AstraZeneca’s Nexium, Prilosec Fall Under Safety Review Spotlight in U.S., Canada

FDA Issues Preliminary Message

U.S. and Canadian regulators are undertaking a safety review of AstraZeneca’s Nexium (esomeprazole) and Prilosec (omeprazole), after studies raised concerns of a possible link with long-term use to cardiovascular risk. Both are used to treat acid reflux and ulcers, and belong to the proton pump inhibitors (PPIs) class of drugs. Prilosec is also sold over-the-counter (OTC) by U.S. firm Procter & Gamble for frequent heartburn.

The FDA said that analysis of an ongoing Nexium study and one Prilosec study had generated worries that long-term use might heighten the risk of heart attacks, heart failure and heart-related sudden death in comparison to surgery.

However, the FDA and Health Canada said doctors should not change prescribing patterns because their preliminary review did not show a higher risk of heart attack. The U.S. regulator also revealed it had not finished evaluating these studies and other data, adding that the safety review should be completed within three months.

The preliminary conclusion issued by the FDA is that the “observed difference in risk of heart attacks and other related heart problems seen in early analyses of two small long-term studies is not a true effect”. In line with its U.S. counterpart, Health Canada also stated that its preliminary probe had not found evidence to confirm a cardiovascular risk.

AstraZeneca released a statement saying it agreed with the FDA’s preliminary assessment. The British firm said it believes that the study results “conclude the products are not associated with an increased risk of cardiac events”.

The Two Studies in Question

At the end of May, the FDA received a preliminary analysis from AstraZeneca of two small studies of patients with severe gastroesophageal reflux disease (GERD). The studies were aimed at comparing the effects of the two drugs to surgery. The Nexium study analysed patients over the course of five years, while the Prilosec study lasted 14 years. AstraZeneca’s first analysis measured more patients on the drugs who had heart attacks, heart failure or heart-related sudden death.

However, the U.S. agency said that both studies may be somewhat distorted because the surgical patients tended to be younger and healthier than those administered the drug, therefore suggesting the heart link was a coincidence. Additionally, 14 other studies of patients treated for up to two years failed to find heart problems with Prilosec, the regulator said.

Outlook and Implications

In yet another cautious move, the FDA’s preliminary message falls in line with a new strategy to be more informative about potential public health risks.

The message is the earliest public warning that it has ever made during a safety review, as the regulator has moved quickly to prevent a repeat of the Avandia scenario. It was blasted for failing to alert the public for more than a year of studies suggesting the diabetes drug, made by U.K. firm GlaxoSmithKline (GSK), may increase the risk of heart attacks.

Despite the preliminary review clearing the drugs, the issue could inhibit sales as it is likely to create a shadow of doubt about their safety. Nexium is AstraZeneca’s top-selling drug, notching-up sales of US$5.2 billion last year. AstraZeneca clearly wants to avoid the GSK experience, where sales of Avandia suffered from panic over side effects.