NEW YORK – Newly approved anti-amyloid therapies have spurred hope for patients and caregivers affected by Alzheimer's disease, but access to these drugs could be stymied by a lack of convenient and available beta-amyloid testing options.
The US Food and Drug Administration's approvals of Leqembi (lecanemab) this year and Aduhelm (aducanumab) in 2021, while controversial, opened new treatment options for Alzheimer's patients.
Both drugs are disease-modifying therapies developed by Biogen and Eisai and received accelerated approval from the FDA based on their ability to clear beta-amyloid, a hallmark sign of Alzheimer's that many say is the root cause of the progressive neurodegenerative disease. Eisai has since submitted a supplemental biologics license application seeking traditional approval for Leqembi, for which the company will have to prove the drug not only reduces beta-amyloid but also results in actual clinical benefits. Meanwhile, Aduhelm is on the market, but Biogen is no longer marketing it as the company shifts its focus to Leqembi.
These two approvals have paved the way for other amyloid-clearing Alzheimer's drugs. For example, Eli Lilly has said it plans to seek traditional approval this year for its drug donanemab.
The availability of such drugs "does, obviously, pick up the need to detect amyloid," said Sanford Auerbach, a neurologist at Boston Medical Center and an associate professor of neurology at Boston University's Chobanian & Avedisian School of Medicine. According to the FDA's labeling, both Leqembi and Aduhelm are only indicated for patients with early-stage Alzheimer's and with confirmed presence of amyloid pathology, although the agency doesn't specify a testing method to detect it.
Auerbach, while convinced that beta-amyloid testing use will increase in the wake of Leqembi's approval, said he's not sure how markedly the demand will rise. There are open questions around the clinical benefits of anti-amyloid drugs on the market today, which might discourage doctors from prescribing them, he said.
It's also unknown to what extent additional testing is needed after administrating Leqembi to monitor amyloid clearance.
Prior to the FDA's approval of these drugs, beta-amyloid testing was mostly done to aid in the diagnosis of atypical cases, for example, if a young patient presented with Alzheimer's symptoms or if testing was needed as part of a clinical trial. Since Alzheimer's drugs used thus far have focused on improving disease symptoms, knowing whether patients had amyloid pathology in the brain wasn't needed for treatment.
There are two main options for gauging beta-amyloid in patients today: test for it in their cerebrospinal fluid (CSF) or conduct a PET scan with a radiotracer.
Both approaches have drawbacks depending on patients' priorities. CSF analysis requires patients to undergo a lumbar puncture that, while minimally invasive, some are hesitant to receive, Auerbach said. PET scans, on the other hand, come with logistical and financial barriers. Not everyone lives near a healthcare facility that has PET scan equipment to test for beta-amyloid, nor will all facilities staff specialists trained on how to read results.
And PET scans can be expensive, running at about $3,500 per scan, said Jeffrey Cummings, director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas. "That's a lot of money," he said.
Neither PET scans nor CSF beta-amyloid tests are typically reimbursed by Medicare, with such PET imaging covered only when performed within certain studies and limited to only one scan per Medicare patient across their lifetime. The Centers for Medicare & Medicaid Services does not have a national coverage policy for CSF beta-amyloid tests, leaving decisions to local Medicare Administrative Contractors.
That's just for the tests themselves. Leqembi, with a list price of $26,500 annually, and Aduhelm, at roughly $28,000 annually, with a lower cost the first year of treatment, aren't always covered by commercial insurers, either. And CMS currently only covers anti-amyloid drugs when Medicare patients receive them in clinical trials and covers related services, such as PET scans, if required by the study protocol.
Ultimately, the availability of Leqembi and Aduhelm will only boost demand for beta-amyloid testing if insurers start covering the drugs more, said Douglas Scharre, a neurologist and director of the division of cognitive neurology at the Ohio State University Wexner Medical Center. "Medicare and other insurers are not paying for these drugs, and they're generally too costly for most individuals to afford," he said. Without access to the drug, there's no reason to test. "It all is really going to come down to whether they will be paid for," he said.
CMS earlier this month said it plans to cover anti-amyloid Alzheimer's drugs, with certain data collection requirements, if they receive the FDA's traditional approval. The therapies, which are currently approved under the accelerated approval pathway based on beta-amyloid clearance as a surrogate endpoint, must instead have been confirmed to improve patients' cognitive functions.
The FDA is expected to decide whether to convert Leqembi's accelerated approval into a traditional approval based on confirmatory data by July 6. Industry observers expect the agency to approve the drug under the traditional pathway, since an FDA advisory committee recently agreed that data submitted by Eisai and Biogen confirmed that Leqembi slows disease progression, despite some healthcare groups' view that the treatment has a modest treatment benefit.
Meanwhile, CMS, in its recent announcement about expanding coverage for anti-amyloid treatments that garner full FDA approval, did not address Medicare coverage for diagnostic tests to determine whether or not patients have beta-amyloid, drawing ire from industry groups like the Medical Imaging & Technology Alliance, which argue that lack of coverage for amyloid testing services will hinder access to the therapies.
Other tests on the market, none of which are yet approved by the FDA, analyze plasma for signs of beta-amyloid and other markers of disease. Several companies like Quest Diagnostics and C2N Diagnostics sell laboratory-developed tests for this purpose, and earlier this year, pharmaceutical giants Eli Lilly and Roche announced they would work together to advance a blood-based test for beta-amyloid.
Today, such tests tend to be used to screen patients before they commit to an amyloid PET scan. In Eisai's AHEAD study, in which investigators are assessing whether Leqembi can delay or prevent cognitive decline in those who are asymptomatic but have elevated levels of beta-amyloid, interested patients are screened using C2N's PrecivityAD blood-based test, and positive results are confirmed with an amyloid PET scan. That has cut down the number of expensive PET scans that would be necessary to screen out patients without beta-amyloid, said Michael Irizarry, Eisai's deputy chief clinical officer of Alzheimer’s disease and brain health.
Blood-based diagnostics will be a "game changer," agreed Biogen President and CEO Christopher Viehbacher, on a Q4 earnings call with market analysts in February. However, Viehbacher expects this to take a couple of years. "If we can eliminate the PET scan … or the lumbar puncture, this will make it a whole lot easier for the whole medical community to at least get the diagnosis," he said. "And we can probably reduce the overall treatment cost of a patient."
Availability of blood-based tests might end up being the greatest driver of amyloid testing adoption, experts said. Not only will patients likely prefer to have a simple blood test, but primary care doctors can also easily order a blood test and, based on the results, refer patients to a specialist — rather than patients needing to see specialists to get tested in the first place.
"Everybody would rather have a relatively cheap blood test than an expensive PET scan, and they'd rather have a blood test than a spinal tap," Cummings said. Once such tests gain regulatory approval, "it's going to have an enormous impact."