AC Immune partner Genentech to start second Phase 3 clinical trial for Alzheimer’s therapy crenezumab.
AC Immune SA, a Swiss-based, clinical stage biopharmaceutical company focused on neurodegenerative diseases, announced that its partner Genentech, member of Roche group, has decided to start a second Phase 3 clinical trial of the Alzheimer’s therapy crenezumab, an anti-Abeta antibody.
This new trial CREAD2 will recruit 750 patients with prodromal or mild Alzheimer’s disease. This new trial complements the current Phase 3 CREAD1 trial of 750 participants with prodromal or mild Alzheimer’s disease, expected to read out in 20201. Trial design details of CREAD2 are not yet available but will be posted on ClinicalTrials.Gov in due course.
Crenezumab was discovered by AC Immune using its SupraAntigen technology platform and out-licensed to Genentech in 2006 as a potential therapy for Alzheimer’s disease. AC Immune will not receive any milestone payments for the start of this second Phase 3 trial since the company already received a milestone payment when the CREAD1 trial started.
“We are delighted with the strong commitment of our partner Genentech to developing crenezumab as a potential disease modifying therapy for Alzheimer’s,” Prof. Andrea Pfeifer, CEO of AC Immune, commented. “Given the recent disappointing results of other therapies, all of us in the Alzheimer’s community need to redouble our efforts to combat one of society’s biggest challenges. We remain confident about the potential of crenezumab given it is distinct from other beta amyloid antibodies, predominantly blocking oligomers in the brain, and has a clinical development program that is using higher dosing and targeting earlier stages of Alzheimer’s disease.”
Important data to support the unique binding and increased dosing of crenezumab were presented by Genentech in December 2016 at the 9th Clinical Trials on Alzheimer’s disease Conference (CTAD) in San Diego.
Genentech has developed a comprehensive drug-disease progression model which predicts, relative to the Phase 2 trials, an increased potential of the CREAD Phase 3 clinical trial in patients with prodromal-to-mild Alzheimer by using the higher dose of 60mg/kg of crenezumab. The safety and pharmacokinetic data of the Phase 1b dose escalation study support the continued treatment of patients with crenezumab at a higher dose of 60mg/kg.
A paper was published in Scientific Reports on December 20, 2016, titled “Structure of crenezumab complex with Abeta shows loss of beta-hairpin.” Th publication describes the crystal structure of crenezumab targeting the beta amyloid oligomers. There is strong scientific evidence which suggests that those oligomers are the toxic form of Abeta and may be primarily responsible for neurotoxicity when compared to monomers and fibrils of the misfolded Abeta protein.
Crenezumab is shown to bind to a unique sequential, conformational epitope that only exists in the aggregated form of Abeta. This binding induces essential molecular interactions to break up and thereby solubilizes the oligomeric form of Abeta. The insights highlight crenezumab’s unique mechanism of action, particularly regarding Abeta oligomers, and provide a strong rationale for the evaluation of crenezumab as a potential AD therapy.
1 www.clinicaltrials.gov Identifier NCT02670083
Filed Under: Drug Discovery