When Jeff Borghoff saw the article Tuesday morning, the first thing he did was double-check the date it was published. He thought it might be years old, not a breaking story.
In Pennsylvania, Phil Gutis saw a Facebook post about the announcement. “What the hell?” he wondered.
Before March, both had been enrolled in a clinical trial for an experimental Alzheimer’s therapy from the drug maker Biogen. When the studies were halted because the drug, aducanumab, did not appear to be working, they had been devastated.
On Tuesday, however, the company announced that a new data analysis showed the treatment reduced some patients’ decline; it said it would ask the Food and Drug Administration to approve the drug. Alerts about the news ricocheted around clinics, Wall Street, and the broader community of Alzheimer’s patients, caregivers, and researchers.
But just as with the cancellation of the trials, the resurrection of aducanumab was particularly jolting for the roughly 3,200 participants and their families:
“I don’t even know what to think.”
“It’s dizzying. Truly dizzying.”
“What does it mean to us now?”
Biogen’s reversal also restored a cautious sense of optimism that an effective Alzheimer’s treatment could be within reach. Some patients wondered if perhaps the experimental treatment they had been taking had actually been slowing the progression of their disease.
“I did feel like it was working,” said Debby Rosenkrantz, 66, of Cambridge, Mass.
For many, there was also the urgent question of what comes next. Patients wanted to know if they could start receiving aducanumab again, and when, and how. Even if the FDA were to approve the drug, the process could take a year. And then there would be a process of determining whether insurance companies would cover the therapy.
As Susan Woskie, Rosenkrantz’s wife, said, “This is precious time for folks with cognitive decline.”
In an interview with STAT, Samantha Budd Haeberlein, Biogen’s lead Alzheimer’s scientist, said the company was working to open a new study for former trial participants. The study will be open label, meaning there will be no placebo arm and all patients will get the treatment. She said patients should reach out to their trial sites so that they can start receiving the drug once regulators and review boards have given the study a green light.
Haeberlein said she did not want to put a timeline on how long that process might take, but that “we will work to get that study up and available for patients as soon as possible.” U.S. sites are expected to open before other locations because talks with regulators were already underway.
Some patients were already on the case. Gutis, 58, had emailed his trial site Tuesday morning and received a quick reply: “Holy smokes, big news!”
Gutis, who was diagnosed more than three years ago, said he had been feeling good lately, a fact he attributed to his increased exercise regimen. Now, though, he wonders whether he may be benefiting from a lasting effect of the drug. “In some ways, you want to stay positive, but it’s so disappointing that they yanked the trial and caused so much anguish back in March, when clearly they didn’t have all the data,” said Gutis, who described feeling a mix of frustration and elation.
Other patients echoed that sentiment. They were grappling with the cognitive function they had lost in just the last seven months, and feared it could not be recovered. At the same time, the mixed messages from Biogen were so confounding that some patients said that, as hopeful as they were, they couldn’t help but wonder if the company was trying to jam a drug through the regulatory process for financial gain.
Since the trial ended, many of the patients had been told whether they were in the treatment arm or the placebo arm. Families of some patients in the treatment arm said that the therapy seemed to be slowing the progression of the disease and that their conditions deteriorated faster when the monthly infusions were stopped. They knew that the apparent benefits seen in their family members did not prove the drug was effective overall, but the revival of the drug caused many to believe again that it was at least possible.
Deb, 61, who lives in Maine and asked that her last name not be used because her colleagues didn’t know she had Alzheimer’s, said she has had more trouble thinking clearly since the trial ended. “There’s just this void,” she said. “It feels like it goes on forever. And it scares me.”
And Borghoff, 55, of Forked River, N.J., said he thought he had become more easily agitated and anxious since March.
“I’m sort of scratching my head and jumping for joy at the same time,” he said about the Biogen decision. “I hope there’s not a lot of time wasted for us to get back on it,” he added.
Dick Carroll, 75, said his cognitive scores actually improved while he was on the trial. But the onetime teacher knew that those results might just have been him getting better at taking those tests, not a benefit of the drug.
