AstraZeneca Introduces Next Generation Prilosec

18 September 2000 00:00  [Source: ICB Americas]

By Lisa Jarvis

With patent expiry for AstraZeneca's Prilosec (omeprazole) looming, the company has developed a racemically pure version of the drug that it expects to launch next year. The upgraded version is an example of an industry-wide trend. Companies that are losing patent protection on blockbuster drugs are protecting their markets by introducing single-enantiomer versions of those drugs.

Antiulcerants were the leading class of therapeutic drugs in 1999, bringing in $15.6 billion in sales, according to IMS Health. Prilosec led the pack. Its global sales totaled $5.91 billion last year, making it the best-selling drug on the market.

Prilosec is slated to lose its US patent in April 2001, though if the Food and Drug Administration grants Prilosec pediatric exclusivity, its patent will extend to October 2001. Because Prilosec's worldwide sales represent roughly 40 percent of AstraZeneca's annual revenues, the company has developed a comprehensive plan to defend itself against generic competition.

"It has built up a tight fence around Prilosec through new formulations and indications, which protect specific aspects of Prilosec's production, formulation and use for 13 years beyond the basic patent expiry in 2001," Datamonitor notes.

AstraZeneca's primary line of defense is the development of a racemically pure version of the drug. The launch of Nexium (esomeprazole), the optical isomer of Prilosec (omeprazole), is a key component of the company's generic defense strategy. AstraZeneca filed for FDA approval last December, and the drug has already received EU approval.

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, giving it several advantages over Prilosec.

"We found that Nexium was metabolized differently than omeprazole. The way the enzymes see the molecule is different," says Dr. Doug Levine, chief medical officer of the gastrointestinal division at AstraZeneca. "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."

Nexium is expected to supplant Prilosec if AstraZeneca markets the new drug aggressively. A major indicator of its potential success is its performance in clinical trials.

"It's definitely viable," says Richard DiCicco, president of Falls Church, Va.-based Technology Catalysts International. He notes 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).

Nexium received the most significant vote of confidence upon receiving Swedish approval for a range of indications and two new treatment approaches. Nexium has already been launched in Sweden, and it will likely receive approval in other EU states.

Wall Street estimates that Nexium's global sales will total $145 million this year. Once the drug is launched in the US, which is expected by next January, according to Mr. DiCicco, and in the EU, its sales are expected to climb to $3.5 billion by 2003.

Industry observers note that Nexium is not a new type of drug. Prilosec and Nexium are both proton pump inhibitors. They reduce gastric acid secretion by inhibiting acid pump activity.

Analysts expect Nexium's success to hinge on AstraZeneca's marketing strategy. "The drug will probably fall or stand on its own merits. It's obviously going to be an important drug for Astra over the next couple of years until their new cholesterol-lowering drug comes on. A lot will depend on how they decide to launch Nexium," says Alex Zisson, an analyst at Chase, Humbrecht and Quist.

"The GI therapeutic area's strategy with Nexium is to certainly not rest on its laurels," says AstraZeneca's Dr. Levine. "We're optimistic we'll get approval for certain indications, but we also have a fairly ambitious supplemental NDA program where we're going to be looking at the safety and efficacy of the drug in a variety of other acid-related conditions."

The company stresses that the launch of Nexium is only part of an overall defense strategy, which includes a range of products in its pipeline that span many therapeutic areas. However, industry observers view Nexium as the company's most important defense in the near term.

The development of esomeprazole is an example of a trend in the life-cycle management strategy of many pharmaceutical manufacturers. By introducing a racemically pure version of a blockbuster drug, companies try to minimize or prevent revenue loss when the racemate's patent expires. The hope is that single enantiomer version will have significant benefits over the original, rendering generic versions of the original obsolete.

The global chiral technology market was worth an estimated $1.9 billion in 1999, of which chiral pharmaceutical products represented roughly $1.6 billion, according to the Norwalk, Conn.-based consultancy Business Communications Company. That figure is based on enabling products--chemicals that can be racemically separated or for which the chiral entity can be directly synthesized.

Analysts say it is still too early to judge whether the introduction of single enantiomers of major chiral drugs will enjoy widespread success. Levabuterol, a single-enantiomer version of Albuterol, an asthma medication marketed by Abbott and Sepracor, has been launched to little fanfare. "It's been relatively poorly received," Mr. Zisson says.

For some products, the single-isomer version may not be sufficiently better than the original version. Eli Lilly, in collaboration with Sepracor, is developing R-fluoxetine, an enantiomer of its best-selling anti-depressant Prozac (fluoxetine). Lilly lost its battle with Barr Laboratories over a generic version of Prozac and now faces patent expiry in 2001, two years earlier than expected.

Because it is unclear whether R-fluoxetine demonstrates any significant improvement over Prozac, many analysts do not expect the product to significantly offset Lilly's loss to an influx of generic versions of Prozac. As a result, the development of R-fluoxetine is part of a many-pronged generic defense strategy.

DAICEL CHEMICAL INDUSTRIES Ltd. is raising its prices for sorbic acid and potassium sorbate by 30c. per pound where contracts allow, effective October 1. The company plans to raise its prices by another 30c. per pound where contracts allow from January 1, 2001. The new prices are applicable not only in the US but also worldwide.

FLUOXETINE--Laboratorios Belmac SA and Laboratorios Danvur SL, wholly owned subsidiaries of Bentley Pharmaceuticals Inc., have received approval in Spain to market generic versions of fluoxetine, the generic equivalent of Eli Lilly's Prozac, in 20 mg capsules. The companies expect a fourth quarter 2000 launch.

NORETHINDRONE ACETATE--Pfizer has received Canadian approval for FemHRT (norethindrone acetate and ethinyl estraidiol) tablets, the first hormone replacement therapy (HRT) to combine estrogen and progesterone in a single, once-a-day pill. The drug treats meno-pausal symptoms and acts to prevent osteoporosis.

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