Whether the first U.S. drug intended to thwart Alzheimer’s disease signals a major milestone or “dangerous hope” depends on which Western Pennsylvania doctor you ask.
One thing many in the medical community seem to agree on: They didn’t expect the drug to win over federal regulators, at least not yet.
The Food Drug and Administration made history this month by approving Biogen’s aducanumab, under the label Aduhelm — the first Alzheimer’s disease drug to be available in decades and the only one that cites a goal of slowing cognitive decline (as opposed to merely addressing the disease’s progressively worsening symptoms). The move spurred celebration by the likes of Alzheimer’s Association advocates, families and caregivers across the country.
Physicians throughout Western Pennsylvania and nationwide remain mixed on whether they plan to prescribe Aduhelm, if and when it becomes an affordable option for their patients. Three FDA committee members resigned in the days following the greenlighting of the drug, which an FDA advisory committee voted against in November.
“We’re getting tons of calls trying to explain this,” said Elisa Poggi, director of Insight Clinical Trials in Beachwood, Ohio, where seven Alzheimer’s and mild cognitive impairment-related clinical trials are in the works. “They’re making it out to be the best thing since sliced bread, and it isn’t. … It’s disappointing. I’m very surprised.”
Biogen’s market potential for Aduhelm looms large: More than 6 million Americans are living with Alzheimer’s disease — a figure some experts say could double by 2050. In Pennsylvania, state officials estimate more than 320,000 people will be living with the disease by 2025.
Critics are voicing concern that because of such high demand for any treatment, too much money and attention could get devoted to a drug that might not do what it’s supposed to, based on a dearth of appropriate analysis and convincing results. Only one of two Biogen’s Phase 3 human clinical trials of Aduhelm achieved statistically significant results. Aduhelm aims to slow the progression of Alzheimer’s disease by removing amyloid protein plaque buildup in the brain. Even if the plaque-reducing is successful, the amyloid-removal approach hasn’t been proven to be a significant solution to curing or slowing the broader disease based on decades of failed trials, though it may be one piece to the larger puzzle, several experts told the Trib.
“We all know that it will disrupt resources for future studies,” said Dr. Steven DeKosky, deputy director at the University of Florida’s McKnight Brain Institute, a member of Biogen’s drug monitoring committee for Aduhelm and former director of Pitt’s Alzheimer’s Disease Research Center. “Of course, we’d like the first drug that comes out to be the superstar drug. It doesn’t always happen that way.”
It’s unclear what restrictions insurance companies could place on related testing and patient eligibility for the drug, such as limiting it to patients in certain stages of the progressive disorder, which on average leads to death in three to 11 years. It’s also unknown how much the drug will cost for the average patient, with Biogen pegging annual treatments at $56,000 plus costs for related testing.
In a statement issued to the Trib, a spokesperson for the Centers for Medicare & Medicaid Services said that the “milestone provides hope to families, caregivers and the older Americans living with Alzheimer’s who rely on Medicare for health coverage.
“CMS is reviewing the FDA’s decision regarding aducanumab and will have more information soon,” the agency’s spokesperson said by email.
A small number of people who take the drug will be monitored via a Phase 4 clinical trial, a condition of the FDA’s approval. The agency could yank the drug at any time if deemed unsafe or repeatedly ineffective.
“The FDA will not approve a medication unless they believe that the risk-benefit ratio is in favor of benefit,” DeKosky said.
The Tribune-Review spoke to three Western Pennsylvania doctors who specialize in neurology. Here are their takes on the newly approved Alzheimer’s drug, Aduhelm:
Dr. Arvind Vasudevan, neurologist at Excela Health Westmoreland Hospital in Greensburg
“In a year, maybe I’ll be eating crow, but I think it’s worse than false hope. It’s dangerous hope. … A lot of my colleagues feel the same way.
“There was such a drive to put this drug out because there hasn’t been a treatment for Alzheimer’s, but in the process they really didn’t finish the data and analysis. …
The same doctors who were looking at the imaging, they were also doing the clinical rating scales on these patients, and these scales are somewhat subjective. It just adds too much bias to make me comfortable. Were they truly blinded? I don’t think they were; a third of their patients had imaging abnormalities consistent with taking the drug. It’s not randomized control, and it’s definitely not blinded.
“You have this drug where we’re not absolutely 100% sure it’s safe — we assume it is, but we know that a third of (those who take it) developed brain abnormalities on their MRIs, and they haven’t really followed the patients for a long period of time. … I’m always a little concerned aboout swelling in the brain as well as blood in the brain.
