Biopharmaceuticals Gastroenterology Regulatory

 News Release - May 12, 2009

AstraZeneca Secures Approval for Nexium (esomeprazole) In Peptic Ulcer Bleeding

First PPI licensed for prevention of peptic ulcer re-bleeding - a condition associated with significant morbidity and mortality

LONDON--(HSMN NewsFeed)--AstraZeneca announced today that it has completed the Mutual Recognition Procedure in Europe with Sweden as Reference Member State for the use of Nexium® (esomeprazole) to prevent peptic ulcer re-bleeding in adults.1

Esomeprazole i.v. is the first proton pump inhibitor (PPI) to be indicated in Europe for prevention of re-bleeding following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers. The i.v. treatment should be followed by oral acid suppression therapy. Esomeprazole oral also received the indication for prolonged treatment after i.v. induced prevention of re-bleeding peptic ulcers. National approvals will follow throughout 2009.

“Peptic ulcer bleed (PUB) is a common and potentially life-threatening complication of peptic ulcer disease and until now there has not been an approved pharmacological treatment to reduce the risk of re-bleeding after endoscopic treatment, the current standard treatment for bleeding peptic ulcers with high risk for re-bleeding. Currently, approximately 20% of patients with PUB may experience a re-bleed even after endoscopic treatment2,3 and patients experiencing re-bleeding after initial treatment of PUB have a more than three-fold risk of death.3 The approval of Nexium® for preventing peptic ulcer re-bleeding in adults fills a significant gap in current treatment options available to physicians to manage PUB after endoscopic treatment,” said Professor Ernst Kuipers of The Erasmus Medical Centre, Rotterdam.

The licence application was based on the findings from a large, multinational, randomised, double-blind, placebo-controlled study that was conducted in 16 countries across Europe, Asia and Africa.4 The study population consisted of 767 patients, male and female, aged 18 years or over, who had undergone successful endoscopic haemostatic treatment for PUB. The patients received high doses of i.v. therapy of esomeprazole (80mg intravenous bolus infusion for 30 minutes followed by esomeprazole 8mg per hour i.v. for 71.5 hours) or matching placebo infusion for 72 hours.4 All patients then additionally received once-daily oral esomeprazole 40mg for 27 days.4

Overall, the study showed that esomeprazole significantly reduced the number of patients having a re-bleed after initial endoscopic haemostatic treatment of PUB by almost half. The treatment was found to be more effective within 3, 7, and 30 days in reducing re-bleeding4 and reduced the use of hospital resource compared with placebo.5 Esomeprazole was also considered to be generally well tolerated.6

Until now, no other PPI has demonstrated an overall benefit in high risk peptic ulcer bleeding patients in published international, multi-center studies of PUB in predominantly Caucasian patient populations. 7-12

Esomeprazole is already approved in Europe for the treatment of gastroesophageal reflux disease (GORD), for the treatment of reflux esophagitis (RO) and for the long-term management of patients with healed esophagitis to prevent relapse. Esomeprazole is also indicated in the Europe for healing of gastric ulcers associated with NSAID therapy and prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk.1 Esomeprazole in combination with an appropriate antibacterial therapeutic regimen is also approved for the eradication of H. pylori and the healing of H. pylori associated duodenal ulcer and the prevention of relapse of peptic ulcers in patients with H. pylori associated ulcers. Esomeprazole i.v. 40 mg powder for injection/infusion as a solution is approved in Europe for gastric antisecretory treatment when the oral route is not possible.

AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of prescription medicines and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US$ 31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. For more information about AstraZeneca, please visit: www.astrazeneca.com

Notes to editors

PUB

• A peptic ulcer is a deep and sharply demarcated break in the lining of the stomach or duodenum – when in the stomach it is described as a gastric ulcer and when in the duodenum a duodenal ulcer 13,14
• Peptic Ulcer Bleeding (PUB) is a potentially life-threatening event that occurs as a complication of peptic ulcer disease. PUB occurs when the ulcer erodes into an underlying blood vessel
• In Europe, PUB affects approximately 50 people per 100,000 population per year 3,15
• The condition is most common in the elderly, with two-thirds of patients over the age of 60 years and 27% over 80 years 16
• Those at particular risk of PUB include patients aged more than 60 years17 with:
• Co-morbidity (arthritis, cardio- vascular diseases) - many patients with PUB also have underlying diseases, such as diabetes, cancer, or have recently undergone surgery18
• A high level of polypharmacy, including NSAIDs and low-dose ASA patients19,20
• Those infected with H. pylori19

