Alzheimer’s Drug Granted FDA Breakthrough Designation as Space Heats Up

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Global biotech giant Roche has announced that the U.S. Food and Drug Administration (FDA) has awarded its candidate Alzheimer's Disease drug gantenerumab Breakthrough Therapy Designation, bringing it closer to finally getting a full FDA approval. 

The decision is based on promising results from the ongoing Marguerite RoAD and SCarlet RoAD open-label extension trials, showing a significant reduction in brain amyloid plaque in Alzheimer's patients. Findings from both trials have been incorporated into the ongoing global Phase III trials GRADUATE I and II. The pivotal GRADUATE trials are assessing the effect of gantenerumab in over 2,000 participants over the last two years. 

Gantenerumab is an IgG1 antibody that can remove brain amyloid plaques by binding to aggregated beta-amyloid structures. The GRADUATE trials are looking into the safety and efficacy of the drug in patients diagnosed with prodromal-to-mild Alzheimer's Disease. The massive study covers 250 centers in over 30 countries, where patients are given a 1,020 mg dose of gantenerumab monthly with optimized titration. Both GRADUATE 1 and 2 are expected to be done by mid-2022. 

Roche started the SCarlet RoAD trial in 2012, during which a dose of 105 or 225 mg gantenerumab was injected subcutaneously on 799 participants in 159 centers for two years, with the option of an extension for another two years. Co-primary endpoints were the Clinical Dementia Rating Sum of Boxes (CDR-SOB) and the change in brain amyloid levels as measured by positron emission tomography (PET) scan. It was halted in 2014 after it reported no efficacy on primary or secondary endpoints but later decided to extend the trial with participants given a higher dose of 1,200 mg. 

Meanwhile, the Marguerite RoAD trial started in March 2014 on 1,000 patients with mild AD. It stopped enrolling at 389 participants in October 2016 following an interim futility analysis, similar to SCarlet RoAD. It later shifted to an open-label extension trial, where patients were titrated to a higher dose of 1,200 mg gantenerumab.

In 2018, Roche reported that both studies at 1,200 mg lowered brain amyloid by an average of 59 centiloid on florbetapir PET. A subsequent report based on the third year of extension showed that of the 30 participants who were observed, 80% saw a reduction in their amyloid load. 

"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," said Levi Garraway, M.D., Ph.D., the chief medical officer and head of global product development at 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," added Dr. Garraway. 

Alzheimer's Disease is a progressive and fatal disease that affects memory, communication, and cognitive skills. It is the most common type of dementia, affecting over 55 million worldwide. Around 10 million people are diagnosed with AD every year.

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