Alzheimer’s drug opens new path to treatment

The Yomiuri Shimbun
A doctor, right, explains the results of a brain imaging examination to a patient at Alz Clinic Tokyo in Chiyoda Ward, Tokyo.

The approval of a new Alzheimer’s drug by the U.S. Food and Drug Administration is a major step in the fight against dementia, but challenges remain for getting it into practical use.

The FDA has recently approved the drug aducanumab to treat Alzheimer’s disease, the most common form of dementia, which affects more than 50 million people worldwide.

This is the first drug in the world to successfully suppress cognitive decline by removing the substances in the brain believed to cause the disease. Aducanumab is also going through screening processes in Japan and Europe.

Removing causative substance

“Approval in Japan may be a ways off, but I want to take the new drug as soon as possible for the sake of my family,” said an 81-year-old man who runs a company, expressing his excitement about the approval of aducanumab in the United States.

The man is a patient at a Tokyo clinic that specializes in dementia. Last spring, he was told he had mild cognitive impairment, the stage preceding dementia.

There are no drugs to treat his condition, and while he exercises and watches his diet, he is worried that his memory loss will worsen.

Alzheimer’s disease, which accounts for 60% to 70% of dementia cases, involves the accumulation of a protein called amyloid beta in the brain over a period of 10-20 years before onset.

The disease is thought to gradually destroy neurons in the brain, leading to cognitive decline in areas such as memory and judgment.

Until now, drugs have improved symptoms only temporarily, with the effects lasting about a year. The new drug, jointly developed by Japanese pharmaceutical company Eisai Co. and U.S. pharmaceutical company Biogen Inc., acts directly on amyloid beta, which is believed to be the cause of Alzheimer’s.

A monthly infusion removes amyloid beta from the brain, preventing damage to neurons with the expected result of suppressing the progression of the disease over the long term.

Learning from failure

Dementia has become a common challenge in the world. As many countries now have aging populations, it is estimated that 150 million people will have dementia by 2050. Drug companies have been competing fiercely to develop something that can provide a radical cure, only to be met with repeated failure.

Yet these failures have provided some lessons.

In patients with advanced dementia, many neurons are already dead, so removing the causative substances does not restore their condition. Therefore, drug companies turned their attention to early-stage patients and people before onset, who have suffered less neuron damage.

For aducanumab, clinical trials were conducted on patients with mild Alzheimer’s disease not long after onset and on people with pre-onset mild cognitive impairment.

The companies suspended the trials because they believed it was unlikely that efficacy would be confirmed, but upon reviewing the data, they found that patients who took the drug experienced a 22% improvement in their symptom after 18 months.

In July last year, they applied for approval with the FDA.

With conditions

The FDA’s assessment stated that “there is substantial evidence that [aducanumab] reduces amyloid beta plaques in the brain and that the reduction in these plaques is reasonably likely to predict important benefits to patients.”

However, several experts said that the drug’s efficacy had not been sufficiently demonstrated. Therefore, the FDA granted it “accelerated approval,” which allows new drugs for serious diseases with no available treatments to be used quickly, on the condition that efficacy be reevaluated through additional clinical trials.

If the drug’s efficacy cannot be confirmed, approval may be withdrawn.

In addition to aducanumab, other new drugs to eliminate amyloid beta are being developed.

Clinical trials mainly of early-stage patients are underway in Japan for drugs including gantenerumab from Japanese firm Chugai Pharmaceutical Co. and others, and donanemab from Eli Lilly and Co. of the United States.

“Although efficacy needs to be confirmed over the long term, it will bring hope to patients waiting for a treatment,” said Atsushi Iwata, director of the neurology department at the Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology. “It is also significant in encouraging the development of future dementia drugs.”