Thyroid medication has helped Bob Wiltshire since he was in his late teens.
A hormone suppressant has kept him alive since he was diagnosed with prostate cancer almost three years ago.
He would like to believe a new immunotherapy drug approved this week by the FDA might one day stave off the Alzheimer’s disease he learned he had in early 2019, but is skeptical.
“There’s nothing definite that it's going to cure anything,” said Wiltshire, 79, a retired salesman who lives in Eden.
Alzheimer’s, a degenerative and fatal brain disease, is the most common form of dementia worldwide. It accounts for roughly two of every three dementia cases globally.
Medications that somewhat slow progression of the degenerative, fatal condition have been available for more than two decades but aducanumab is the first FDA-approved drug proven to destroy amyloid plaque buildup in the brain, a telltale sign of Alzheimer’s.
In some cases, it may reverse the course of the disease.
A $1 billion plant in Switzerland is ready to produce the drug for the American marketplace but questions about its risks, cost and benefits have complicated the rollout.
“We all want a disease modifying agent but in the absence of a home run, we need to proceed with caution,” said Dr. Bruce Troen, a geriatrician and director of the University at Buffalo Center for Successful Aging. “This therapy is not a home run.”
Aducanumab could be available in the region before the end of the month.
Representatives with Boston-based international drugmaker Biogen are scheduled to meet next week with specialists at Dent Neurologic Institute and the University at Buffalo Alzheimer‘s Disease and Memory Disorders Center, which spearhead dementia treatment in Western New York.
Leaders with both helped answer key questions about the medication.
Q: What is aducanumab (brand name Aduhelm)?
It is a monoclonal antibody that takes about an hour to infuse into the bloodstream and stir the immune system to attack and destroy an amyloid protein believed to influence the start and progression of Alzheimer’s disease. The medication targets the protein in a similar way as monoclonal antibodies zero in on the spike protein that helps the new coronavirus proliferate.
Cognitive decline is slower for patients prescribed these drugs because they block an enzyme that disrupts important neuron communications in the brain. They have not shown the ability to stop or reverse damage already caused.
The FDA conditionally decided that aducanumab might yield that power.
“In almost 20 years, we haven't had any new medication that we would offer in Alzheimer's disease,” said Dr. Bela Ajtai, a neurologist who directs the Dent Integrative Center for Memory. “This is the very first one that would try to work on the actual pathology in the brain and not just with the symptoms.”
Q: Who would make a good candidate to receive a drug like this?
Those like Wiltshire. His wife, Sandra, started to handle outings a year before his diagnosis because he kept scheduling conflicting plans. He also began to misplace things. Six months ago, he stopped driving at the urging of health specialists.
“I've come to the agreement, and the understanding, that Sandra’s more in tune with things that are going on here, and we work together to make things happen,” he said.
Dent Neurologic and other specialists helped diagnose Wiltshire early, which is critical so those with Alzheimer’s and their caregivers can devise a holistic care plan and better address the damage the condition already has caused, said Sarah Harlock, program director with the Dent memory center.
Q: Why is there is disagreement about aducanumab effectiveness?
Middle and late-stage trials showed the drug can clear amyloid plaque from the brain, but it has yet to show a clear clinical benefit, said Dr. Kinga Szigeti, director of the UB Alzheimer‘s Disease and Memory Disorders Center.
It also remains unclear what role amyloid plays in the development and progression of Alzheimer’s disease, or what impact reducing or removing it will have.
“This is a complicated disease that affects the brain and millions of cells in the brain,” said Szigeti, also a neurology professor at the UB Jacobs School of Medicine and Biomedical Sciences. “Treating it is like turning a huge battleship. You can clean out my brain but if I keep going down with Alzheimer's, I really don't care.”
The FDA gave conditional approval by reasoning that the Biogen therapy has shown at least some therapeutic advantage. Nearly two dozen similar drugs have failed in clinical trials.
Patients who choose the treatment will in essence become part an ongoing process to see if aducanumab provides meaningful results. If it becomes clear the drug is no help, or too risky, the FDA can rescind its approval.
This week’s federal approval sparked controversy because it came after a medical advisory panel last November overwhelmingly recommended against it. Three FDA members who opposed it wrote in a recent JAMA commentary that the government agency’s “unusual degree of collaboration” with Biogen “potentially compromised the FDA’s objectivity” and cast doubt on revised data showing better results than initially reported in one of two Phase 3 clinical trials. Both trials at first showed no benefit.
