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By Mark Tosczak

High Point-based vTv Therapeutics on Tuesday announced that its experimental Alzheimer’s drug, azeliragon, failed to slow the progress of the disease.

The company has been working with the drug for almost 20 years, hoping for a breakthrough in treating Alzheimer’s disease, which afflicts 5.7 million Americans and is expected to cost $277 billion this year. No new Alzheimer’s drugs have been approved in 14 years.

Azeliragon was being tested in two Phase 3 trials, each with about 400 patients who’ve been diagnosed with mild Alzheimer’s disease. Phase 3 trials are the last studies done before a company can seek Food and Drug Administration approval for a new medicine.

The results announced this week of the first of those trials mean the company won’t be seeking FDA approval.

Compared to a placebo, the company said, people taking the drug didn’t improve in either cognitive or functional outcomes. Patients treated with azeliragon had a 4.4-point decline from baseline on the Alzheimer’s Disease Assessment Scale-cognitive subscale and a 1.6-point decline on the Clinical Dementia Rating Scale Sum of Boxes.

Patients on a placebo had declines of 3.3 points and 1.6 points on each of those scales respectively. The difference in results between the drug and placebo weren’t statistically significant, the company said.

“We will continue to analyze the datasets and trends within subgroups from both Part A and Part B to determine if there are potential benefits or future uses and applications for azeliragon,” said Steve Holcombe, chief executive officer, vTv Therapeutics.

Uphill struggle

vTv is just the latest company to discover how difficult it is to develop new Alzheimer’s drugs. Since the last new drug was OK’d 14 years ago, one drug candidate after another has failed.

In January, Chapel Hill-based Zinfandel Pharmaceuticals announced it was discontinuing a large Phase 3 trial of the drug pioglitazone. Pharma giant Pfizer announced earlier this year it was getting out of research efforts focused on Alzheimer’s and other neurological disorders.

The traditional approach to drug development — finding a promising compound and then pushing it through human testing in hopes of bringing it to market as quickly as possible — “does not work very well for neurodegenerative disease disorders,” said Dr. Dan Kaufer, director of the N.C. Memory Disorders Program at UNC.

This, along with other failed Phase 3 trials, shows that more work needs to be done before large, expensive human trials are conducted, Kaufer said.

“Here we are spending millions and millions of dollars on these huge trials that are disappointing,” he said. “We need to spend more time making sure we’re on the right track.”

Pharmaceutical companies, Kaufer said, are motivated by the potential payoff of a new successful Alzheimer’s drug, which he estimated could be worth $10 to 15 billion annually in drug sales.

Public health approach

The need for new treatments for the disease is only going to grow more pressing in the coming decades, as a growing number of aging baby boomers afflicted with Alzheimer’s, which causes memory loss, cognitive and behavioral problems. Deaths from Alzheimer’s increased 123 percent from 2000 to 2015.

The Alzheimer’s Association projects that in North Carolina this year, some 170,000 people have the deadly disease. By 2025, that number is expected to grow to 210,000 — a 23.5 percent increase. Nationally, by 2050, Alzheimer’s is expected to afflict 13.8 million and cost an estimated about $1.1 trillion annually.

Given the paucity of effective drugs to treat the condition, Kaufer said more effort has to be put into prevention.

“From a treatment point of view, the best data we have for lowering someone’s risk for Alzheimer’s is treating [their] high blood pressure,” Kaufer said. Prevention efforts much earlier in life — when people are middle aged or younger — might be a more effective way to stem the coming tide of Alzheimer’s cases. “This needs to become a public health priority.”

The General Assembly has provided funding to create a statewide brain health registry. That effort is set to launch in the next few months.

Also on Tuesday, the National Institutes of Health announced that a group of researchers had reached consensus on a biologically based definition of Alzheimer’s, based on physically measurable changes to the brain. The hope is that this new framework will help scientists make faster progress toward new treatments.

In March, President Trump signed a bill increasing federal funding for Alzheimer’s research from $1.4 billion to $1.8 billion.

vTv Therapeutics’ stock (NASDAQ: VTVT) lost 78 percent of its value after the announcement, plunging from a Monday closing price of $3.26 to $0.71 per share by the close of trading Tuesday.

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Mark Tosczak

Mark Tosczak has worked as a writer and communications professional for more than 20 years, including stints as a newspaper reporter and editor, think tank communications director, marketing agency vice...