Genentech Presents Positive Data from Trials on Crenezumab and Gantenerumab for Alzheimer’s

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by Alice Melão |

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crenezumab and gantenerumab

The latest clinical data from Genentech on crenezumab and gantenerumab demonstrate the investigational therapies’ potential to reduce amyloid aggregates in Alzheimer’s disease patients.

Trial results were discussed in several presentations at the 2018 Alzheimer’s Association International Conference (AAIC), recently held in Chicago.

“The range of data that Roche and Genentech are presenting at AAIC is a testament to our commitment to bring new treatments to help the many millions of people living with Alzheimer’s disease,” Sandra Horning, MD, chief medical officer and head of global product development at Roche, said in a press release.

One of the hallmarks of Alzheimer’s disease is the formation of protein plaques and tangles between nerve cells. These are made of beta-amyloid fragments that stick together and accumulate between nerve cells, disrupting their function.


Crenezumab is an investigational monoclonal antibody first discovered by AC Immune and now being developed by Genentech, a Roche Group company. It was designed to target all forms of beta amyloid molecules, and has been evaluated for the treatment of prodromal to mild Alzheimer’s disease.

In the study, “Target Engagement in an AD Trial: Crenezumab Lowers Aβ Oligomer Levels in CSF,” researchers conducted a post-hoc analysis of data collected during the ABBY (NCT01343966) and BLAZE (NCT01397578) Phase 2 trials.

They included 104 Alzheimer’s patients from these randomized trials who were treated with under-the-skin (subcutaneous) injections of 300 mg crenezumab or placebo every two weeks, or injections directly into the vein (intraveneous) of 15 mg/kg crenezumab or placebo every four weeks, for a total of 68 weeks. Samples of cerebral spinal fluid were collected to determine changes in beta amyloid oligomer levels.

The data revealed that both crenezumab treatments, intraveneous and subcutaneous, could effectively lower beta amyloid levels in these patients.

Approximately 86% of intraveneous- and 89% of subcutaneous-treated patients had significantly lower levels of the damaging proteins by the end of the study, compared with initial values. They experienced a median reduction of 42% and 48%, with 21% and 13% of patients in each group falling below the lower limit of beta amyloid oligomer detection.

“These first of their kind data are very promising as they support the proposed mechanism of action of crenezumab to preferentially bind to and promote removal of neurotoxic oligomers, a form of Abeta,” Andrea Pfeifer, CEO of AC Immune, said in a press release announcing the trials’ results. “We are excited about the potential of crenezumab, as a disease-modifying therapy, given its distinct differentiation from other beta-amyloid antibodies in terms of target specificity and safety.”

Genentech is currently conducting two Phase 3 trials — CREAD 1 (NCT02670083) and CREAD 2 (NCT03114657) — and an extension study, CREAD OLE (NCT03491150), to further evaluate the long-term clinical benefit of this investigational therapy in early Alzheimer’s patients.


Similar to crenezumab, gantenerumab is also an engineered antibody designed to prevent the accumulation of beta amyloid proteins in brain cells.

The study “24-Month Amyloid PET Results of the Gantenerumab High-Dose Open Label Extension Studies,” revealed two-year data from open-label extension trials of gantenerumab. Results showed that treatment with high-dose gantenerumab could significantly reduce beta amyloid burden in patients with early Alzheimer’s disease at 12 and 24 months.

Updated data on ongoing open-label extension trials Scarlet RoAD (NCT01224106) and Marguerite RoAD (NCT02051608) showed that administration of 1,200 mg of gantenerumab per month resulted in up to three times more amyloid reduction in one year than that achieved with two years of low-dose treatment (225 mg).

Preliminary analysis in data collected from 40 patients after two years of treatment with 900 to 1,200 mg of gantenerumab revealed that 46.4% experienced a significant reduction in beta amyloid burden bellow positivity threshold, as determined by positron emission tomography (PET) scans.

Analysis of the safety profile in these open-label extension studies did not reveal any new or unexpected safety issues related to longer exposure to high-dose gantenerumab, besides amyloid-related imaging abnormalities (ARIA) and injection-site reactions (ISR), which were previously identified.

The incidence of ARIA affecting the brain blood vessels increased in frequency with a higher dose of the therapy. But most events were asymptomatic and non-serious, and all were manageable with close monitoring through monthly magnetic resonance imaging (MRI) scans.

These safety results were presented in two oral presentations, “Update on the Safety and Tolerability of Gantenerumab in the Ongoing Open-Label Extension (OLE) of the Marguerite Road Study in Patients with Mild Alzheimer’s Disease (AD) after Approximately Two Years of Study Duration” and “Update on the Safety and Tolerability of Gantenerumab in the Ongoing Open-Label Extension of the Scarlet Road Study in Patients with Prodromal Alzheimer’s Disease after Approximately 2 Years of Study Duration.

These latest safety results provide further support for the use of an optimized titration to achieve high-dose gantenerumab administration during the ongoing Phase 3 GRADUATE program.

This program includes the GRADUATE1 (NCT03444870) and GRADUATE2 (NCT03443973) trials, which are currently recruiting patients with early Alzheimer’s disease, ages 50 to 90, at clinical sites across the U.S., Europe, South America, Australia, and Asia.