These disorders not only affect a patient' quality of life, but have been linked to an increased risk of some cancers. While the large patient population provides a vast opportunity for pharmaceuticals companies to be innovative, proton pump inhibitors (PPIS) such as AstraZeneca's Nexium (esomeprazole) have come to dominate the upper GI disorder market.
The landscape is set to change in the next 10 years as all of the blockbuster PPIs will experience patent expiry, however, according to a new report from independent market analyst Datamonitor, new market entrants will be required to demonstrate superiority over Nexium, which is currently the runaway market leader.
GERD is a very common upper GI disorder and most people will be familiar with the discomfort and pain that is associated with this disease – commonly known as heartburn – which arises when the contents of the stomach (i.e. bile and acid) are regurgitated up through the oesophagus towards the mouth. While the number of people with PUD has decreased in the last 20 years thanks to the identification of H. pylori as the major cause, the prevalence of GERD has grown significantly in this time. Datamonitor estimates that around 147 million people in the seven major markets, around 20% of the population, suffer from GERD.
Although there are many causes of reflux disease, one of the major risk factors for this disease is obesity, according to Datamonitor healthcare analyst Dr. James Wentworth.
“The main reasons behind the increasing GERD population in particular are lifestyle factors; the most important being body mass index and obesity. There is evidence to suggest that the obese are more than twice as likely as those with a normal weight to develop reflux symptoms and oesophageal erosions,” he says.
Given that the magnitude of the obesity problem is set to continue and has recently been branded as a risk comparable to climate change, there will be considerably more people suffering from reflux disease. At face value, most people would not consider reflux disease as a real problem, however: “It is important to stress that this disease can significantly affect quality of life, and if not properly controlled can lead to an increase risk of oesophageal carcinoma. Which incidentally, is one of the fastest growing forms of cancer in the world,” Dr Wentworth says.
There are a number of therapies that treat GERD, however, proton pump inhibitors, which prevent the production and release of stomach acid, have come to dominate the market. In 2006, the PPIs achieved massive sales of about US$16 billion. The market-leading branded PPI is AstraZeneca's Nexium (esomeprazole), which was developed as the follow-on compound to the company's original, first-to-market PPI, Losec (omeprazole), which came off patent in most of the major markets by 2002. Despite clinical trial data that showed only marginal superiority to Losec, Nexium has proved to be another success story for AstraZeneca and generated sales of over US$5 billion in 2006. AstraZeneca took a multi-pronged approach to Nexium's marketing Dr Wentworth says. “It conducted large-scale clinical trials for Nexium, it targeted the drug at thought-leaders, primary care physicians and spent millions on direct-to-consumer advertising.”
Indeed, in the US, which is the only major market to allow direct-to-consumer advertising, AstraZeneca built up a strong sense of brand awareness for Nexium by spending in excess of US$225 million on marketing their drug towards consumers, Dr. Wentworth says. “In a market where there is not much differentiation between the actual performance of PPI brands, most patients are, however, aware of the healing purple pill slogan for Nexium and that the drug treats heartburn. When seeing their physician, many patients will request Nexium by name.”
The presence of such a strongly marketed product such as Nexium provides a major barrier to entry for new products and subsequently, also to innovation in the market. Adding to this is the fact that the upper GI disorder market is set to become increasingly more genetically based in the next 10 years, owing to patent expiries of all the other blockbuster PPIs. “Generics are already a threat and will continue to be a threat”, Dr. Wentworth says. “The branded drug companies in the next few years are going to be looking at a smaller share of the market.”
Despite the crowded upper GI disorder market and generic threat, there is an unmet medical need for drugs that have a faster onset and longer duration of action as well as drugs for the PPI-unresponsive population. There is also a growing school of thought that new products will need to show clinical superiority over Nexium, Dr. Wentworth says. “The inclusion of Nexium as a comparator in head-to-head clinical trials is set to become essential to ensure market success and return on investment for pipeline products.”
The upper GI disorder pipeline falls into a wide variety of categories, however, research remains focused on developing PPIs. One such PPI that shows particular promise and is expected to meet these unmet needs is Negma's S-tenatoprazole-Na, which, at an early stage, shows signs of being better than Nexium. Provided that S-tenatoprazole-Na continues to show superiority against Nexium in future clinical trials, the more likely it is that it will compete very effectively with Nexium. Another PPI product that is expected to make a positive impact on the upper GI disorder market is TAP Pharmaceuticals' dexlansoprazole (TAK-390MR). In a move that mirrors the strategy that AstraZeneca used for Nexium, TAP Pharmaceuticals is expected to launch dexlansoprazole (TAK-390MR) as the follow-on to Prevacid (lansoprazole), Dr. Wentworth says. “The success of dexlansoprazole will be dependent on whether the drug can be launched before the patent protecting Prevacid expires in the major US market in 2009.”
