AstraZeneca response to FDA and Health Canada communication regarding omeprazole and Nexium (esomeprazole)

AstraZeneca response to FDA and Health Canada communication regarding omeprazole
and Nexium (esomeprazole)

The FDA and Health Canada today issued public notifications on numerical
differences in cardiac event rates reported from two small, non-blinded,
long-term, clinical studies in patients with gastro-esophageal reflux disease
(GERD), comparing anti-reflux surgery with either omeprazole* or Nexium
treatment. The notifications were in response to a communication sent to all
Health Authorities by AstraZeneca in May 2007.

AstraZeneca agrees with the FDA in their preliminary assessment that “these data
do not suggest an increased risk of heart problems for patients treated with
omeprazole or esomeprazole” and that the observed differences in reported
cardiac event rates in the two studies is not a true effect. It is the view of
AstraZeneca that the study results conclude that the products are not associated
with an increased risk of cardiac events and do not change the overall
benefit/risk profile of omeprazole and Nexium. Therefore, patients should not
change their medication in the light of the study data. Pending their detailed
analysis of the two studies, the FDA and Health Canada confirm that prescribing
practices for omeprazole and Nexium  should not change. AstraZeneca fully
supports efforts by FDA and Health Canada to ensure transparency of emerging
safety information as it relates to marketed products.

Since the initial notification, AstraZeneca has forwarded to all Health
Authorities near complete data from these two trials, as well as reviewed
additional randomised controlled trial data from over 50,000 patients which
collectively show that omeprazole and Nexium are not associated with an
increased risk of cardiac events. 

The review of the data from the two studies demonstrate:

•  that there are no differences in the cardiac event reporting rates between
the treatment arms in the ongoing Nexium study (LOTUS).  

•  that whilst the older, non-blinded omeprazole study (SOPRAN) shows an
apparent difference in cardiac event reporting rates emerging during the first
prior to 12 months of dosing, a separate evaluation of other controlled clinical
trials of 12-24 months duration, involving omeprazole and placebo in
approximately 2,900 patients, shows a lower cardiac event reporting rate amongst
omeprazole treated patients than for placebo treated patients. 

This conclusion has been further validated by an analysis of post-marketing
safety data using the FDA and World Health Organisation spontaneous adverse
event report safety databases. Both databases suggest no indication of an
increased cardiac risk with any of the marketed PPI's, including omeprazole or
Nexium. 
AstraZeneca has made all omeprazole long-term clinical trial results, including
data from the above mentioned SOPRAN trial, as well as completed Nexium trial
results available on www.astrazenecaclinicaltrials.com/article/521037.aspx. Data
from the above mentioned Nexium (LOTUS) trial, which is ongoing, will be
available online once the trial has been completed.

Commenting on the data from the two studies, one of the world's leading experts
in gastroenterology,  Professor John Dent, Director, Nerve-Gut Research
Laboratory, Department of Gastroenterology & Hepatology, Royal Adelaide
Hospital, Australia, says: “It is not appropriate to draw any conclusions on
cardiovascular safety from the LOTUS and SOPRAN studies as they were only
designed to test major GERD treatment outcomes. Much evidence already exists
from data gathered appropriately from very large numbers of patients for the
purposes of risk assessment of omeprazole and esomeprazole therapy. These data
show no evidence of these therapies being associated with increased risk for
cardiovascular events. They extinguish any concerns raised by the SOPRAN and
LOTUS data in the light of the lack of validity of the SOPRAN and LOTUS data
from the perspective of cardiovascular risk assessment.”

Patients who have questions related to this communication should discuss their
treatment with their prescribing physicians. AstraZeneca will continue to work
with the FDA and Health Canada in their ongoing review of additional data. Other
Health Authorities who have reviewed the data have not indicated a need to
change prescribing information on these PPI's based on this information.

Losec (launched in 1988) and Nexium (launched in 2000) have been shown to be
beneficial for patients with acid related diseases such as GERD and NSAID
associated ulcers. Proton pump inhibitors (PPI's) are generally well tolerated
and Losec and Nexium have been used in the management of patients with acid
related diseases in over 1 billion patient treatments.  


- ENDS -
August 9, 2007

* Omeprazole is widely available as generic and OTC medication. AstraZeneca
trade names for omeprazole include Losec, Prilosec, Antra, Mopral

För mer information:
Staffan Ternby, informationsdirektör, AstraZeneca, tel 070-557 43 00
Staffan.ternby@astrazeneca.com
Pressansvarig Nexium AstraZeneca Sverige: Karolina Fränne, tel 0733-351 427
karolina.franne@astrazeneca.com