“And what is going to end up happening is that all of these other newer treatments that may not have to do with amyloid (protein) may get put on the sidelines, as will the other pharmaceutical companies are going to try to quickly get out the the next amyloid drug — and I think it’s a big problem. None of them (amyloid-related experimental drugs thus far) work. They haven’t been working.
“The efficacy, from my standpoint, hasn’t really been proven. So you have a drug where you may have a lot of minuses and no pluses.
“If CMS decides to honor this, it’s going to be brutal. The cost to the taxpayer is going to go up tremendously.”
Will you prescribe it?
Vasudevan: “No. I’m not going to recommend it. If a patient still wants to take it (after discussing my concerns), I will refer them to someone else.”
‘One step forward’
Dr. Oscar Lopez, director of University of Pittsburgh Alzheimer’s Disease Research Center at UPMC Montefiore in Pittsburgh
“So you have skepticism in the scientific area, and you have a great deal of enthusiasm in the families.
“The thing is that, since 2003, we haven’t seen any drug approved. And all the big trials, very expensive trials, were negative. So this is the one that at least one of the two trials was positive. … It gave us some hope. We have at least a disease-modifying drug in the market for a viable treatment for people with the disease.
“If you look at this through a positive lens, this is going to encourage innovation. And, most likely, it’s going to attract more people to develop more compounds, and in the near future we’ll have much better medications.
“There can be adverse effects — for example, the Biogen drug can cause microhemorrhages in the brain. Up to 40% of people had those small hemorrhages with practically no symptoms. That’s why the FDA required for people getting this treatment to have an MRI of the brain every six months.
“I see this as one step forward in our fight against this disease. There will be more drugs coming up in the future; there are many compounds in the piepline. But at least now, the patients have something.”
Will you prescribe it?
Lopez: “Yes. If the patients want to have the medication, we will prescribe it.”
Dr. Eric Weisman, director of Memory Disorders Clinic for Allegheny Health Network Neuroscience Institute at West Penn Hospital in Pittsburgh
“We’re excited about this at Allegheny Health Network. There will be 600 centers worldwide that will be able to offer aducanumab … We’ve been involved with Biogen for more than nine months and are getting ready to treat people with our first drug.
For instance last Tuesday, we had eight new dementia patients, mild cognitive impairment patients, and about half of them right at the beginning of the visit were asking about aducanumab — and it had just been approved the day before. They had heard about it.
“We give them lots of options and alternative therapies that are available now and what looks like will be coming down the road in the future. For aducenumab, we tell them that we have a modern infusion center in the Mellon Pavilion where my main office is at West Penn, and we tell them that the medication has to be given by infusion once a month.
“I’ll be frank: It got approved faster than I thought it would. I thought we had a little bit more time to get ready for this. We’re having to hire more doctors and more support staff. … And just because this medication is FDA-approved, is Medicare going to pay for it?
“There was a lot of pressure to bear on not only the FDA but the advisory committee to go ahead, because it’s been 30 years since we started looking for a treatment, and we haven’t had anything that modified the disease. This is the first medication.
“So maybe our treatment for Alzheimer’s disease is going to be an amyloid drug, two different types of tau (protein-targeted) drugs, and then something for supporting synapses downstream and neuroinflammation.
”It might be a five drug cocktail like with AIDS, and then as we get better at doing it, a single pill.”
Will you prescribe it?
Weisman: “We have about 100 people who are being worked up for qualifying to receive it right now.
“We want to stick to the protocol that was used in the research studies (including patients in early Alzheimer’s disease stages), and may be even more selective than that. We don’t want to give the medication to someone who is on a blood thinner, for instance. … The people we are going to be treating are people we are pretty sure are going to not only test positive for amyloid but not have a lot of vascular diseases, and not have medical problems that would make them less-than-ideal candidates, at least to begin with. … Somebody who’s not going toalso do the lifestyle changes might not be a good candidate to invest in a newer therapy like this. Maybe the second 100 patients that get treated, we might start expanding.
“I don’t know what percentage of people who want to be treated will be treated, but it will be a fraction, and it will be based upon real sound judgment and understanding that there are other therapies available.”
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Natasha Lindstrom is a Tribune-Review staff writer. You can contact Natasha at 412-380-8514, email@example.com or via Twitter .