FDA Grants Breakthrough Therapy Designation to Gantenerumab

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by Patricia Inacio PhD |

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The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy status to gantenerumab, a human antibody that’s expected to slow or even prevent cognitive decline and memory loss in Alzheimer’s disease.

The FDA designation is intended to accelerate the development and review of candidate therapies with clinical evidence of substantial improvement over approved treatments for serious diseases.

Gantenerumab, developed by Roche and its U.S. affiliate Genentech, is designed to bind and reduce amyloid-beta plaque formation in the brain, a hallmark of Alzheimer’s.

Since it is administered under the skin (subcutaneously), the antibody has the potential to be given to patients at home, according to Roche.

“This Breakthrough Therapy Designation reinforces our confidence in gantenerumab, which would be the first subcutaneous medicine for the treatment of Alzheimer’s disease with the potential for at-home administration,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a press release.

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The program’s features include more intensive FDA guidance throughout treatment development — such as ensuring the efficient design of clinical trials — and eligibility for priority review.

The FDA’s decision was based on clinical data from several studies, including early findings of two open-label extension (OLE) Phase 3 clinical trials, Scarlet RoAD (NCT01224106) and Marguerite RoAD (NCT02051608), and the DIAN-TU-001 Phase 2/3 clinical trial (NCT01760005).

These Phase 3 trials assessed the safety and efficacy of gantenerumab in patients with very early stages — called prodromal — or mild Alzheimer’s disease.

The DIAN-TU-001 study was designed to evaluate the safety and effectiveness of gantenerumab versus a placebo in people with inherited forms of early onset Alzheimer’s disease, irrespective of them showing symptoms. That trial is currently still recruiting participants; more information can be found here.

Previous findings from Scarlet RoAD and Marguerite RoAD have shown that gantenerumab reduced the accumulation of amyloid plaques in the brain of patients with sporadic Alzheimer’s disease, as shown by positron emission tomography (PET) scans.

These findings also were maintained in the DIAN-TU-001 study. In that study, gantenerumab also led to a significant reduction of amyloid plaque formation in the brain compared with a placebo, despite failing to slow cognitive decline or memory loss.

The outcomes of these trials were important for the design of the pivotal placebo-controlled Phase 3 GRADUATE 1 (NCT03444870) and GRADUATE 2 (NCT03443973) studies. They are evaluating gantenerumab in more than 2,000 participants with prodromal or mild Alzheimer’s, with results expected by the end of 2022. GRADUATE 1 is currently recruiting, and more information can be found here.

Further, Roche is conducting additional open-label studies, the Phase 3 Open RoAD (NCT04374253) and the Phase 2 GRADUATION trial (NCT04592341).

Patients who participated in the SCarlet RoAD and Marguerite RoAD trials are eligible to participate in Open RoAD, which will continue to evaluate the safety and tolerability of the long-term administration of gantenerumab.

The GRADUATION study, meanwhile, was designed to evaluate the pharmacodynamics — the movement of a medicine into, through, and out of the body — of the once-weekly administration of gantenerumab in individuals with early Alzheimer’s.

“For more than a decade, we’ve been committed to advancing the science of Alzheimer’s as well as our investigational medicine gantenerumab, and we look forward to delivering a comprehensive and robust data set that furthers our collective understanding of this devastating disease,” Garraway said.