Astra Zeneca held its first research and development presentation to city analysts as a merged company in London on December 6. The company outlined some of its drugs in development, including esomeprazole, a proton pump inhibitor due to be launched next year, which the company hopes will counteract the loss of sales following the patent expiry on omeprazole
Dr Claes Wilhelmsson (director, research and development) said that Astra Zeneca had a number of new products in late development and had 159 projects, including 57 new compounds, in the pipeline. The company aimed to deliver three "medically important, commercially attractive" products per year. Another aim was to deliver more than 15 candidate drugs into development per year by 2003 and to cut the time from candidate drug to launch to six years.
Dr Tom McKillop (chief executive) said that the pharmaceutical market was dominated by "mega brands" of which Astra Zeneca had two - Losec and Zestril. He predicted that five of its new products had the potential to become mega brands - esomeprazole, a "superstatin", an oral thrombin inhibitor, Viozan and Iressa.
The company announced at the meeting the submission of a new drug application to the US Food and Drug Administration for its proton pump inhibitor (PPI) esomeprazole. Esomeprazole (Nexium) was expected to be launched in Europe during the second half of next year, it said.
Dr Martin Nicklasson (head of the gastrointestinal [GI] franchise) said that esomeprazole had clinical benefits over omeprazole (Losec), Astra Zeneca's current PPI, on which the patent expires shortly. Esomeprazole was an optical isomer of omeprazole.
Dr Hans Glise (head of the GI therapeutic area) said that esomeprazole was a single isomer, giving it optimal pharmacokinetic properties. All other PPIs currently available were racemic mixtures. Individual patients responded differently to different isomers, making it difficult to predict how the drug would work.
Comparisons between omeprazole and esomeprazole have been made at the recommended dose for each drug: 20mg for omeprazole and 40mg for esomeprazole.
Dr Nicklasson presented data from trials comparing esomeprazole and omeprazole. In a study of 2,000 patients with reflux oesophagitis, treatment with esomeprazole resulted in a more than 10 per cent higher healing rate than with omeprazole. In addition, treatment with esomeprazole healed the same number of patients after four weeks as omeprazole therapy did after eight weeks.
Treatment for heartburn with esomeprazole resulted in freedom from symptoms after five days as opposed to nine days for omeprazole.
The new drug application had asked for use of esomeprazole in six indications: treatment and prevention of relapse of reflux oesophagitis, treatment of heartburn and gastro-oesophogeal reflux disease (GORD), long term management of GORD as "on demand" treatment and healing and eradication of Helicobacter pylori.
Esomeprazole was the first PPI for which a licence for "on demand" treatment had been applied. Dr Nicklasson said that 90 per cent of patients studied had maintained symptom control using 20mg esomeprazole on a "when required" basis.
Following the UK launch of omeprazole Losec MUPS tablets earlier this year, the original capsule form of the product was withdrawn. The capsules were then returned to the market. The reason given by Astra Zeneca for the re-introduction was that there had been problems with prescription endorsement(PJ 1999;263:778). Dr John Patterson (executive vice president, product strategy and licensing) said that eventually the plan was to market only the MUPS formulation, although he was not sure of the time scale for this.
A product for chronic obstructive pulmonary disorder, Viozan, is in phase III trials. It has a combined mechanism of action, being an agonist for both dopamine-2 receptors and b2 adrenoceptors. Dr Colin Reddrop (head of the respiratory therapy area) said that stimulation of dopamine receptors in the lung reduced mucus production, cough and breathlessness. Combining this with the increase in bronchodilatation from b2 stimulation gave significant improvements in total symptom scores for patients, he said. A new drug application was expected to be made for Viozan towards the end of 2001.
Phase III trials are also currently under way for Astra Zeneca's new statin, ZD4522. Dr Hamish Cameron (head of the cardiovascular therapeutic area) said that the drug was more effective than atorvastatin at lowering levels of LDL and increasing levels of HDL. A new drug application was expected to be made during the second quarter of 2001.
Another development within the cardiovascular area was an oral thrombin inhibitor, H376/95, which was in phase III trial for prevention of deep venous thromboembolism after orthopaedic surgery. The drug was an oral compound that converted to the active compound, melagatran, after absorption. Its predictable kinetics meant that regular anticoagulant monitoring (such as that required for warfarin) would not be needed, said Dr Cameron. Melagatran could also be given parenterally and a new drug application was expected to be filed for both H376/95 and melagatran in 2001.
Dr Brent Vose (director of the oncology therapeutic area) said that oncology provided another area for drug development. Aside from hormonal treatments and cytotoxics, Astra Zeneca was investigating novel biological approaches towards cancer treatment.
Iressa, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, had been shown to inhibit tumour growth in animals. EGFRs transmitted tumour growth signals and were present in many tumours. The presence of a large number of these receptors indicated a poor prognosis. Iressa was in phase II trials. It was being investigated both as monotherapy and in combination with other treatments for solid tumours including lung, gastric, colorectal and prostate cancers. A new drug application would be filed at the end of 2001.