Within days, federal regulators will decide whether to approve the first new drug for Alzheimer’s disease in nearly two decades, a controversial medicine from Cambridge-based Biogen that seems to have as many detractors as proponents.
It’s called aducanumab, and Kirsten Hano is among those hoping it wins approval.
A 1989 graduate of Williams College who lives in Wellesley, Hano once seemed able to do it all: work 10-hour days as an advertising executive; shepherd three sons to extracurricular activities; start a nonprofit group; and play ice hockey weekly with friends. But last November, after several years of finding it increasingly hard to complete routine tasks, she received a staggering diagnosis: early-onset Alzheimer’s.
She was just 53.
“When you get into the situation that I’m in, you’re looking for anything that can help you,” said Hano, now 54, who wants something to slow her cognitive decline while the fatal disease is in the early stages. “The challenge with Alzheimer’s is that there hasn’t been much that actually works, and the fact that there’s something that can work and can extend at least some of your life . . . It gives me much more hope that I can stick around a little while.”
The Food and Drug Administration is scheduled to announce a decision on aducanumab by Monday in one of its most closely watched rulings in years. The stakes couldn’t be higher. Alzheimer’s is the sixth leading cause of death in the United States and currently afflicts an estimated 5.8 million Americans, increasing to 14 million by 2060, according to the Centers for Disease Control and Prevention. About 2 million of those now afflicted are believed to have mild cognitive decline and might qualify for aducanumab, which is intended to slow progression in people with early symptoms.
The backstory of the drug has been marked by soaring hopes and disheartening setbacks that have sent Biogen’s stock valuation swinging by billions of dollars. Biogen is the biggest homegrown drug maker in the state, by head count, with about 2,400 employees. After aducanumab showed promise in 2016, the biotech launched two late-stage trials, but those were halted in March 2019 after an independent monitoring panel concluded the drug didn’t appear to be working.
In a shocking reversal seven months later, Biogen announced that an analysis of additional data had led to the drug’s resurrection. In one trial, people given aducanumab had declined 22 percent more slowly than those who received a placebo. The other trial failed to reach its goal. Nonetheless, Biogen concluded that aducanumab slowed cognitive decline and that the key to effectiveness was giving patients a high enough dose.
But a number of medical experts say Biogen and Eisai, the Japanese drug firm that collaborated on aducanumab, have not proved their case. Skeptics include a panel of outside experts that advises the FDA and concluded overwhelmingly in a nonbinding vote last November that the companies — and some agency staffers who gave the drug a glowing appraisal — cherry-picked positive data and jettisoned negative results.
“I don’t think that there’s any evidence that the drug works,” said Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School and one of 10 experts on the 11-member advisory committee. “And there’s a lot of good evidence out there that the drug just doesn’t work.”
Critics say giving aducanumab the green light would erode the FDA’s credibility and could hinder development of other Alzheimer’s medicines.
The FDA has approved five medications to treat the disease’s cognitive and memory symptoms — the most recent in 2003 — despite billions of dollars invested in research. Those drugs typically delay the decline for several months. And none address the underlying causes of the disease, as aducanumab is meant to do. Patients would receive the drug intravenously for about an hour every four weeks, unlike older drugs like Namenda and Aricept, which come in pill form.
Aducanumab is a monoclonal antibody made from the immune cells of older people with no (or uncommonly slow) cognitive decline. Researchers designed it to remove a sticky substance called beta amyloid that accumulates in the brains of Alzheimer’s patients, although experts disagree about whether beta amyloid causes the disease or results from it.
Given how common and devastating Alzheimer’s is, a safe and effective treatment would almost certainly be a multibillion-dollar blockbuster. Alzheimer’s has been a graveyard for therapies that showed early promise but fizzled out in trials. In a 2018 report, the pharmaceutical industry said there were 146 unsuccessful efforts to develop treatments for Alzheimer’s in the 20-year period ending in 2017.
No one knows the financial stakes better than Biogen, which has a market value of $40 billion.
Biogen chief executive Michel Vounatsos said in an earnings call in April that his firm is ready to quickly roll out the drug in more than 600 clinical sites in the United States if given the go-ahead. It’s even built a $1 billion plant in Switzerland to help manufacture it.
Much of the controversy about aducanumab stems from the conflicting outcomes of the trials. The FDA typically requires two convincing studies for a medication to be approved, but has made exceptions, particularly for deadly or devastating diseases for which there are no effective treatments.
Dr. Stephen Salloway, director of neurology and the Memory and Aging Program at Butler Hospital in Providence and a professor at Brown University, participated in the clinical trials at his hospital and was impressed. He said that he treated 17 patients and that 10 didn’t decline while on the medicine.
“This is the first time in more than 100 trials for Alzheimer’s that we noticed this type of clinical effect,” he said.
One recipient of the drug at Butler is Dr. Henry Magendantz, a retired obstetrician-gynecologist who got his first dosage about five years ago, according to his wife, Kathy Jellison. For the first 3½ years, she said, the infusions kept his Alzheimer’s disease from advancing. He was able to volunteer at a free Providence medical clinic, travel to London with her, and enjoy their nine grandchildren.
“I think it’s a miracle drug, quite frankly,” she said.
After the trial was halted and he temporarily stopped getting infusions, she said, Magendantz’s dementia worsened. He now lives in an assisted-living center.
But several experts say that the evidence is muddled at best and that the FDA should insist Biogen mount a third late-stage trial.
Aducanumab is not without risks to patients, said Dr. Michael Greicius, director of the Stanford Center for Memory Disorders. Three out of 10 patients who received a high dose had brain swelling detectable on an MRI scan, he said. This didn’t usually cause serious symptoms but led to confusion and falls in some patients.
If aducanumab is approved, Greicius added, it could delay the development of better drugs by five to 10 years. “Everyone will want to be on this drug because the FDA approved it,” he said, making it hard to recruit Alzheimer’s patients for other studies where some volunteers would get a placebo.
An influential drug-pricing watchdog group recently took a dim view of aducanumab. Citing the conflicting study results, the Boston-based Institute for Clinical and Economic Review said in a draft report that, if approved, the drug should be priced at $2,500 to $8,300 annually, given its modest benefits and risks for complications. That’s a fraction of the $50,000 some analysts predicted it could command.
With such polarized views, some analysts predict drug regulators may take a middle path.
Nearly half of 47 biotech investors recently surveyed by RBC Capital Markets expected the FDA to reach a compromise. That could mean an approval with strict limitations on eligibility for the drug, or requiring Biogen conduct a third, tie-breaking trial whose results would determine whether the approval would be rescinded or changed.
Hano, the former advertising executive who now has Alzheimer’s, said she just hopes regulators make aducanumab available to her — and soon. She currently takes one of the older drugs, the generic version of Aricept, but says she can’t work anymore. Hano wants to be around for her family as long as possible.
“Anything they can do to eke out any bit of time for people is worth it,” she said.
Jonathan Saltzman can be reached at firstname.lastname@example.org.