Promising Drug, Gantenerumab, Fails to Prevent Alzheimer’s Onset

January 23, 2015

A promising investigational drug called gantenerumab failed to stem the slide into Alzheimer’s for people at high risk of developing the disease, a late-stage study found. The results highlight the difficulty of developing effective therapies for combatting Alzheimer’s and underscore the pressing need for ongoing research into the causes and treatments of the memory-robbing illness.

Gantenerumab is one of several drugs currently under investigation for treating or warding off the onset of Alzheimer’s. Current medications for Alzheimer’s may ease symptoms for a time but do not get at the root cause of disease or stop its progression.

The drug had shown promise in earlier, smaller trials in people in the earliest stages of Alzheimer’s. But in the current study, a large study known as the ScarletRoad trial, the drug failed to show benefit compared to a placebo.

“We are disappointed with these study results because people with early stage Alzheimer’s need new medicines that delay disease progression,” said Dr. Sandra Horning, chief medical officer at Roche, the company that is developing the drug.

Gantenerumab is what’s known as a monoclonal antibody, a type of drug that zeroes in on the toxic beta-amyloid that builds up in the brains of those with Alzheimer’s. As levels of beta-amyloid rise, it clumps to form hard plaques in areas of the brain critical for memory and thinking, and symptoms of dementia become increasingly apparent.

Alzheimer’s is a progressive illness that is thought to begin 10 to 20 years before the onset of symptoms like memory loss. Experts have been hopeful that drugs like gantenerumab that are aimed at stemming the disease’s progression may be most effective at an early stage, before damage to the brain becomes extensive.

So for this study, they recruited 799 men and women who were in a so-called prodromal stage, thought to be a precursor to Alzheimer’s. Many had memory and thinking problems, but their symptoms were not severe enough to qualify as full-blown Alzheimer’s.

But frustratingly, in this study, gantenerumab failed to prevent the buildup of plaque, or to ward off the onset of Alzheimer’s.

“This is the first Phase 3 trial to evaluate a potential disease-modifying medicine in this early prodromal stage of Alzheimer’s disease,” Dr. Horning said.

The company is hoping to learn more from continued analysis of the current study results, and is continuing another study of gantenerumab in patients with early-stage Alzheimer’s. It is also investigating additional drugs, including crenezumab, another monoclonal antibody that targets beta-amyloid, and RG1577, which targets other pathways in the progression to Alzheimer’s.

Other companies are exploring additional drugs that target beta-amyloid, including solanezumab (from Eli Lilly) and a drug called BIIB037 (from Biogen). Other therapies involving antibodies have also been tried to reduce levels of beta-amyloid in the brains of those with Alzheimer’s disease, but some patients receiving the earlier treatments developed brain inflammation. In the current study, gantenerumab appeared to be relatively safe.

The disappointing results with this and other investigational therapies highlight the need for more effective ways to target Alzheimer’s onset and progression. Better understanding of the underlying causes of Alzheimer’s should lead to better treatments and, one day, a cure for a disease that affects some 44 million people worldwide.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source: Roche Drug Company.


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