Roche tries another way to solve the amyloid-beta conundrum


Against the odds Roche’s pivotal gantenerumab programme continues towards its inexorable conclusion some time in 2022. In the meantime the Swiss company today revealed another trick up its sleeve: the amyloid-beta MAb for Alzheimer’s disease, formulated in “brain shuttle” technology, has started a phase I study. The healthy volunteer trial was posted on earlier this year, and started dosing in the third quarter, but Roche has only now said that the compound involved, coded RO7126209 or RG6102, is brain shuttle gantenerumab. The brain shuttle technology was actually profiled almost two years ago in a paper in Cell that described preclinical studies suggesting that it could improve the delivery of antibodies to the brain without triggering immune responses against bystander cells. Roche describes it as a way of transporting large molecules across the blood-brain barrier, a strategy also being pursued by Denali, for instance. It is true that dose-limiting toxicities have hindered amyloid-beta MAbs, but after the failure of every single trial pursuing this approach it seems highly doubtful whether targeting amyloid-beta even without toxicity is the way forward in Alzheimer’s (Aducan’tumab, but that won't stop Biogen, April 24, 2019).

Active trials of gantenerumab
Study Detail Subjects tested Result
BP41192  Ph1: 5 RG6102 doses vs placebo 60 volunteers Ends Apr 2020
SCarlet RoAD Ph3: 2 gantenerumab doses vs placebo 799 prodromal pts Futile Q4 2014, study redesigned
Marguerite RoAD Ph3: gantenerumab vs placebo 389 mild pts Recruitment stopped Q4 2015
Graduate 1 Ph3: gantenerumab vs placebo 760 prodromal to mild pts Ends May 2022
Graduate 2 Ph3: gantenerumab vs placebo 760 prodromal to mild pts Ends May 2022
Source: Roche &

Share This Article