GAP President John Dwyer was quoted in NJ.com about the future of Alzheimer’s treatments if the CMS National Coverage Decision (NCD) proposal is approved.
Every day in this country, an estimated 1,000 people progress from moderate Alzheimer’s dementia to the final and most severe stage of the disease.
That’s a grim statistic in its own right.
But the gravity of it becomes even greater at a time when the federal government must decide whether it will give Alzheimer’s patients access to a controversial new drug that has the potential to slow the progression of their decline.
Should this new drug, Aduhelm, be covered by Medicare? Do we have — at long last — the breakthrough treatment for Alzheimer’s that we’ve been waiting more than two decades for? Or was its recent approval by the Food and Drug Administration a mistake, driven more by public pressure than by scientific proof?
The debate has become fierce, putting the nation’s leading Alzheimer’s experts at odds.
Dr. Dennis Selkoe, professor of neurology at Harvard, says evidence shows Aduhelm and three similar drugs still being studied “robustly clear” amyloid plaque from the brain, which he says is associated with the slowing of cognitive decline in typical Alzheimer’s patients.
Selkoe says this group of drugs is “the closest medicine has come to a disease-modifying approach” for Alzheimer’s dementia.
“That is why (Aduhelm) was given accelerated approval by the FDA based on its strong biomarker result and modest clinical benefit in some patients that should increase with time,” he says.
Dr. Brienne Miner, assistant professor of geriatric medicine at Yale, looks at the same evidence and comes to the opposite conclusion.
“I am deeply troubled by the pressure to use an unproven and potentially dangerous treatment in our patients, many of whom are desperate to try anything that might give them hope,” she says. “I am also saddened to think about the many other, much more beneficial ways we could use the resources that will be sucked up by (Aduhelm) to really help people and families with Alzheimer’s.”
In a lively discussion on the website AlzForum involving some of the country’s most renowned experts on the disease, opinion is running about two to one in favor of a proposal that would tightly limit Medicare coverage for Aduhelm. Many of the quotations in this column come from that forum or from expert opinion posted on the Medicare site.
As a journalist who writes a column about brain health and dementia, I understand the widespread skepticism this drug has engendered. But as the cacophony of criticism gets louder, I hope it does not drown out other voices that also need to be heard.
I’m talking about the voices of respected neurologists who have tested this drug in clinical trials and say they’ve seen patients benefit from it.
And above all, I’m talking about those who have the most at stake here: the 6.2 million people in this country who have Alzheimer’s and the family members who care for them.
I’m talking about people like Jeff Borghoff, a 57-year-old Alzheimer’s patient in South Jersey who has been taking Aduhelm for several years through a clinical trial.
Last summer, he told me he’s convinced the drug helped significantly slow the progression of his dementia.
“For myself and my family, it’s been a success,” Borghoff said. “It’s been five years, and I think statistically speaking when a person is diagnosed with Alzheimer’s at my age, the trajectory (of decline) is rather quick. But I still function cognitively very well. Some of my (test) scores have increased over the years.”
Borghoff was among the many people whose hopes were crushed when drugmaker Biogen declared in March 2019 that it was shutting down further research on Aduhelm because results showed it to be ineffective. But a stunning reversal came six months later. Biogen announced that after further review of the study data, it found a small group of patients who received a higher dose toward the end of the clinical trial who seemed to benefit.
Based on that, Biogen took Aduhelm to the FDA and received conditional approval for patients with mild cognitive impairment or early stage Alzheimer’s. The authorization was based on evidence it reduced beta amyloid plaque in the brain, which the FDA deemed “reasonably likely” to slow the progression of the disease.
That decision has been pilloried ever since, and one brouhaha has led to another. Now that the drug is FDA-approved, the next controversy becomes: Should it be covered by Medicare?
That question has huge implications.
An estimated 1 million Alzheimer’s patients could be eligible to get this drug under Medicare if it’s covered and if their doctors are willing to prescribe it to them.
Usually, Medicare coverage of an FDA-endorsed drug is nearly automatic. But the Centers for Medicare and Medicaid Services (CMS), which decides what does and doesn’t get covered, is balking at this one.
