Additional Phase II Data Demonstrate Improvement In Reported Symptoms In Patients Who Still Experience GERD Symptoms Despite PPI Therapy

Main Category: Acid Reflux / GERD
Also Included In: GastroIntestinal / Gastroenterology
Article Date: 05 Jun 2009 - 5:00 PDT

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Adding AZD3355, a novel GABAB receptor agonist, to a proton pump inhibitor (PPI) in patients with Gastroesophageal Reflux Disease (GERD), resulted in a 35% reduction in the mean total number of reflux episodes 0-24 hours after dose, compared with placebo.[i] These data were presented at the Digestive Diseases Week annual meeting (DDW®, 30 May - 4 June, Chicago).

Additional data from a proof of concept study also reported that add-on treatment with AZD3355 to a PPI resulted in a higher proportion of reported symptom free days for heartburn (36 percent vs 21%) and regurgitation (37percent vs 23 percent) in patients with persistent symptoms despite daily proton pump inhibitor (PPI) therapy.[ii]

The most common adverse events occurring with an incidence ≥6 percent in any group were diarrhea, paraesthesia, nausea and fatigue. ii

GERD develops as a result of stomach contents refluxing into the esophagus causing troublesome symptoms and/or complications.[iii],[iv] The recommended treatment for GERD is PPI therapy. However, clinical studies have found that 20-30% of the patients still have persistent symptoms while taking a PPI.[v] Reflux symptoms occur mainly when the Lower Esophageal Sphincter (LES) (located between the stomach and the esophagus) relaxes in the absence of swallowing, known as Transient Lower Esophageal Sphincter Relaxations (TLESRs), and causes reflux of stomach contents.[vi],[vii],[viii],[ix] As a GABAB receptor agonist, AZD3355 targets the LES to decrease reflux episodes. x, xi, xii

Guy Boeckxstaens, Professor of Gastroenterology, University Hospital Leuven, Belgium said: "PPIs are the cornerstone of therapy for GERD patients, however there are many patients who still experience persistent, recurring symptoms, despite PPI treatment. Research and innovation to address the pathophysiology of reflux are important in order to find other treatment options besides PPIs to address the unmet need in this patient group."

Data from a study on healthy volunteers presented today showed that AZD3355 reduced the mean number on TLESRs by 36% compared to placebo.xiii In addition, AZD3355 significantly increased LES pressure, reduced esophageal acid exposure and proximal reflux events when used as add-on treatment to a PPI in patients with GERD with symptoms despite PPI therapy.i

The findings provide proof of concept of AZD3355 and a direction for further development of the drug.ii

About Digestive Diseases Week

DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 30 - June 4, 2009, at the McCormick Place, Chicago, IL. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. For more information, visit http://www.ddw.org.

  References

[i] Boeckxstaens, G. Effect of AZD3355, a Novel GABAB Agonist, on Reflux and Lower Esophageal Sphincter Function in Patients With GERD With Symptoms Despite Proton Pump Inhibitor Treatment. Data to be presented at Digestive Diseases Week 2009 - Poster M1861

[ii] Boeckxstaens, G. Efficacy and Tolerability of the Novel Reflux Inhibitor, AZD3355, as Add-on Treatment in GERD Patients with Symptoms Despite Proton Pump Inhibitor Therapy. Data to be presented at Digestive Diseases Week 2009 - Poster M1875

[iii] Vakil N, Van Zanten SV, Kahrilas P, Dent J, Jones R and the Global Consensus Group. The Montreal Definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006;101:1900-20.

[iv] Malfertheiner P, Hallerbäck B. Clinical manifestations and complications of gastroesophageal reflux disease (GERD). Int J Clin Pract 2005; 59:346��"55.

[v] Fass R, Drugs 2007; 67: 1521-30

[vi] Kahrlias PJ, Shi G. Pathophysiology of gastroesophageal reflux disease: the antireflux barrier and luminal clearance mechanisms. In Orlando RC. ed Gastroesophageal reflux disease. New York: Marcel Dekker. 2000. 137-64.

[vii] Mittal RK, Balaban DH. The esophagogastric junction. N Engl J Med. 1997.336: 924-32.

[viii] Dodds WJ, Dent J, Hogan WJ, et al. Mechanisms of gastroesophageal reflux in patients with reflux esophagitis. N Engl J Med. 1982. 307: 1547-52.

[ix] Dent J, Dods WJ, Friedman RH, et al. Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects. J Clin Invest. 1980. 65: 256-67. F

[x] Ciccaglione AF, Marzio L. Effect of acute and chronic administrations of the GABAB agonist baclofen on 24 hours pH metry and symptoms in control subjects and in patients with gastro-oesophageal reflux disease. Gut 2003;52:464-470.

[xi] Boeckxstaens GE, Tytget GNJ: More pathophysiologically oriented treatment of GORD? Lancet 2002, 359:1267-1268.

[xii] Hirsch DP, Tytgat GNJ, Boeckzstaens GEE: Transient lower esophageal sphincter relaxations: a pharmacological target for gastroesophageal reflux disease [review]. Aliment Pharmacol Ther 2002, 16:17-26.

[xiii] Boeckxstaens, G, Rydholm, H, Adler J, Ruth, M. Effect of AZD3355, a Novel GABAb Receptor Agonist, on Transient Lower Esophageal Sphincter Relaxations in Healthy Subjects. Data to be presented at Digestive Diseases Week 2009 - oral presentation 772

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