Arizona drug studies target Alzheimer’s earlier

Though recent studies question the effectiveness of new drugs to combat Alzheimer’s disease, local drug trials continue. Wochit

Two recent studies cast a cloud over the effectiveness of new drugs to combat Alzheimer’s disease, but ongoing drug trials continue as researchers hope that an effective treatment can be found.


Despite great hope and hundreds of millions of dollars spent to develop an experimental drug viewed as a candidate to slow Alzheimer’s disease, a late-stage medical study revealed the scientific hard facts late last year.

The drug, solanezumab, worked no better than a placebo.

Alzheimer’s researchers got another dose of bad news Tuesday when drugmaker Merck announced it would halt a late-stage study of another drug, verubecestat, due to lack of effectiveness.

“Any time a drug trial doesn’t pan out, especially ones that reach Phase 3, people feel understandably disappointed,” said Dan Lawler, executive director of the Alzheimer’s Association’s Desert Southwest Chapter.

What they’re testing

Some scientists have long theorized that a type of protein, beta-amyloid, accumulates in the brain and leads to memory and thinking problems, but other scientists have questioned the “amyloid hypothesis.” And so far, no drugs developed to attack beta-amyloid have proven successful at combating cognitive decline in patients with the mind-robbing disease.

Phoenix-based Banner Alzheimer’s Institute, which launched a decade ago, has become a leading proponent of the idea that giving at-risk patients drugs earlier — before memory and thinking problems surface — could be a possible way to attack the disease.

Several studies are testing that very idea, including two clinical trials spearheaded by Banner that are testing anti-amyloid drugs on people who face high genetic risk but no symptoms. Those studies — one involving an extended family in Colombia and a second involving healthy older adults who carry a high genetic risk of developing Alzheimer’s disease — are testing anti-amyloid drugs on patients before memory and thinking problems occur.

Dr. Eric Reiman, executive director of Banner Alzheimer’s Institute, acknowledged that Alzheimer’s drug trials “are not for the faint-hearted.”

“There is no guarantee that any of these will work,” Reiman said. “I believe we have at least a 50 percent chance that one of them works,” by 2025.

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What happened?

The 2,100-person study of Eli Lilly’s experimental drug solanezumab, designed to bind to and clear beta-amyloid, failed to benefit patients who had mild dementia. Merck’s verubecestat, designed to target an enzyme that produces beta-amyloid, did not prove effective in a study of about 2,000 people with mild to moderate Alzheimer’s.

In a recent article in the journal Nature, Reiman argued that there are possible explanations for solanezumab’s failure, such as doses that were too low or administered too late, after the disease had marched on the brain.

He said research of anti-amyloid treatments must continue, both in people with memory and thinking problems and in symptom-free individuals with a genetic risk of Alzheimer’s.

“Although the possibility remains that critical elements of the amyloid hypothesis are simply wrong, it would be premature to draw that conclusion until different (anti-amyloid) treatments have failed to work, even in unimpaired people at increased risk when the disease is less extensive,” Reiman wrote in the Nature article.

Two studies underway

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Banner Alzheimer’s Institute is studying an anti-amyloid drug, crenezumab, in an extended family of Colombia residents. These family members carry a rare genetic mutation that guarantees they will get Alzheimer’s disease, usually beginning in their mid-40s.

The study seeks to recruit about 300 family members, including 200 who carry the Alzheimer’s mutation and 100 without the mutation. Family members who carry a mutated version of the gene that guarantees early-onset Alzheimer’s will be given either crenezumab or a placebo. The other 100 non-mutation carriers will also get a placebo.

Reiman said he expects enrollment in the Colombia trial will be completed by this spring.

Banner also is also recruiting for a second study of people who carry two copies of an Alzheimer’s risk gene, APOE4. The Generation study will recruit older adults who carry two copies of the risk gene but have not shown signs of dementia.

The study is funded with a $33.2 million grant from the National Institute on Aging and $15 million from Banner Alzheimer’s Foundation and the Alzheimer’s Association. Drugmakers Novartis and Amgen will contribute two experimental drugs, called CAD106 and CNP520.

“Enrollment has been slow but methodical,” said Reiman, adding that Banner and Amgen expect to add more clinical trial sites to the study. “We think enrollment will accelerate through the end of this year.”

A third Alzheimer’s prevention study led by Harvard University researchers also is recruiting local patients. The study, called anti-amyloid treatment in asymptomatic Alzheimer’s, or A4, also will study solanezumab on older adults without symptoms.

Dr. Reisa Sperling of Massachusetts General Hospital and Harvard Medical School admits that last November’s failure of Eli Lilly’s solanezumab study was disappointing. She said her team is still assessing the data from the study and believes the key still remains earlier treatment — before memory and thinking problems occur.

“We know amyloid is building in the brain for more than a decade,” Sperling said.

Aging Boomers at risk?

Reiman said several other prevention trials are underway at Banner and at universities across the nation. In many ways, it’s a race to provide an effective treatments for an aging population.

About 5 million Americans live with Alzheimer’s disease or other dementia, and projections suggest that number could triple by 2050 as Baby Boomers age. However, a University of Michigan-led research team last November reported some good news: The percentage of adults age 65 and older with dementia declined from 11.6 percent in 2000 to 8.8 percent in 2012.

Lawler, of the Alzheimer’s Association, said Arizona families afflicted with Alzheimer’s disease are intrigued by these prevention trials — testing experimental drugs on people who carry no symptoms.

Lawler said his organization has pushed for more research involving both people with dementia and their healthy family members.

Even unsuccessful drugs trials like solanezumab provide scientists new clues about the disease, Lawler said.

“There is a lot of excitement with the state of research today and what is to come in the next five to 10 years,” Lawler said. “We are an epicenter of research here and knowledge of what drugs are being developed. There is a lot of excitement on what could be coming.”


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