Last month, CMS issued a draft policy that would cover Aduhelm (and other drugs like it) only for Alzheimer’s patients who are participating in approved clinical trials. It’s essentially insisting on a lengthy period of additional, highly regulated testing of the drug, with a promise of broader coverage for Medicare recipients if further study establishes that Aduhelm is safe and effective.
The Medicare system is accepting public comment on the plan through Feb. 11, and its final decision is due April 11.
The proposed policy has received a far more favorable response in both medical and political circles than the FDA approval did.
“The CMS did the right thing,” says Dr. Jason Karlawish, co-director of the Penn Memory Center in Philadelphia. “The magnitude of Aduhelm’s costs and harms and uncertainties are stunning. Its lackluster reception at major medical centers, insurers, European and Japanese drug regulators all show the data are not compelling. This isn’t the drug to take a financial gamble on.”
U.S. Rep. Frank Pallone (D-6th Dist), chair of the House committee on Energy and Commerce, issued a joint statement with Rep. Carolyn Maloney (D-N.Y.) in which he commended CMS for “striking a balance between the need for Alzheimer’s patients to access treatment with the need to gather more evidence on the treatment’s safety and efficacy through clinical trials.”
But this is a time when dissenting voices also need to be considered, including those who believe Medicare seems to be applying a different standard to this drug than it has in the past for medications that received accelerated approval for other diseases, including cancer, HIV and multiple sclerosis.
John Dwyer, president of the Global Alzheimer’s Platform Foundation, told NJ Advance Media that if the CMS policy is approved as written, fewer than 1% of the people who might benefit from Aduhelm or similar drugs would have access.
“Why are Alzheimer’s patients being subjected to an unprecedented, onerous process?” Dwyer asks. “It puts millions of Alzheimer’s patients at risk of never being able to benefit from this class of drugs. … Why are we getting treated so differently?”
Critics contend that the draft policy makes the drug available to people who are affluent enough to afford it or who have access to better health care and can enroll in a clinical trial, while denying the drug to the disadvantaged.
That’s particularly of concern due to the high cost of the drug. Even its most ardent supporters were shocked when Biogen announced Aduhelm’s annual price tag would be $56,000. Although the drugmaker has since reduced the cost to $28,000 a year, it remains out of reach for most Americans. And so far, most insurers are declining to cover it, leaving Medicare as a last resort for many patients hoping to receive Aduhelm.
“For Aduhelm, it seems the CMS is creating more inequality rather than solving it,” says Dr. Philip Scheltens of the Alzheimer Center Amsterdam. “The drug is on the market, and those who can afford it can be treated, while those who cannot afford it have to be put into a clinical trial with a 50% chance of receiving a placebo.”
Critics of the CMS plan also argue that decisions about the safety and effectiveness of the drug can best be made by doctors and their patients.
“Aduhelm was approved under accelerated conditions to allow patient access to treatment while additional data are gathered. This is how it is done with cancer therapeutics and how it should have been done here,” says Dr. Jeffrey Cummings, director of the Center for Transformative Neuroscience at UNLV. “This decision deprives patients with early Alzheimer’s of the opportunity to engage in informed discussions about whether the benefit/harm balance makes Aduhelm the right choice for them.”
Are doctors and patients capable of making such decisions wisely when it comes to Alzheimer’s treatment? I have news for you. They’re already doing it every day.
Prior to Aduhelm, there was no FDA-approved drug for people with mild cognitive impairment (MCI) that had not yet progressed to dementia. But there are Alzheimer’s drugs approved by the FDA, and doctors have the latitude to prescribe them “off-label” to people with MCI.
These drugs don’t slow the progression of Alzheimer’s, but they do ease some of its symptoms for a while. There’s no definitive proof that these drugs benefit patients at the MCI stage. But there’s evidence they benefit some people, and doctors are given the discretion to prescribe these drugs as long as the patients know the benefit is not fully proven and as long as they can tolerate the side effects, which can be severe for some people.
