Roche plans 4-year late-stage trial for Alzheimer's candidate while awaiting crucial H2 readout

Roche is gearing up for a four-year phase 3 study of its Alzheimer's drug gantenerumab. One trial site in Florida confirmed to Fierce Biotech that patient screening has already gotten underway for the trial, slated to begin June 24. 

The Swiss pharma's Genentech unit is slated to report on two pivotal trials of gantenerumab in the second half of this year, according to an October 2021 update when the drug received breakthrough therapy designation from the FDA. The two studies, Graduate 1 and 2, comprise more than 2,000 patients with the appearance of initial symptoms or early Alzheimer's across more than 30 countries.

While awaiting that data, the pharma is now recruiting for a new phase 3 trial. The study will test the monoclonal antibody in patients who either don't have Alzheimer's but are at risk or are in the earliest stages of the memory-robbing disease. The four-year trial, dubbed Skyline, will test the drug in 600 patients and compare it to another 600 patients who receive a placebo, according to a Feb. 25 addition to the registry. 

Roche disclosed the news Thursday and said it intends to form a collaboration agreement to work with the Banner Alzheimer’s Institute, Massachusetts General Hospital and the University of Southern California Alzheimer’s Therapeutic Research Institute. Roche characterized the study as a secondary prevention trial. 

RELATED: Roche, Lilly push back against CMS painting their Alzheimer's meds with the same brush as Biogen's Aduhelm

The pharma is working with two Florida trial sites so far on recruiting patients: K2 Medical Research in Orlando and Alzheimer's Research and Treatment Center in Wellington. A K2 representative said some patients have been screened already.

Stifel analysts have recently said they believe gantenerumab has the "least compelling case" of all the late-stage antibody candidates for the neurodegenerative disease currently in development. Roche is trying to shuttle gantenerumab through clinical development at the same time as Eli Lilly's donanemab, but the Indianapolis Big Pharma is likely closer to the finish line with an accelerated approval request already in the works.

Roche shelved gantenerumab in 2014 after a failed phase 3 but brought the candidate back into play in 2018 to test whether a higher dose might produce an effect in patients. Washington University School of Medicine also tested the drug, but, again, it flopped.

In the new phase 3 study in the hopper for June, Roche wants to test the drug in patients 60 to 80 years of age who are cognitively unimpaired but have evidence of amyloid accumulation in their brain, according to the registry in the federal trials database. 

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The primary goal of the study is looking at how patients improved from baseline to year four on a scale that looks at episodic memory, timed executive function and global cognition. 

Patients will be given the choice of dosing either every week or every two weeks, and the option to receive the drug at home. The study will take place in 17 countries. 

Roche added the phase 3 trial to the federal database last week, just 14 days after the company joined Lilly in pushing back against the Centers for Medicare & Medicaid Services' proposal to limit Medicare coverage of Biogen's Aduhelm to only patients enrolled in clinical trials. If passed as currently written, the ruling could also apply to gantenerumab and other mAbs in development that target amyloid.

Following the FDA's controversial approval of Aduhelm in June 2021, Roche was reported to have been in talks with the FDA about gantenerumab. CEO Severin Schwan confirmed in July 2021 that the two parties were talking but didn't elaborate on the nature or outcome of the dialogue.

Editor's note: This story was updated at 12:27 p.m. ET on March 3 to include details from a Roche company announcement.