Still, his outlook on Tuesday was one of pure optimism. He was looking forward to figuring out how to get back on the drug, even if it meant fighting through the Houston traffic to get to the trial site. “Some hope is better than no hope,” he said.
In North Carolina, Debbie Salerno, who heard the news from her mother-in-law over the phone — and who confirmed it herself after hanging up because she found it so surprising — was eager to learn more because her husband, Tony Milazzo, 56, had been in the trial. She said she felt his disease progression had taken off since the trial was halted, and he no longer wanted to socialize or engage with others as much.
She said that she had told Milazzo about the return of aducanumab but that she didn’t know how he felt. “He’s sitting right next to me, but his reactions don’t always come out in his expression,” she said by phone.
She then started addressing Milazzo. She told him the drug he had been on in the trial might be coming back, and asked how that made him feel.
“I would like to be on the medication,” he said.
“Do you think it was helpful?” Salerno asked.
“I don’t remember that part of it.”
“Does the thought of the medication that would be helpful to you, does that give you a little bit of hope?”
My husband was in week 164 and we have been told he received the high dose of the drug.
From the moment we were told the study was halted, i tried everything i could think of to get the continuation of this drug. My husband improved dramatically while on it, and in the 8 months off has steadily gone downhill. I spoke to the pharmacalogical division at biogen , begging for compassionate care or right to try. No one gave me a reason for the discontuation, but i told anyone who would listen that we would go to boston, testify before any fda committee, or subject ourselves to any scrutiny to reveal how much this drug improved both of our lives.
After all…would life be better with the results we obtained from the study, or would the dimuation of our lives off this drug be worth the possible side effects.
My only hope is that those of us enrolled in the study taking the full dose do not have to wait any longer to obtain this drug.
Please, please, let us try.
Simply betting on the new “business first” FDA course. As long as, a drug doesn’t obviously causes arm, it will be approved. Regardless whether it has any therapeutic value.
This is not a new course at the FDA; when I first started working in Pharma I helped write a few applications for new drugs. You simply had to prove the drug was safe. After that, whether it works or not was your nickel, at least in getting approved to run clinical trials. However, after that the FDA will not approve a drug unless it shows positive benefit. This was true then and is true now.
How is it possible, that even when billions of dollars were involved, the company, prematurely (without thoroughly analyzing the data) released a negative outcome for its pivotal trial. Or the game here was to release a negative result which would tank the shares. In turn, it would generate an opportunity for those involved to buy the shares at a low price point. Six months later suggest the drug works and share price go up. Sell the shares at a high point and make money. Hmmm
I work in basic pharma R&D, although not the clinical trial part, but it is really not possible to manipulate clinical trial data in the manner you suggest. For one the parsing of clinical trial data is checked by third-party independent contractors — indeed, the FDA essentially requires it. Secondly, there are way too many people involved, not only within the company, but outside consultants such as academic scientists. Any funny business would soon be spotted and most folks like myself who work at these companies would say something — if not directly, certainly would make sure any suspicions leak out. Few of us have a particular loyalty to any one company — most of us have worked in multiple companies and got into this business in the first place because we thought we could make a difference. There is no joy in seeing a bad drug get approved — in my case I would receive no financial benefit one way or the other.
The follow up analysis that showed positive results involved a larger number of patients. The effect may be borderline, but for some people it might be quite good. We’ll know more in the future. More importantly, it is a critical test of the idea that clearing beta-amyloid plaques from the brain improves cognition. That has only been a hypothesis so far. Even if the effect turns out to be marginal, this is very important to know, because it tells researchers what to focus on and paves the way for future drugs that will be more efficacious. For this reason alone, I hope it gets approved and used in the real world.
I suspect the bio-statisticians at FDA will want to know how they are controlling for Type I error in this post-hoc analysis. This may be enough to justify another study, but it probably doesn’t meet the standards of proof for NDA approval.
They could sue biogen for taking them off an active drug prior to biogen doing a full analysis of the data
Jimbo, this is how clinical trials work and whoever participates agrees to the regimen. The FDA is not real keen on extending clinical trials unless you show positive results, because after all why would you give a drug to someone that doesn’t seem to be working?
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