AD trials Flashcards
Aducanumab (Biogen)
Completed phase Ib trial - the PRIME study - 165 AB positive pts with mild AD received 1 year of monthly injections of aducanumab or placebo. Amyloid PET imagine demonstarted a clearance of AB in a dose-dependent and time-dependent manner and stabilisation of cognitive decline as measured by MMSE.
20% of pts developed amyloid related imaging abnormalities
now Two phase III trials were discontinued for futility in 2019 (interim anayliss showed they would miss thier primary endpoints. However, in October 2019 Biogen announced that the interim analysis was wrong and there was a favorable reanalysis of of data from one of the studies (EMERGE) suggesting imporvement in clinical measures (MMSE anf so on) and amyloid brain load reduction (AB PET). On November 6 2020 FDA voted against approval - citing weaknesses in efficacy data and recommended a confirmatory trial.
verubecestat
In Feb 2017 Merck halted its phase 2 after it was reported to have ‘virtually no chance’ of working according to an independent panel of experts
semagacestat
Showed promise in preclinical animal studies. And was the first of its kind in phase III trials. Lilly started two Phase 3 tirals (IDENTITY-1 and IDENTITY-2 with 3000 pts total). Both trials were to run until 2012, but were halted in 2011 because both increased risk of skin cancer and infections and showed lack of efficacy. Notably, both cognition and function only did not improve but worsened in all treatment groups. Has been terminated.
ACI-35 - synthetic tau fragment thought to elicit immune response against physiological forms of the protien
Results of a phase 1b trial were announced in 2020 - raised no safety concerns but elicited a weak immune response and booster shots had little effect. A redesigned version ACI-35.030 includes a second adjuvent to activate Th cells. This produced a stronger immune response in rhesus monkeys in preclinical trials. ACImmune (company) announced in Feb 2021 in a press release that participants had developed antibodies against phos-Tau, with high IgG titres - showed no data to support these claims. Recently has also stated positive interim data stated in further conferences - Feb 2022. Completion aimed in 2023.
