Correction: An earlier version of this article misstated what the the costs associated with Alzheimer’s disease will be by the year 2040. This version has been corrected.
Pharmaceutical researchers on Wednesday presented new data from the clinical trials of three drugs that, the scientists said, show promise for slowing the progression of Alzheimer’s disease.
Researchers presented new analyses of research data on drugs produced by Eli Lilly, Roche and Biogen. All of the drugs involve using monoclonal antibodies, which are genetically engineered to mimic actions carried out by the body’s immune system, and all of them target the accumulation in the brain of an abnormal protein known as beta amyloid, which forms insoluble plaques that can trigger the destruction of surrounding brain cells.
But in a field in which almost every drug has failed to do what its backers initially hoped, several scientists also cautioned against putting too much emphasis on data that showed incremental progress.
The results — presented at the Alzheimer’s Association International Conference, held in Washington — offered a glimpse into an expensive and frustrating hunt for medications to tackle a costly and terrifying disease. More than 5 million people in the United States have Alzheimer’s, and the number is expected to reach 13.5 million by the middle of the century. By 2040, when baby boomers will range from 76 to 94 years old, the disease will cost more than $328 billion and account for about 24 percent of Medicare spending.
David Knopman, a physician and vice chairman of the Alzheimer’s Association medical and scientific advisory council, took care to tamp down expectations among patients and their families anxious for a cure.
“To be honest, these results are not going to be something they can get next week,” Knopman said. “But what you’re hearing here represents solid advances, both in technology, in conceptualization and — at a practical level, as two of the studies talk about — in figuring out what’s the right dose.”
Eli Lilly’s researchers said their analysis of the drug solanezumab showed the potential value of a “delayed start” approach to clinical trials as a way of determining a drug’s success in slowing the progression of a degenerative brain disease. And the study lent additional support to the view that identifying signs of Alzheimer’s early and beginning early treatment could make a significant difference for people who suffer from dementia.
Previous studies have been ineffective at treating Alzheimer’s disease. But amid signs that solanezumab could help people in the stages leading up to the disease, the researchers continued to follow a group of participants who had only mild cognitive impairment. The participants — including those who had been on a placebo — received the drug for an additional two years in what amounted to a delayed-start experiment.
In a delayed-start trial, patients are assigned at random to receive the drug or a placebo at the beginning of the study. After a period, however, those who initially received the placebo begin taking the experimental drug. If the drug reduces symptoms only, and the maximum reduction of symptoms is achieved in two months, the later group should catch up to the earlier group and be functioning at a similar level. But if the drug slows the disease’s progression, both groups should benefit, but members of the later group will never catch up because the disease will have progressed while they were receiving the placebo.
In the Eli Lilly analysis, the researchers said the results showed that the treatment differences between the early-start and delayed-start groups did not vanish and that the later group did not catch up with the others — leading scientists also to conclude that there is a potential benefit to starting the drug as early as possible.
Paul Aisen, a physician who heads the Alzheimer’s Therapeutic Research Institute at the University of Southern California at San Diego, said the solanezumab study showed that in people with mild cognitive impairment, the rate of degeneration slowed by about one-third.
Biogen’s drug, aducanumab, which is in development and designed to flush beta amyloid deposits from brains in the early stages of degeneration, has already produced results that appear promising, researchers said. On Wednesday, scientists offered new data suggesting that they had also homed in on a dose for the drug that struck a balance between beneficial effects and negative side effects such as inflammation.
A clinical trial on Roche’s drug, gantenerumab, was halted in December amid signs that it was not going to reach targets for efficacy: Patients who received the drug failed overall to improve on measures of cognitive performance, compared with those who received a placebo. But upon resifting the data, researchers found there was evidence that the patients whose disease was progressing more rapidly might benefit from a higher dose of gantenerumab.
Philip Scheltens, a professor of cognitive neurology and director of the Alzheimer’s Center at the VU University Medical Center in Amsterdam, said the results suggest that the dose of gantenerumab used so far was too low and that the drug should be tested further at higher doses.
Ronald C. Petersen, director of the Mayo Clinic’s Alzheimer’s Disease Research Center, said he was cautiously optimistic about the results for the three drugs. But he said it is becoming clearer that Alzheimer’s resembles a syndrome more than a disease, with multiple pathways and pathologies and therefore no single target to focus on for a possible cure. The likelihood is that several medications will have to be used together for effective treatments, he said.
“It’s not like there’s nothing out there; it’s not like there’s nowhere to go,” said Petersen, who also chairs the national Advisory Council on Alzheimer’s Research, Care and Services. “Clinical trials using antibodies to remove amyloid from the brain are making progress. . . . The thinking is positive; the theme is positive. But the data aren’t there yet to say the drugs are effective.”