Dynogen's Oral Prokinetic Drug, DDP733, Shown to Reduce Reflux in Phase 1B Study
DDP733 is an orally administered prokinetic which Dynogen is developing as a treatment for both NGERD and irritable bowel syndrome with constipation (IBS-c). In the Phase 1b translational medicine reflux study, 28 healthy volunteers were given a high fat meal to induce gastroesophageal reflux. Subjects were randomized into this crossover study on a 1:2:1 basis to receive one of three dose levels of DDP733 (0.5 mg, 0.8 mg, or 1.4 mg) and placebo in random order. Reflux events were measured by intraesophageal impedance (determining the height and duration of a reflux episode using electrical resistance). The 0.5 mg dose of DDP733 achieved statistical significance over placebo on the primary endpoint of reduction in the number of reflux events. Trial results also demonstrated that the drug was safe and well tolerated. Dynogen plans to initiate a Phase 2 study of DDP733 in GERD patients in 2008.
"There are no approved prokinetic agents for NGERD available today. As a result, a large number of NGERD patients taking traditional acid suppression therapies still suffer from reflux at night. We believe that DDP733 will address the underlying motility abnormalities inherent to the disease," said Dr. Suhail Nurbhai, MRCP, Vice President of Clinical Development at Dynogen. "The efficacy signal detected in our proof of concept trial strongly suggests that DDP733 will provide a safe new therapeutic option for these poorly served patients. Presenting these results at ACG underscores the importance of our findings and the promising data supports moving this program into Phase 2 development next year."
In February of this year, Dynogen announced positive results from its Phase 2 study of DDP733 in IBS-c, with a statistically significant improvement over placebo in the clinical endpoint of Overall Subject Global Assessment of IBS. A Phase 2b study of DDP733 in IBS-c is expected to begin in the fourth quarter of this year.
DDP733 is an oral, partial agonist of the serotonin type 3 receptor (5-HT3). Serotonin is a neurotransmitter that is known to be involved in the control of the gastrointestinal (GI) system. Preclinical studies of DDP733 established the compound's prokinetic properties (the ability to promote the motility of the GI tract). Dynogen's preclinical studies have also shown that DDP733 is minimally absorbed by the cells lining the gastrointestinal tract and, as a result, more of the product candidate remains available at the desired local site of action. A recently completed Phase 2 study of the candidate as a treatment for IBS-c demonstrated an overall clinical response rate of 54% in patients receiving a dose of 1.4 mg t.i.d. compared to a 15% clinical response rate for patients receiving placebo, and the drug was also well-tolerated. Previous clinical studies of the compound have demonstrated favorable safety and pharmacokinetic profiles. Dynogen has exclusive rights under issued U.S. and European patents related to the use of DDP733 as a treatment for NGERD.
About Nocturnal Gastroesophageal Reflux Disease (NGERD)
Gastroesophageal reflux disease (GERD) is a chronic condition that afflicts approximately 20 percent of adults in the United States. Persistent heartburn is the most common symptom of GERD, but patients may also experience acid regurgitation into the esophagus, dyspepsia (stomach pain) and dysphagia (difficulty swallowing). GERD affects all age groups, although the incidence increases markedly after the age of 40. If left untreated, complications of GERD can include esophageal erosions or ulcers and abnormal narrowing of the esophagus. Years of chronic heartburn, left untreated, can lead to esophageal cancer, currently the fastest growing cancer in the United States. NGERD is the occurrence of GERD at night, typically while lying down to sleep. Approximately 10 percent of adults in the United States suffer from nighttime symptoms of GERD. Symptoms associated with stomach reflux are exacerbated by the lack of assistance from gravity while lying recumbent. NGERD is commonly associated with a higher risk and a higher degree of esophagitis; acid remains in the esophagus for prolonged periods because there is less swallowing and less saliva produced to neutralize the acid. It is estimated that approximately one-third of patients suffering from NGERD experience symptoms that are uncontrolled by current therapies.
About Dynogen Pharmaceuticals, Inc.
Dynogen is a clinical-stage company developing a portfolio of treatments for gastrointestinal and genitourinary disorders. The Company is focused on large and untapped markets in disease areas that severely impair a patient's quality of life, such as irritable bowel syndrome, gastroesophageal reflux disease and overactive bladder. The Company leverages its development expertise to identify promising clinical compounds and rapidly advance them towards registration. www.dynogen.com
Posted: October 2007