a number of qualitative market research studies on M6G, which have been carried out by independent market research agencies with extensive experience of the pain market. The outcomes of these studies, involving interviews with clinicians and payers in major markets, support CeNeS' view that potential global peak sales of M6G in post-operative pain could reach $400 million. This is underpinned by a clear need for an improvement on existing drugs for moderate to severe pain which do not offer the attractive M6G profile of morphine-like pain relief with reduced side effects.
CeNeS believes that the positive results announced today from M6G022 will enable the Company to secure valuable licensing agreements for Europe and North America with partners able to offer strong specialist marketing, sales and distribution capabilities within the hospital sector. CeNeS intends to explore all opportunities to capture value from any such licensing agreement including the possibility of retaining promotion or co-promotion rights within certain territories.
CeNeS is in discussion with a number of potential partners and is confident that the positive results from M6G022, together with the extensive package of clinical, non-clinical and manufacturing data provides an attractive package for out-licensing.
There will be a teleconference briefing for analysts and investors today at 9.00am. For details please contact Mo Noonan on +44 (0) 207 831 3113 or firstname.lastname@example.org.
For more information please contact: CeNeS Pharmaceuticals plc Neil Clark, CEO Tel: +44 (0)1223 266 466
JM Finn Geoff Nash Tel: +44(0) 207 628 9688
Financial Dynamics Ben Brewerton/Emma Thompson Tel: + 44 (0) 207 831 3113
About CeNeS Pharmaceuticals CeNeS is a biopharmaceutical company specialising in the development and commercialisation of drugs for pain control, sedation and other CNS disorders such as Parkinson's disease. The company is based in Cambridge, England. For further information visit the CeNeS web site: www.cenes.com
About M6G Morphine formulations are the gold standard treatment for the relief of moderate to severe post-operative pain. A limitation of morphine treatment is often the unpleasant side effects experienced, of which nausea and vomiting are the most common. PONV is rated among patients as one of the most distressing after-effects of surgery and reduces their quality of life.
The active potent metabolite of morphine, morphine-6-glucuronide (M6G), may offer therapeutic advantages over morphine in having an equivalent analgesic effect, but with a reduced tendency to cause nausea, vomiting and respiratory depression. Phase II and III clinical trials have shown that M6G given intravenously produces equivalent analgesia to morphine to combat post-operative pain. Studies have also shown that M6G reduced the incidence of nausea and vomiting when compared directly with morphine. Other studies published recently in the scientific literature demonstrate that M6G also reduces respiratory depression compared to morphine.
Posted: February 2007