March 31, 2015
Early testing of a new drug showed promise in reducing declines in memory and thinking skills in people in the early stages of Alzheimer’s disease. The drug, called aducanumab, also reduced levels in the brain of beta-amyloid, the toxic protein that builds up and forms telltale plaques in the brains of those with Alzheimer’s.
Many experts believe that beta-amyloid plaque plays a critical role in the development of Alzheimer’s disease. But so far, drugs to combat Alzheimer’s progression have shown only very limited benefit at best.
“This is the first time an investigational drug for Alzheimer’s disease has demonstrated a statistically significant reduction on amyloid plaque as well as a statistically significant slowing of clinical impairment in patients with mild disease,” said Dr. Alfred Sandrock, the chief medical officer at Biogen Idec, the company that makes the drug. “Based on these results, we are advancing the aducanumab clinical program to Phase 3 with plans to initiate enrollment later this year.”
Phase 3 trials are conducted in large numbers of people and are a critical step in making a drug commercially available. But caution is urged. Many drugs that have shown promise against Alzheimer’s in early trials have turned out to be ineffective or, worse, dangerous in late-stage testing involving large numbers of people.
The findings, presented at the 12th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders in Nice, France, underscore the importance of continued research to find new and more effective treatments for Alzheimer’s. Currently available drugs for the disease may ease symptoms for a time but do nothing to stop the relentless progression of disease.
The current study was conducted in 166 men and women in the early stages of Alzheimer’s disease. All had some evidence of plaque buildup in their brains. Some got the new drug at varying doses, while one group got a placebo, over the period of about a year. Neither doctors nor patients knew who was getting the real drug, and who was getting the dummy drug.
The researchers found that the higher the dose of drug, the less people with Alzheimer’s declined on tests of memory and thinking skills. In one common memory test, the Mini Mental State Examination, for example, which is scored on a 30-point scale, with lower scores representing greater cognitive impairment, people taking the placebo declined, on average, by 3.14 points over the course of a year. The decline was only 0.58 points in those taking the highest dose of drug, and 0.75 points in those getting a medium dose.
Researchers also performed brain scans using PET imaging and radioactive tracers that bind to beta-amyloid plaque on the study participants. They found that treatment with aducanumab resulted in a significant reduction in plaque buildup; the higher the dose and the longer the drug was given, the greater the reduction in plaque. The brains of those getting the placebo were virtually unchanged.
Most of those in the study tolerated the drug reasonably well, although on brain scans some brain swelling was detected in those taking the higher doses. The brain swelling did not produce symptoms but can be a sign of impending, more serious problems. It was most prominent in those who carried the APOE-E4 gene, which increases the risk of developing Alzheimer’s disease.
Headaches occurred in 22 percent of patients receiving aducanumab compared to 5 percent in the placebo groups and appeared to be dependent on dose. Three deaths occurred during the study, but none were considered to be treatment related.
Aducanumab is what’s known as a monoclonal antibody, a drug that targets clumps of beta-amyloid in the brain. Various other monoclonal antibodies have undergone late-stage testing, but none have yet proven safe and effective for treating or preventing Alzheimer’s.
Evidence suggests that brain changes in Alzheimer’s typically begin years prior to the memory loss and other symptoms that lead to a clinical diagnosis. As the disease progresses, declines in memory, behavioral changes and problems with completing day-to-day tasks become more evident.
Many experts think that drugs to combat Alzheimer’s progression may be most effective at the earliest stages, before symptoms become evident and damage to the brain becomes widespread. More research to understand what causes Alzheimer’s, and how it might be treated, is critical for finding a cure for a disease that is estimated to affect more than 25 million people worldwide.
Source: 12th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders in Nice, France; Biogen.