New Drug Shows Promise Against Alzheimer’s

After a string of failures in Alzheimer’s disease treatment, drug companies say they might have a medication that both clears toxic amyloid proteins from the brain and significantly slows the rate of a patient’s mental decline.

In early July, drugmakers Biogen and Eisai set the Alzheimer’s world abuzz with news that they had an experimental drug — BAN2401 — that had shown positive results in human patients. At the time, they put out a news release touting their results as a first, and promised to show the actual study data at an upcoming medical meeting.

On Wednesday, they finally released the results everyone was waiting to see, and they were greeted by cautious optimism at the 2018 Alzheimer’s Association International Conference in Chicago.

The company showed that over 18 months on the highest dose of the drug — 10 mg per kilogram of body weight given twice a month by IV — patients with mild cognitive impairment and early Alzheimer’s disease had big reductions of beta amyloid in their brains. They had about 93% less beta amyloid, compared with people in the study taking a placebo, or dummy medication. They also showed less decline on congitive tests than patients who were taking a placebo.

Beta amyloid is a protein that is the main component of sticky plaques that build up in the brains of Alzheimer’s patients. It’s considered a signature, and a likely cause, of the disease.

“Beta amyloid is a normal protein. We all have it,” says Ronald Petersen, MD, PhD, who directs the Mayo Clinic Alzheimer’s Disease Research Center in Rochester, MN.

In Alzheimer’s disease, the body’s normal process for getting beta amyloid out of the brain goes awry.

In healthy brains, beta amyloid gets snipped in the middle by an enzyme called alpha secretase. The two pieces get cleared from the brain and everything is OK, Petersen says. In Alzheimer’s disease, two other enzymes–beta secretase and gamma secretase–cut the protein in places it wouldn’t normally be, leaving fragments that the body doesn’t recognize or know how to get rid of, he says.

“It’s these toxic fragments that start to accumulate in the brain to form plaques,” says Petersen, who was not involved in the study.

BAN2401 is a monoclonal antibody, and it is particularly good at sopping up toxic beta amyloid fragments, called protofibrils.

The science behind the drug comes from a family in a small village in northern Sweden. The family had an inherited genetic mutation–now called the Arctic mutation–which caused them to have high levels of protofibrils in their brains and a very high risk for Alzheimer’s disease. Scientists guessed that clearing these toxic fragments could help heal the brain.

The study showed that BAN2401 was indeed very good at removing beta amyloid.

No drug has ever demonstrated both the ability to clear beta amyloid and slow the progression of the disease in such a short period of time, just 18 months.

In a statement, the Alzheimer’s Association said the research indicates “that amyloid remains an important therapeutic target to pursue in Alzheimer’s disease.”

But the jury is still out on whether that will translate into meaningful benefits for patients.