Elan and Transition rejig Phase II Alzheimer's trials on safety data
This article was originally published in Scrip
Elan and Transition Therapeutics have stopped using the two highest doses of their Alzheimer's disease drug candidate ELND005 in two Phase II trials due to safety concerns.
"Greater rates of serious adverse events, including nine deaths, were observed among patients receiving the two highest doses. A direct relationship between ELND005 and these deaths has not been established," the companies said in a statement.
Whereas Elan's share price fell by only 2% on the NYSE on December 15th, Transition's share price fell by 44%, to $4.41 on Nasdaq.
"The [Independent Safety Monitoring Committee] and both companies concur that the tolerability and safety data are acceptable among patients receiving the 250mg dose and that the blinded study should continue for this dose and the placebo group," the companies said.
The 18-month Phase II trial "AD201" enrolled 350 patients with mild to moderate Alzheimer's disease who were randomised to 250mg, 1,000mg or 2,000mg of ELND005 twice daily or placebo. Those patients on the higher doses have now been withdrawn, but the trial is continuing unchanged for the other two arms of the trial.
The open-label 12-month extension study "AD251" will be modified to dose patients only at 250mg twice daily.
AD201 is due to finish in May 2010, and AD251 is due to finish in April 2011. Both are assessing tolerability and safety as a primary endpoint.
ELND005 is an orally available beta-amyloid precursor protein antagonist. Elan was previously developing the beta-amyloid targeting antibody bapineuzumab, together with Wyeth (now Pfizer), for Alzheimer's disease. It sold its rights to the drug to Johnson & Johnson earlier this year, however (scripnews.com, September 18th, 2009). In an ongoing Phase III trial of bapineuzumab, the top dose was also dropped due to concerns about vasogenic oedema (scripnews.com, April 3rd, 2009).