Opioids, such as morphine, are highly effective in the treatment of moderate-to-severe pain, which could include pain associated with or as a result of back pain, arthritis, cancer and other pain conditions.

Mu-opioid receptors in the gastrointestinal (GI) tract regulate functions such as motility, secretion and absorption. Stimulation of these GI mu-opioid receptors by morphine, or other opioid analgesics, disrupts normal gut motility resulting in non-propulsive contractions of the bowel wall, ultimately delaying transit time of intestinal contents. This is the primary mechanism underlying OIC.

OIC can be distressing for patients, causing a significant burden of illness and reduced quality of life. Some patients receiving long-term opioid treatment for pain would rather endure their pain than the constipation that opioids may cause.

Cubist is developing bevenopran(CB-5945) to treat OIC in patients with chronic non-cancer pain.. This compound is a small-molecule, potent, peripherally-acting mu-opioid receptor antagonist intended to block the adverse effects of opioid analgesics on the GI tract without affecting analgesia.

Clinical Status

During 2010, an initial clinical evaluation of bevenopran (CB-5945) was conducted. The single-dose and multiple-ascending-dose studies of bevenopran enrolled both healthy volunteers and chronic non-cancer pain patients on long-term opioid therapy with OIC. At target therapeutic doses, the compound was well-tolerated and, in the patients with OIC, produced greater increases (over baseline) in weekly average number of spontaneous bowel movements (SBMs) as compared with placebo. The most commonly reported adverse events were dose-dependent and primarily GI related, including abdominal cramping and nausea, the majority of which were of mild severity. There were no serious adverse events reported.

In August 2011, two Phase 2 studies of bevenopran in chronic non-cancer pain patients suffering from OIC were completed. Both Phase 2 trials of bevenopran demonstrated statistically significant and clinically relevant efficacy in patients suffering from OIC and bevenopran was well tolerated in both studies. There was no evidence of drug-related central opioid withdrawal or reversal of analgesia in any of the bevenopran treatment groups across both studies.

As previously announced, Cubist is currently focusing on the completion of a long-term safety trial of bevenopran, which is progressing ahead of schedule.