Genentech Provides Update on Phase III GRADUATE Program Evaluating Gantenerumab in Early Alzheimer’s Disease

– Phase III GRADUATE studies did not meet their primary endpoints of slowing clinical decline in people with early Alzheimer’s –

– The level of beta-amyloid removal by gantenerumab was lower than expected –

– Topline data will be presented at the Clinical Trials on Alzheimer’s Disease Conference –

– Genentech is committed to the Alzheimer’s community and will continue to develop novel diagnostics and potential treatments for Alzheimer’s –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced results from the Phase III GRADUATE I and II studies evaluating gantenerumab in people with mild cognitive impairment (MCI) due to Alzheimer’s and mild Alzheimer’s dementia, collectively called early Alzheimer’s disease. The studies did not meet their primary endpoints of slowing clinical decline. Gantenerumab was well tolerated including the subcutaneous administration.

“So many of our families have been directly affected by Alzheimer’s, so this news is very disappointing to deliver,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We are profoundly grateful to the study participants, their care partners and study sites for their contributions to this research. While the GRADUATE results are not what we hoped, we are proud to have delivered a high quality, clear and comprehensive Alzheimer’s dataset to the field, and we look forward to sharing our learnings with the community as we continue to search for new treatments for this complex disease.”

Study participants treated with gantenerumab showed a slowing of clinical decline in GRADUATE I and GRADUATE II of -0.31 (p=0.0954) and -0.19 (p=0.2998), respectively, from baseline score on the Clinical Dementia Rating-Sum of Boxes (CDR-SB); however, neither was statistically significant. This represents a relative reduction in clinical decline of 8% in GRADUATE I and 6% in GRADUATE II compared with placebo. The CDR-SB measures cognitive and functional change across six areas including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.

The level of beta-amyloid removal, the protein that builds up to make plaques in the brains of people with Alzheimer's, was lower than expected with gantenerumab treatment. Genentech will present topline findings from the GRADUATE I and II studies at the upcoming Clinical Trials on Alzheimer’s Disease (CTAD) Conference on Wednesday, November 30, 2022 at 4:15 p.m. PT.

Amyloid-related imaging abnormalities (ARIA) are a common radiological finding associated with amyloid-targeting therapies. The incidence of ARIA-E (edema or effusion) in the pooled gantenerumab arms was 25%, with the vast majority being asymptomatic and very few leading to treatment discontinuation. The incidence of isolated ARIA-H (haemosiderin) was balanced across the gantenerumab and placebo arms.

Genentech remains committed to Alzheimer’s, one of the most complex neurological disorders and a major public health challenge. The company is continuing to develop and deliver tests to enable early and accurate Alzheimer’s diagnosis and has a pipeline of investigational medicines for different targets, types and stages of the disease.

About the GRADUATE I and II studies

The Phase III GRADUATE I and II studies were two global, double-blind, randomized, placebo-controlled clinical trials evaluating the safety and efficacy of the investigational anti-amyloid monoclonal antibody gantenerumab in people with mild cognitive impairment (MCI) due to Alzheimer’s and mild Alzheimer’s dementia over 27 months. 1,965 study participants across 30 countries were randomized 1:1 to receive gantenerumab or placebo by subcutaneous injection titrated to reach a target dose of 510 mg administered every two weeks. The primary endpoint was the change from baseline score on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 116 weeks. The CDR-SB measures cognitive and functional change across six areas including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. There were 17 secondary endpoints including change in disease severity assessed using various neuropsychological and functional assessment tools (e.g., MMSE, ADAS-Cog, etc.), assessment of therapeutic levels of gantenerumab, incidence of adverse events, disease biomarkers and scans. A full list is available at www.clinicaltrials.gov.

About gantenerumab

Gantenerumab is a fully-human monoclonal IgG1 antibody, an investigational medicine that is subcutaneously administered and designed to target and bind to aggregated forms of beta-amyloid including oligomers, fibrils and plaques, and activate immune cells in the brain (microglia) to clear amyloid plaques and prevent further accumulation. Gantenerumab was discovered in collaboration with MorphoSys.

About Genentech in Alzheimer’s disease

With more than two decades of scientific research in Alzheimer’s, Genentech and Roche are working towards a day when we can detect the disease early and stop its progression to preserve what makes people who they are. Today, the companies’ Alzheimer’s portfolio spans investigational medicines for different targets, types and stages of the disease. It also includes diagnostic tools including digital, blood-based tests and cerebrospinal fluid (CSF) tests, aiming to more effectively detect, diagnose and monitor the disease. Yet the challenges of Alzheimer’s go well beyond the capabilities of science, and making a meaningful impact requires collaboration both within the Alzheimer’s community and outside of healthcare. Genentech and Roche will continue to work together with numerous partners with the hope of transforming millions of lives.

About Genentech in neuroscience

Neuroscience is a major focus of research and development at Genentech and Roche. Our goal is to pursue ground-breaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases.

Genentech and Roche are investigating more than a dozen medicines for neurological disorders including multiple sclerosis, stroke, Alzheimer’s disease, Parkinson’s disease and autism spectrum disorder. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.