Did It or Didn’t It?
There is sharp division among experts over whether an experimental Alzheimer’s drug has demonstrated enough evidence of effectiveness to obtain FDA approval. Biogen of Cambridge, Massachusetts, and Eisai Company of Tokyo, Japan, claim that aducanumab is the first drug to slow mental decline from Alzheimer’s disease, reported Marilynn Marchione of the Associated Press, but mixed results in clinical trials have raised concerns.
Earlier in 2019, the drug did not seem to be working in two studies. In October it seemed to be effective at a high dose. During a presentation at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) in San Diego the first week of December, the developers led some experts to believe that the drug deserves serious consideration, while others were dubious.
According to the AP story, “Changes made during the study and unusual analyses of the data made the results hard to interpret. And the newly released results showed the drug made only a very small difference in thinking skills in one study and none in the other…Alzheimer’s patients and families are desperate for any help, no matter how small, adding pressure on the Food and Drug Administration to approve something.”
Mayo Clinic’s Dr. David Knopman, who was involved in one of the studies, said, “I don’t see how you can conclude anything other than that another trial needs to be done.”
Laurie Ryan, a dementia scientist at the National Institute on Aging, added, “We need more evidence.” However, Dr. Paul Aisen, a dementia specialist at the University of Southern California, said results were “consistent and positive” in showing a benefit at a high dose — “a truly major advance.”
Aducanumab is designed to help the body clear harmful plaques, or protein clumps, from the brain. More than 5 million people in the U.S. and millions more worldwide have Alzheimer’s. Drugs currently on the market only temporarily ease symptoms and cannot slow the loss of memory and thinking skills, but approving a drug that does not demonstrate effectiveness could create financial and medical risks while reducing the incentive to develop better treatments.
Biogen and Eisai did two studies, each enrolling about 1,650 people with mild cognitive impairment or mild dementia from Alzheimer’s. People with a gene that raises their risk of the disease began on a lower dose, because they have a greater chance of suffering inflammation in the brain from medicines that target plaque. As the studies continued and concern about this side effect abated, the rules were changed to enable these patients to have a higher dose.
According to Biogen vice president, Samantha Budd Haeberlein, more people got the higher dose in one study, helping to explain why it succeeded and the other one failed. Independent experts were skeptical of doing the analysis that way. Additionally, patients in the placebo group got worse in the positive study than in the one that failed.
Dr. Howard Fillit, chief science officer of the Alzheimer’s Drug Discovery Foundation, said, “It’s hard to know exactly what happened here. I don’t see how the FDA could approve it.”
There were also questions about the size of any benefit from the drug. It did not reverse decline, only slowed the rate of it compared to the placebo group by 22 percent in one study. That only meant a difference of 0.39 on an 18-point score of thinking skills. Fillit described it as a small amount.
Maria Carrillo, chief science officer at the Alzheimer’s Association, said it was “the largest reduction that we’ve seen to date. It may mean that they remember their loved ones a little longer. It is worthy of significant, rigorous exploration and review by the FDA. This is an important moment for the Alzheimer’s community.”
While some doctors and caregivers are convinced that the drug helped, some experts are still skeptical. They feel that more testing is needed.