The Alzheimer's Association has supported the drug throughout its development and touted the revised data that showed a 22% reduction in cognitive and functional decline in one of the two studies as good reason to move forward.
"History has shown us that approvals of the first drug in a new category invigorates the field, increases investments in new treatments, and encourages greater innovation,” said Maria C. Carrillo, chief science officer with the nonprofit. “We are hopeful that this is the beginning – both for this drug and for better treatments for Alzheimer's."
Q: What sort of impact might it have?
Once conditional approval results are clear, treating physicians and Biogen will know if the drug works, which types of Alzheimer’s patients benefit most and whether the treatment is worth the risks. Ajtai said clinicians should have a reasonable idea within a year.
Clinicians also will monitor risks. More than one-third of patients in one of the trials experienced brain swelling and nearly 20% had brain bleeding, though symptoms generally were mild and controllable.
Q: How much will the therapy cost?
Biogen will set the cost at up to $56,000 a year. Effectiveness and risks also will need to be monitored through expensive diagnostic PET scans and MRI tests.
The regional center is one of 10 Centers of Excellence for Alzheimer’s Disease that were established last year as part of a five-year, $26.5 million effort statewide.
A big signal that the drug shows a clinical benefit will be if health insurers pay for all or most of the cost – which would hold “humongous implications for American health care,” Szigeti said. If so, insurers and taxpayers could be on the hook for treating up to 2 million eligible patients a year.
The Centers for Medicare & Medicaid Services will set the standard for what most private insurers do.
Amber Hartmann, speaking for Highmark BlueCross BlueShield of Western New York, and Martin Burruano, vice president for pharmacy with Independent Health, said the two largest regional insurers will use an evidence-based drug evaluation process that will take months.
Q: Are there other treatments or therapies on the horizon?
Ajtai considers the drug the first in a series of trials that will provide disease modifying benefits this decade. In fact, Biogen and fellow pharmaceutical giant Eli Lilly have been in an intense competition to bring their similar therapies to market.
The UB memory center participated in the multicenter Eli Lilly trial of donanemab (the “mab” stands for monoclonal antibody).
“The exciting part is that there's so much work, so much enthusiasm, so much organized collaboration is going into Alzheimer’s research,” Szigeti said. “But which drug is going to pan out as the one that cures the disease, or really makes a significant halt on the progression? It's unpredictable at this point.”
Q: Where can those impacted by Alzheimer’s find out more?
The regional Chapter of the Alzheimer’s Association encourages people who want to learn more about this treatment for themselves or a loved one to talk with their health care providers and visit alz.org/wny.
Szigeti discusses with patients the risks and costs of taking an unproven drug. She also talks about the often-slow progression of the disease, importance of an early diagnosis and other ways to delay its onslaught while aducanumab and other drugs come into the health care marketplace.
Most will be able to sit tight for six months to a year as the situation clarifies, she said, though she knows others will see the newly approved monoclonal antibody as a first, best hope to turn back Alzheimer’s.
This is why she will meet with Biogen on Tuesday so the UB Alzheimer’s center can offer aducanumab in its infusion center when it becomes available. It is why Dent Neurologic specialists will do the same on Monday, have started a waiting list and gauged interest on its website, dentinstitute.com.
Dent already has reached out to regional insurers to discuss reimbursements and learned from Biogen that the drugmaker will offer special programs to help offset out-of-pocket costs for some patients, said Christine Mann, chief operating officer and director of infusion operations.
“We are going to participate in this study,” Szigeti said, “because I want to know if this drug works or doesn’t work ... but I’m not going to push anybody to sell their house to get a drug that’s not been proven to work.”
Bob Wiltshire is among those who will wait and see.
Despite his slow decline, he and his wife said two medications, Namenda and Aricept, keep the most debilitating Alzheimer’s symptoms largely at bay, at least for now. Each comes with a $15 monthly copay. Healthy eating and exercise, and support through the regional Alzheimer’s Association chapter also help.
“It's kind of hard to be hopeful because you just don't know what the future holds, and with these mixed reviews … ” said Sandra Wiltshire, her voice trailing off.
Her husband chooses to look on the bright side.
“Somebody's going to come up with something better,” he said, “and it won't be long.”