When the ‘real thing’ becomes a mirage: How patients in Alzheimer’s trials are coping with the treatment’s failure

The disheartening news came when Phil Gutis was already upset, crying to his husband because he was having trouble remembering Abe, their Jack Russell terrier who died last year.

Down in Florida, Geri Taylor was leaving yoga class when her friend’s husband called and said it was over. “I was certain he had made a mistake,” she said.

On the West Coast, most people woke up to the shock that was already reverberating among dozens of clinical trial sites, pummeling a company’s stock price, and erasing the hope that so many patients and caregivers had been so tightly holding onto.

When Biogen and its partner Eisai announced that they were stopping two phase 3 trials of the Alzheimer’s treatment aducanumab because the drug did not appear to be working, it shattered the faith that a truly effective therapy — one that could decelerate the descent that came with the disease — was finally in reach. It ignited reckonings both for Massachusetts-based Biogen and for the underlying scientific theory of Alzheimer’s on which aducanumab was constructed.

But as broadly as the disappointment was felt, the blow to the roughly 3,200 people in the trials and their families was particularly acute. The news a week and a half ago came with the realizations that the drug hadn’t been staving off their neurodegenerative decline, and that there wasn’t another option that could do so into the future.

“Like the rug was pulled out from under us.”

“I felt defeated because I went on the Internet and looked around and there’s just nothing else.”

“I had this overwhelming sense of dread, almost like a hopelessness.”

Biogen was legally obligated to announce the market-moving news publicly, without being able to give participants notice. Supervisors at trial sites rushed to get in touch with patients, but many had already found out through texts or phone calls from friends or had seen the media coverage.

Talking to families that day, said Kris Kauno, the clinical trials supervisor at the University of Washington’s Alzheimer’s Disease Research Center, “was one of the hardest things I have ever had to do.”

Patients who were in the aducanumab trials told STAT that they had been realistic about the prospects for the drug and had tried to brace themselves for disappointment. They knew the dismal success rate of Alzheimer’s studies and had seen Eli Lilly and Roche trials collapse. Their frequent MRIs and PET scans and cognitive testing made clear that this was all one big experiment to see if stripping away clumps of beta-amyloid protein from their brains could safeguard their cognitive capabilities.

They vowed to keep an eye out for other trials and emphasized that this setback was a temporary hit to their outlooks, one from which they were already moving forward.

Still. There was so much excitement for this trial, which was reaching people in the earliest stages of the disease. This time might be different, they were sometimes told by clinicians or advocates of the “amyloid hypothesis,” who reasoned that previous trials of amyloid-clearing drugs hadn’t slowed memory loss — as one would expect if the clumps of protein were causing the disease — because treatment had started too late.

Biogen was pushing the drug in two massive Phase 3 trials, spending fortunes to run them after seeing hopeful signs in previous, smaller trials. That had to be a sign of confidence, right? Plus, some patients felt — and still maintain — that it was working, that if it wasn’t making their memories better, at least it was holding off further erosion.

“For the last 36 months, in almost every conversation I’ve had with every professional from every different spectrum within neurology, everyone seemed to be resting on the success of aducanumab,” said Jeff Borghoff, 54, of Forked River, N.J., a father of three who was diagnosed with Alzheimer’s in March 2016.

It wasn’t just the drug’s potential that was extinguished. For patients — even those who were skeptical about aducanumab’s effectiveness — participating in the trial was an action they could take. It provided a community of trial supervisors and clinicians they saw every month when they got the drug infused. It extended a sense of purpose to a disease that had already robbed them of careers and independence and promised to wick away their identities. Enrolling in a study — and envisioning how it might help future generations — became a part of their new selves.

“When you have Alzheimer’s and you can’t work anymore, it’s a very isolating disease,” said Gutis, of New Hope, Pa., a 57-year-old former New York Times reporter who has written about his experience for the paper. “And once a month, I went down and interacted with people. It was being part of something bigger, which I had been my entire life, you know? And that hurt in some ways more than anything else.”

Already, though, patients and their families said they were recalibrating their attitudes. They vowed to redouble their advocacy and fundraising efforts and stressed how important it was to participate in clinical trials. They would adjust, they said, just like they had been adapting to living with Alzheimer’s, with tricks like a note system on the fridge or installing a location tracker on their cell phones.

“I was feeding the dog like three times,” Debby Rosenkrantz, 65, of Cambridge, Mass., said with a laugh. “He was really happy.”

Rosenkrantz was one of the patients in the trial who sifted for signs that the drug might be helping. She repeated some cognitive tests a few weeks ago and learned that in the year since she was diagnosed, her function hadn’t declined. She didn’t know if she was in the placebo or the treatment arm of the trial, but to her, that signaled that she was getting the drug.

“It was like, ‘Yes! I’m on the real thing!’” she said.

Now, Rosenkrantz finds herself leaning on the fact that her disease hadn’t advanced to give herself a more positive viewpoint. She meditates and does puzzles, which she knows might not actually make a difference, but they make her feel better. She has stopped driving — not because she couldn’t operate a car, but because she wouldn’t remember where she parked — but still takes the bus.

“I worry that without this medication I’m going to lose the independence that I do have, the pleasures that I do have,” she said.

Others saw their diseases progressing even as they continued taking aducanumab. Taylor, 75, who spends the winter in Jupiter, Fla., enrolled in the phase 1B trial of the drug four years ago and kept receiving it through an open-label extension. She said she couldn’t be sure how the drug was affecting her, but that her struggles to remember dates or do simple math kept getting worse. So while the suddenness of the trials’ cancelation came as a shock, “it didn’t hit me emotionally in terms of a loss,” she said.

For some patients, learning that aducanumab was not effective also meant facing a future without a brake on their declines. Some participants started to rethink what their lives might look like.

Deb, 61, who lives in Maine and works in the nonprofit sector, said she had planned on working until she was 70. Now, she’s mulling retiring at 65. She wants to give herself time before she loses more of her memory and her autonomy. (She asked that her last name not be used because she worried about how people, particularly at work, would view her if they knew she had Alzheimer’s.)

“I’m going to ride my horses,” she said. “I’m going to make some changes in my stress levels. I’m going to take whatever I’ve got left for me.”

For Jesse Rhoden, 71, of Springboro, Ohio, finding out that the trial was over landed not just with shock but confusion. Rhoden was certain aducanumab was working for him.

He was able to have technical conversations with old colleagues, without having to concentrate too much. He stopped getting so confused about why he had walked into a certain room. And when he had to pause infusions after some side effects, he felt like his disease started progressing again.

“It was like it was putting it on hold,” he said.

Rhoden, who watched his sister die of Alzheimer’s, had expected to stay on aducanumab through the open-label phase. Now, his expectation of being on the drug for years has flipped into wondering how many years he’ll be alive for.

“It’s like somebody calling you and saying, ‘You know, this thing isn’t going to work, and we’re going to stop it, and now you’re just going to start deteriorating,’” he said about learning the news.

Rhoden said by phone last week that he would look for other trials. But that afternoon his plan was simpler: a trip to the park with his grandson.