SpicyIP Tidbits: It’s a Case of Purple Heartburn

Here’s the story so far. AstraZeneca, the Anglo-Swedish manufacturer of prescription drugs had a basic patent on Prilosec (Omeprazole), a drug used to treat gastroesophageal reflux disease (acid reflux) and heartburn. Gastroesophageal reflux disease is the name given to erosions in the oesophagus on account of churning of pepsin in the stomach over a period of time which chips away at the delicate lining of oesophagus. This patent was supposed to expire in April 2001. However, the company came up with a new formulation in the form of Nexium (esomeprazole), also known as the Purple Pill, which protects specific aspects of Prilosec. Apparently,this was done because Prilosec earned the company $5.91 billion in the year 1999 alone.

Nexium too was granted a US patent (US 6369085) which according to the company is scheduled to expire in 2019. However, this patent has been challenged by several companies, notably Ranbaxy and Israel-based Teva Pharmaceutical in separate suits. In fact, Ranbaxy went ahead for a first-to-file status under the Hatch Waxman Act of 1984. This Act is designed to promote generic versions of patented drugs and gives Ranbaxy a 180-day window during which it shall have exclusive marketing rights to the drug on the expiry of the Nexium patent. Also, the USFDA has given a tentative approval to Ranbaxy’s generic version of Nexium. Following the challenge to the Nexium patent, an automatic stay of 30 months was ordered. This stay is lifted automatically at the end of the said period which will be on April 14, 2008 in the case of Ranbaxy and in July 2008 for Teva. It is being speculated that Ranbaxy and Teva Pharma may jointly go for an “at risk” launch.

“At risk” launch occurs when a generic company launches a product after the automatic 30-month stay granted at the beginning of patent litigation between two companies, but before the completion of the case and the expiration of the patent. The danger to the generic company is that if it loses the litigation, it is then liable for triple the damages it would normally incur for patent infringement. But if it wins, the generic company’s drug is on the market faster than a competitor’s. Past experience says that a loss in the Court isn’t sufficiently huge to deter the generic companies which can offset future losses with big gains from early sales. Teva in particular has been using this strategy to its advantage which has emboldened other generic manufacturers.

Rumour mills are working overtime saying that AstraZeneca would probably cut a deal with the challengers, but the company has denied the possibility of any such deal saying that it was confident of winning the case on the merits of the patent. Further, Astra has won seven out of eight patent disputes. However, several industry observers are divided on this issue. According to them, the trend is that companies which lose patent protection on blockbuster drugs protect their markets by introducing single-enantiomer versions of those drugs and most feel that Prilosec and Nexium fit this pattern. Prilosec is a racemic mix of enantiomers, which can be likened to the left-handed and right-handed versions of a molecule. With Nexium, the S-enantiomer has been isolated, which according to AstraZeneca gives it several advantages over the basic patent. Dr. Doug Levine, chief medical officer of the gastrointestinal division at AstraZeneca, opined in 2000 as follows:

“We found that Nexium was metabolized differently than omeprazole. The way the enzymes see the molecule is different. I like to use the analogy of a key in a lock. If you had a mirror image to that key, it wouldn’t necessarily fit into the key hole.”

Richard DiCicco, president of Falls Church Technology Catalysts International, too was confident that Nexium is clinically superior to omeprazole at four endpoints: fast healing of reflux esophagitis, fast symptom relief, new approach to long-term management of symptomatic GERD (gastro-esophageal reflux disease) and new approach to helicopylary (the treatment of ulcers caused by bacteria). A few others feel that not every such drug which is an isolated enantiomer receives the same amount of success for it depends on that particular case. For instance, Levabuterol, a single-enantiomer version of Albuterol, an asthma medication marketed by Abbott and Sepracor, came and went without a whimper. Accordingly, without resorting to comparisons, one will have to judge the merits of the drug individually and cannot blindly draw parallels on the basis of success or failure of other drugs.

The complete details are available here.