Myriad Genetics’ Flurizan (taren_urbil), the first in a new class of Alzheimer’s treatments, has almost halved the rates at which symptoms progressed in a Phase II study of patients with mild forms of the dementia.
In the two-year, Oxford University trial of 210 patients with mild disease, those on 800mg Flurizan twice daily saw their ability to perform day-to-day task decline 46% less that patients on placebo. The treatment also reduced the pace of decline in brain function by 36%.
Lead researcher Gordon Wilcock, based at Oxford’s John Radcliffe Hospital, said: “Treatment with 800 mg of taren_urbil twice daily had a signi_cant bene_t, which increased over time.” He added that the _ndings “justified Phase III studies of Flurizan at the 800 mg twice daily dose in patients with mild AD”.
Patients on lower doses, and those with moderate symptoms fared no better that patients on placebo, however, the Oxford team reports in Lancet Neurology. The results build on a 12-month, Phase II study already carried out by Myriad.
Flurizan (formerly known as R-_urbiprofen) is the first drug designed to inhibit the Gamma-secretase enzyme, which necessary for the production of amyloid-beta peptide in the brain. This toxic peptide is thought to initiate the tissue damage that leads to Alzheimer’s disease.
Dr Wilcock said the drug was generally well tolerated and that the most common adverse advents were diarrhoea, nausea, and dizziness, recorded at similar levels in the three treatment groups. Neurologist Dr Paul Aisen of the University of California, San Diego in the USA, said the positive effects of high-dose Flurizan were sufficient to justify the ongoing Phase-III trial of 1,800 patients, results from which are expected in the summer.
“With the need so enormous, and the potential effect of the bene_t suggested (although not proven) by these phase II results, the effort is indeed justi_ed despite the substantial uncertainty,” he said. He noted that several other promising anti-amyloid drugs were in the pipeline, as well. But Dr Aisen sounded a warning over this promising area of research.
He noted that Flurizan’s failure in the latest phase II study to help patients with moderate, as opposed to mild, symptoms indicated how hard it was to identify Alzheimer’s disease-modifying activity in relatively short phase-II trials. He said that because patients with mild to moderate AD, declined at a relatively slow and variable rates, “proof of efficacy, or even proof of mechanism, might be impossible in a Phase II study”.
