BioWorld International Correspondent

LONDON - CeNeS Pharmaceuticals plc announced positive preliminary results in the pivotal Phase III European trial of its morphine metabolite M6G (morphine-6-glucuronide) in more than 500 patients with postoperative pain, showing equal analgesic effect but reduced incidence of nausea and vomiting.

CEO Neil Clark told a teleconference that the "very good" results represented a major step forward for CeNeS. "M6G has been a central part of the company's activities in the past five to six years. We have made great progress to deliver this drug and have now shown it provides similar pain relief to morphine, with far less nausea and vomiting."

Clark said clinicians who worked on the study agreed CeNeS is delivering a new drug profile and that the reduction in nausea and vomiting is clinically significant.

The quality of the Phase III data would now enable the company to look for partners to move forward to filing. "These results mean we will be able to find good partners," Clark said. In the next few years, that could transform Cambridge-based CeNeS, allowing it to bring forward other products.

As is crucial for a novel pain product, the trial results show that M6G is as good as morphine in terms of analgesia achieved in patients up to 48 hours after major abdominal surgery. That is the first trial of M6G in which the analgesia was self-administered by patients.

The one small fly in the ointment is that the study did not reach statistical significance in the primary endpoint of overall reduction in nausea and vomiting. There was an overall reduction of 27 percent in the incidence of nausea and vomiting in the M6G arm, just missing significance. "That's frustrating, but we are confident on the other statistics," said Clark.

Patients receiving M6G experienced a 28 percent reduction in the severity of postoperative nausea and vomiting and the incidence of vomiting in the M6G arm was 32 percent lower, with both those results showing significance. Postoperative nausea and vomiting is rated among patients as one of the most distressing aftereffects of surgery.

The trial confirmed that M6G's safety profile is similar to morphine. Study leader Alexander Binning, consultant anesthetist at Western Infirmary, Glasgow said, "These data demonstrate that M6G is equivalent to morphine in its analgesic properties. It also shows a clear improvement in managing postoperative nausea and vomiting."

A fuller data set is due in the next few weeks that will show how much analgesia patients self-administered and the amount of antiemetics used.

Clark said CeNeS intends to file an IND for M6G with the FDA in the next few weeks. The company is in discussion with a number of potential partners. Clark said the strategy in Europe is to have a partner before filing. "Just missing statistical significance does impact how regulators will view it. Maybe we do need an additional Phase III/IV trial and should wait for a partner to guide us," Clark said.

The company will need to conduct a Phase III trial in the U.S., and Clark said the results of the European trial have de-risked that process.