References

1. Nexium Prescribing Information, AstraZeneca

2. Holtman G, Howden W. Review article: management of peptic ulcer bleeding – the roles of proton pump inhibitors and H.pylori eradication. Ailmentary Pharmacology & Therapeutics 2004; 19 (Suppl 1): 66-70.

3. Van Leerdam M, Vreeburg E, Rauws E at al. Acute upper GI bleeding: Did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/4 and 2000. American Journal of Gastroenterology, 2003; 98(7):1494-9.

4. Sung et al. Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding Annals of Internal Medicine 2009;150 (7): 455-464

5. Barkun A et al. High-dose intravenous esomeprazole in peptic ulcer bleeding: new clinical data applied to a european cost-effectiveness analysis Gut 2008;57(Suppl II):A99: Abs OP458

6. Kuipers. High dose intravenous esomeprazole is safe and well tolerated in patietns with peptic ulcer bleeding Gut 2008;57(Suppl 2): A352: P1237

7. Sung J, Mössner J, Barkun A, et al. on behalf of the PUB Study Group. Intravenous esomeprazole for re-bleeding: rationale / design of the Peptic Ulcer Bleed Study, Alimentary Pharmacology & Therapeutics 2008; 27, 666–677

8. Van Rensburg C, Racz I, Bailey R et al. Prevention of peptic ulcer rebleeding using continuous infusion of pantoprazole versus rantidine: A multicenter multinational, randomized, double-blind parallel group comparison. Canadian Journal of Gastroenterology 2004 (e-supplement): Abs 149.

9. Jensen D, Pace S, Soffer E et al. 315 Study Group. Continuous infusion of pantoprazole versus ranitidine for prevention of ulcer rebleeding: A U.S. multicenter, randomized, double-blind study. American Journal of Gastroenterology 2006; 101:1991-

10. Hasselgren G, Lind T, Lundell L et al. Continuous infusion of omeprazole in elderly patients with peptic ulcer bleeding. Results of a placebo-controlled study. Scandinavian Journal of Gastroenterology 1997;32 (4):328-33.

11. Schaffalitzky de Muckadell O, Havelund T, Harding H et al. Effect of omeprazole on the outcome of endoscopically treated bleeding peptic ulcers. Randomized double-blind placebo-controlled multicentre study. Scandianvian Journal of Gastroenterology 1997;32 (4):320-7.

12. Lin H, Lo W, Lee F et al. A prospective randomized comparative trial showing that omeprazole to maintain high intragastric pH in patients with peptic ulcer after successful endoscopy. Arch Intern Med vol: 158 pp36-41, 1998.

13. Nexium.net. Retrieved March 2008.

14. Dorland’s Illustrated Medical Dictionary. Ed: Taylor EJ. WB Saunders Company Philadelphia, 1985.

15. Lassen A. Complicated and uncomplicated peptic ulcers in a Danish county 1993-2002: a population-based cohort study. Am J Gastroenterol 2006;101(5):945-53.

16. Sung J. Current Management of Peptic Ulcer Bleeding. Nat Clin Pract Gastroenterol Hepatol 2006; 3(1): 24-32

17. Laine L, Peterson W. Bleeding petic ulcers. N Eng J Med 1994: 331

18. Ruigomez A, Garcia Rodriguez LA, Hasselgren G, Johansson S, Wallander MA.. Overall mortality among patients surviving an episode of peptic ulcer bleeding Journal Of Epidemiology & Community Health 2000;54(2): 130-133

19. Lanas A, Scheiman J. Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment. Current Medical Research and Opinion 2007;23(1):163-73.

20. Scheiman J, Yeomans N, Talley N et al. Summing the risk of NSAID therapy. The Lancet 2007; 369:1580-1581.

Source: AstraZeneca

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