This “off-label’’ prescribing is not controversial or underhanded. It’s standard medical practice that entrusts the physician and patient to come to the best decision together on whether an approved drug is appropriate for that particular person.
So if the current Medicare policy is enacted, it will create the ultimate dichotomy. Doctors will continue to be able to give patients with mild cognitive impairment any one of several Alzheimer’s drugs that are not approved by the FDA for MCI and that we know for sure don’t slow the progress of the disease, but their hands will be tied on Aduhelm. And their MCI patients will not be able to obtain the only Alzheimer’s drug actually approved by the FDA for mild cognitive impairment and that may slow the progression of the disease.
That is a cruel irony to ask Alzheimer’s patients to accept. But given the stampede of support that is building around the proposed Medicare policy, they may have to accept it.
If so, then there are two other elements of the draft policy that beg to be revised while it’s still under review.
The first is the prolonged period of additional research that it imposes on Aduhelm and other drugs like it. The research regimen outlined in the draft policy could take seven to 10 years to carry out, according to estimates by The GAP Foundation and UsAgainstAlzheimer’s. That means even if Aduhelm proves effective in delaying cognitive decline, it might not become eligible for broad Medicare coverage until 2032.
To be clear, we need further research on Aduhelm. Absolutely. But not at the plodding pace that Alzheimer’s research has traditionally taken. We need science, and we need rigor. We don’t need languor. We have got to move faster.
And that’s the welcome direction that Alzheimer’s drug discovery has taken in recent years. The emphasis of the GAP Foundation and others has been on identifying better drugs to test and designing clinical trials that are more efficient, less costly, and most of all, result in a finding ASAP.
The accelerated process that was used in the FDA approval of Aduhelm is an example of that effort to speed up research and the availability of promising drugs. You may agree with the FDA’s decision or you may disagree, but we can all agree that a far greater sense of urgency and innovation is needed in the search for a cure.
The Medicare policy must be extra careful not to stifle that, and encourage an approach along the lines called for by Maria Glymour, an associate professor at the University of California San Francisco.
“I hope we as an Alzheimer’s research community can band together to ensure rapid fielding of large, inclusive randomized trials,” Glymour says. “I advocate for pragmatic trial designs because I believe they will enable faster progress with more diverse participant bases.”
The other element of the draft policy that seems misguided is the decision to have it cover an entire class of drugs, and not just Aduhelm, the therapy it is clearly aimed at.
As written, the policy applies to all drugs known as “anti-amyloid monoclonal antibodies,” designed to combat Alzheimer’s by clearing away the beta-amyloid plaque that is one of the hallmarks of the disease.
If Medicare insists on throttling Aduhelm, that is its prerogative. But to apply this to an entire class of drugs is short-sighted and a disservice to Alzheimer’s patients.
Right now, three other drugs of this type are in the pipeline, and that includes two that could come before the FDA for approval within the next 18 months. Based on early indications, these drugs look promising. Yet if one or more of these up-and-coming drugs turns out to be more effective, safer and cheaper than Aduhelm, it would be held hostage by the same restrictions targeted for Aduhelm — meaning an extended wait before it becomes eligible to be covered by Medicare.
“Drugs that are currently almost ready for FDA approval are going to be similarly quarantined and thrown into this gauntlet after FDA approval,” Dwyer says. “It’s unimaginable.”
It’s one thing to delay Medicare coverage for a single medication with questionable evidence. But if a better drug comes along in 2023 or 2024, and the evidence of its benefits and safety clearly warrants FDA approval, Alzheimer’s patients deserve to have access right away, not in some distant future preordained by Medicare’s decision to lump it in with Aduhelm.
That is my opinion. But here’s what matters more: What is your opinion? The Centers for Medicare and Medicaid Services will be taking comments from the public through Feb. 11. You can learn more about the proposed policy or post a comment here. If you want to read comments that already have been posted, go here.
Tony Dearing may be reached at email@example.com. Follow him on Twitter @TonyDearing. Find NJ.com on Facebook.
Originally posted by NJ.com on February 3, 2022.