AstraZeneca withdraws Exanta
AstraZeneca (AZ) has withdrawn Exanta (melagatran/ximelagatran) from the market and terminated its development following new patient safety data which indicates a potential risk of severe liver injury.
AstraZeneca (AZ) has withdrawn Exanta (melagatran/ximelagatran) from the market and terminated its development following new patient safety data which indicates a potential risk of severe liver injury.
The anticoagulant is used for the short-term prevention of venous thromboembolism (VTE) following orthopaedic surgery (OS). The company estimates that approximately 400 patients are currently being prescribed the drug and is asking them all to terminate their usage without consulting their doctor.
The data was gathered in the EXTEND trial, which was examining the use of Exanta for up to 35 days post-operatively. The drug had only gained marketing approval for 11-day use and a rapid onset of the signs and symptoms of severe liver injury was seen in the weeks following the end of the 35-day treatment.
Liver findings had previously been observed during clinical trials of chronic use, as referred to in Exanta's prescribing information, although this specific observation had not previously been made. AZ says that the finding 'indicates that regular liver function monitoring may not mitigate the possible risk', and that while no evidence of a risk of liver injury with 11-day use exists it has concerns over any unapproved use beyond 11 days.
Two ongoing Exanta clinical trials are to be discontinued and Exanta-treated patients will be switched to other treatments. The development of AZD0837, which has the same mode of action as Exanta but is chemically different, will continue as planned. Currently in Phase II, it has treated 167 patients for three-months with no liver signal.
AZ has informed the regulatory authorities of its decision and is communicating with all prescribers and healthcare professionals to advise them that no new patients should be started on Exanta.
David Brennan, ceo, AZ, commented: 'We have decided to take this precautionary action in the interests of patient safety. There are a number of alternative options for short-term post-operative anticoagulation following orthopaedic surgery. We would like to recognise the involvement of doctors, patients and scientists and their commitment to the development of Exanta over the past years.'
Total sales of Exanta in 2005 amounted to $575,000. The drug is known as Exarta in Italy and Sweden.