Roche Engages in FDA Discussions for Alzheimer’s Drug Candidate Gantenerumab

Compiled by | Tom Li

Currently, Roche is in discussions with the U.S. Food and Drug Administration (FDA) regarding its investigational Alzheimer's disease drug candidate, Gantenerumab. Roche CEO Severin Schwan recently stated in an interview that Roche will complete the Phase III trials for Gantenerumab in the second half of 2022.

According to a study published in *Nature Medicine* this June, gantenerumab improved the levels of multiple biomarkers in patients with hereditary Alzheimer’s disease. Among trial participants with dominantly inherited Alzheimer’s disease (DIAD), treatment with Roche’s gantenerumab reduced brain biomarkers of disease and neurodegeneration that drive early-onset memory loss and other symptoms in patients.

The DIAN-TU-001 (NCT01760005) trial compared the efficacy of gantenerumab, manufactured by Roche and its US subsidiary Genentech, with solanezumab from Eli Lilly in patients with rare, inherited, early-onset Alzheimer's disease. Compared with the control group, DIAD patients treated with gantenerumab exhibited a significant reduction in amyloid plaques, along with decreased levels of total tau and phosphorylated tau181 (p-tau181) in the cerebrospinal fluid (CSF). Although the trial was not designed to evaluate the cognitive effects of gantenerumab in patients who initiated treatment prior to symptom onset, the study did not demonstrate evidence of cognitive benefit for Alzheimer's disease patients.

Researchers indicated that patients enrolled in the trial were at multiple stages of the disease, including both asymptomatic and symptomatic phases. Overall, the safety profile of Gantenerumab in this trial was consistent with that observed in other clinical trials of the investigational drug, and no new safety concerns were identified. DIAN-TU researchers will also conduct an exploratory open-label extension study of Gantenerumab to continue monitoring the drug’s effects on patient symptoms over time. Additionally, two other Phase 3 trials of Gantenerumab (GRADUATE 1 and GRADUATE 2) are currently underway in patients with early sporadic Alzheimer’s disease.

Schwan revealed that Roche plans to complete the Phase III clinical trial for this drug in the second half of 2022.

Gantenerumab is a monoclonal antibody targeting the β-amyloid peptide. In February 2020, Roche announced that gantenerumab failed to meet its primary endpoint in patients with early-onset hereditary Alzheimer's disease, and the therapy did not significantly slow the rate of cognitive decline. In June 2020, Roche's gantenerumab injection received clinical trial approval from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) for the treatment of patients with prodromal to mild Alzheimer's disease.

The pharmaceutical industry's endorsement of the amyloid hypothesis for Alzheimer's disease appears to be experiencing a resurgence, thanks to Biogen's highly controversial Aduhelm. As another anti-amyloid therapy, the drug recently secured FDA approval despite widespread skepticism regarding its efficacy and intense protests over its price of up to $56,000. Aduhelm is the first new Alzheimer's treatment approved by the FDA since 2003, and the first to claim it can halt disease progression. However, its approval has sparked significant controversy, prompting multiple FDA advisory committee members to resign in protest.

Reference: Roche engaged in talks with FDA for Alzheimer’s drug candidate