Dynogen's Prokinetic Drug, DDP733, Enters Phase 2b For Irritable Bowel Syndrome With Constipation

Main Category: Irritable-Bowel Syndrome
Also Included In: Clinical Trials / Drug Trials
Article Date: 09 Nov 2007 - 13:00 PDT

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Dynogen Pharmaceuticals, Inc. announced that the first patients have been dosed in a Phase 2b trial of DDP733 (pumosetrag) as a treatment for irritable bowel syndrome with constipation (IBS-c). This DDP733 Phase 2b trial is a randomized, double-blind, placebo controlled study that is enrolling female patients with IBS-c at multiple centers in the U.S. and Canada. The study is assessing efficacy using the Overall Subject Global Assessment (OSGA) of relief of IBS symptoms, as well as the safety and tolerability of the drug.

DDP733 is an oral prokinetic drug which Dynogen is developing as a treatment for both IBS-c and nocturnal gastroesophageal reflux disease (NGERD). In February of this year, Dynogen announced positive results from its Phase 2a study of DDP733 in IBS-c, with a statistically significant improvement over placebo in the clinical endpoint of OSGA of IBS. In the study, DDP733 achieved a statistically significant overall benefit in the overall clinical response rate with a 54% response rate in patients receiving the 1.4 mg t.i.d. dose of the drug compared to a 15% response rate for patients receiving placebo. The OSGA is a clinical endpoint which the FDA has previously accepted as a registration endpoint for IBS-c.

"Initiating this Phase 2b IBS-c study is an important step in the continued clinical development of DDP733," said Dr. Suhail Nurbhai, MRCP, Vice President of Clinical Development at Dynogen. "Based on the strong efficacy signal obtained in our Phase 2a study and the demonstrated safety profile of the compound, we believe DDP733 has the potential to be a safe and effective treatment for the nine million patients who suffer from this painful and debilitating disease and for whom there is currently no available therapy."

About DDP733

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.

Dynogen also announced positive results from its Phase 1b translational medicine reflux study of DDP733 where 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 from both studies demonstrated that the drug was safe and well tolerated. Dynogen plans to initiate a Phase 2 study of DDP733 in GERD patients in 2008. Previous clinical studies of the compound have demonstrated favorable safety and pharmacokinetic profiles. Dynogen licensed preclinical, clinical and manufacturing data and patent rights to DDP733 from Mitsubishi Pharma Corporation (now Mitsubishi Tanabe Pharma Corporation) in October 2004.

About Irritable Bowel Syndrome (IBS)

Irritable bowel syndrome is a chronic condition that is believed to be caused by the dysfunction of the muscles and/or nerves of the organs of the GI tract. Patients with IBS experience abdominal pain, discomfort and bloating accompanied by altered bowel habit that can include either diarrhea, constipation or both. IBS has prevalence of up to 12% of the general population, and females account for 80% of the patient population with severe cases. It is the most common disease diagnosed by gastroenterologists and one of the most common disorders seen by primary care physicians.

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. 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.

Dynogen Pharmaceuticals