Biotech Values

[DewDiligence]

AZN Reports Phase-2 Data for Oral Anticoagulant, AZD0837

[AZD0837 is an oral direct thrombin inhibitor that is similar to the failed drug, Exanta, but is less toxic based on the data to date. The drug has taken forever to advance to phase-3; it was originally delayed to work on formulation for qD doing and, more recently, it was delayed again—purportedly for deficiencies in the shelf-life. It is now slated to enter phase-3 in 2H09.]

http://www.reuters.com/article/marketsNews/idINLR38397120090329

›Mar 29, 2009
By Ben Hirschler

LONDON, March 29 (Reuters) - An experimental anticoagulant drug from AstraZeneca (AZN), which works in a similar way to its abandoned Exanta medicine, has shown promising results in a mid-stage Phase II study.

Researchers said on Sunday that AZD0837 appeared as effective as warfarin -- an old drug that is notoriously difficult to use -- and had a similar or lower bleeding risk.

Importantly, there were no signs of the liver toxicity problems that sank Exanta, said lead investigator Gregory Lip of City Hospital, Birmingham, England.

AstraZeneca intends to launch a large final Phase III study of AZD0837 in the second half of 2009.

The new drug, like Exanta, is a so-called oral direct thrombin inhibitor designed to prevent stroke in patients with atrial fibrillation (AF), a common heart arrhythmia.

Industry analysts believe a successful alternative to warfarin, which is sold by Bristol-Myers Squibb under the brand name Coumadin [LOL—warfarin has been available as a generic for several decades], could sell billions of dollars a year.

AstraZeneca had hoped Exanta would be the first but it was rejected by U.S. regulators in 2004 and two German companies, Bayer and Boehringer Ingelheim, have now developed rivals that are also being targeted at AF patients.

Warfarin's problems include food interactions and a need for constant patient monitoring.

Lip, who presented results for AZD0837 at the annual meeting of the American College of Cardiology in Orlando, Florida, said the various drugs would likely have different characteristics.

He believes AstraZeneca's medicine offers promise since it showed a comparable level of anticoagulation as warfarin, with a good safety profile.

In particular, the proportion of patients with liver enzyme levels more than three times the upper limit of normal during the Phase II study was similar with AZD0837 compared to warfarin, at 2.3 percent and 1.6 percent respectively.

"We have a drug that does not have the problems related to Exanta, in terms of liver function abnormalities," Lip said in a telephone interview.

"With Exanta we saw liver function problems in the region of 8, 10, 12 percent of the study population and we are not seeing anything like that here."

Total bleeding events were similar or less with all doses of AZD0837 tested, at between 5.3 and 14.1 percent, against 14.5 percent for warfarin, in the 955-patient study.

However, more patients on the new drug quit the study because of adverse events, mainly gastrointestinal, and they also experienced a mean 10 percent increase in creatinine levels, a possible sign of kidney problems, though Lip said this was "marginal" and went away when treatment ceased.

AstraZeneca had originally hoped to start Phase III tests of AZD0837, involving thousands of patients, before the second half of this year but the programme had to be delayed because of problems with the shelf life of the tablets. That issue is now being resolved, a spokesman said.‹