By Kerry Dooley Young and Liz Seegert
If you are going to cover the debate about the Medicare decision to limit payment for Biogen’s Aduhelm drug for Alzheimer’s disease, it’s critical to understand a major disagreement between two federal agencies.
Last year, The Food and Drug Administration (FDA) granted accelerated approval to Aduhelm, betting heavily on the potential of drugs that clear amyloid plaque in the brain. In April 2022, The Centers for Medicare and Medicaid Services (CMS) signaled greater skepticism about this approach.
We offer three tips below for reporting on Medicare’s coverage decision on Audhelm.
- Dig into the CMS decision memo of Medicare’s Aduhelm payment policy.
- Make clear the uncertainty surrounding current evidence for — and against — Aduhelm.
- Consider adding details on what research to date shows ways people can lower their risk for Alzheimer’s disease or better cope with this condition.
First, here is some background material.
The FDA’s 2021 decision to approve Aduhelm was a highly controversial move, as earlier reported by AHCJ. There’s been a considerable debate since about whether the agency made the right call, as well summarized in this New England Journal of Medicine article, “Revisiting FDA Approval of Aducanumab.”
In simple terms, you can say that FDA officials opted to allow patients prompt access to amyloid-reducing drugs while companies continue studies meant to prove this approach works. Genentech and Eli Lilly also have drugs similar to Aduhelm in clinical trials. These are all bioengineered antibodies designed to teach the immune system to recognize amyloid as a threat.
CMS made a decision that will at least temporarily limit federal payments for Aduhelm to cases where patients are enrolled in certain clinical trials. The Medicare program also intends to place restrictions on future coverage of drugs similar to Aduhelm if they reach the U.S. market.
In a memo explaining the decision, CMS officials said there is not yet a “convincing evidentiary link between clearance of amyloid and meaningful clinical benefit (an improved health outcome).” That view is based on CMS’ review of the history of failures and setbacks seen to date with research on amyloid-targeting drugs in Alzheimer’s disease, including Aduhelm studies.
In writing on this topic, it’s also worth noting that FDA is not challenging CMS’ right to take a different stance on Audhelm.
On April 8, FDA Commissioner Robert Califf, M.D., issued a joint statement with CMS Administrator Chiquita Brooks-LaSure following the coverage decision.
“Underpinning both of our agencies’ work is the unwavering commitment to use reliable data to ensure that effective treatments are made available to patients,” they said. “CMS can conduct its own independent review to determine whether an item or service should be covered nationally by Medicare, including examining whether it is reasonable and necessary for use in the Medicare population.”
Tips for covering Medicare’s Aduhelm decision
1. Dig into the CMS decision memo of Medicare’s Aduhelm payment policy.
Although a bit wonky, the CMS memo is richly detailed and clearly written. Reading the memo may present new angles of interest.
In the memo, CMS officials summarized the objections raised to a draft proposal the agency earlier released on its payment plans for Aduhelm and similar drugs. The CMS officials then provided the agency’s response to these concerns.
People questioned, for example, why CMS balked at broadly covering Aduhelm when Medicare already pays for cancer drugs cleared with accelerated approvals. (An accelerated approval is a conditional clearance that allows patients access to medicines, while companies continue research to prove their drugs provide the expected benefit.)
In responding to this question about accelerated approvals, CMS officials sought to draw a clear distinction between what’s known about cancer drugs and what’s still unclear about attempts to treat Alzheimer’s disease.
The FDA will consider data on biomarkers or surrogate endpoints for accelerated approvals. For cancer, a widely accepted surrogate endpoint is evidence of delay in tumor growth seen in an early-stage test of an experimental oncology drug. The delayed tumor growth is considered likely to predict the drug will in further testing prove successful in extending the lives of cancer patients.
There’s “scientific evidence on and clinical expert acceptance of the association between progression-free survival and overall survival for cancer drugs,” CMS staff wrote in the memo.
But that’s not the case when amyloid is used as a surrogate marker for Alzheimer’s disease, CMS said. There is not yet “evidence that reducing beta-amyloid plaque in the brain will reduce the effects of Alzheimer’s disease by slowing down or maintaining cognition or function or improve survival,” CMS wrote.
2. Make clear the uncertainty surrounding current evidence for — and against — Aduhelm.
Take a look at the results of the two largest studies of Aduhelm if you have not already done so. Biogen sponsored twinned Phase 3 studies, called EMERGE and ENGAGE, to see if Aduhlem could slow the rate of loss of life skills and cognition. Both of these studies used an 18-point scale known as the Clinical Dementia Rating (CDR)-Sum of Boxes. This scale records clinicians’ judgments about how much loss of cognition and skills a person facing Alzheimer’s has experienced.
There’s wide agreement that Aduhelm failed in the ENGAGE study. (For more details on this trial, check the posting for it on the ClinicalTrials.Gov website, NCT02477800.)
But Biogen and some FDA officials see strong promise for Audelhm based on an analysis of EMERGE data (NCT02484547).
In the placebo group of the EMERGE trial, the baseline mean score declined 1.74, from a baseline of 2.47, while the high-dose group declined 1.35, from a baseline of 2.51, Biogen told AHCJ. Higher scores indicate more impairment on the 18-point CDR-Sum of Boxes scale, so any preservation of cognitive function would be valued by people with Alzheimer’s disease. But the absolute difference between the two groups is 0.39, or less than a full point, on the CDR-Sum of Boxes scale.
Thus, even the best case to be made from EMERGE data is not very strong, resting on a “very small” difference of patients’ reported decline in cognition and skills, CMS said in explaining the decision to limit Medicare coverage.
Biogen has described the EMERGE trial as having shown a statistically significant 22 percent reduction in clinical decline from baseline. There are two reasons to be wary about using that phrasing, as your audience might misunderstand it.
First, “statistically significant” does not refer to the magnitude of the effect on patients of the drug. Instead, the term “statistically significant” in medicine means the researchers are confident the result seen did not occur by chance. (For more on this, please read this AHCJ primer on statistical significance and this primer on clinical significance.)
And “the 22%” refers to a comparison of the effects in two treatment groups. There’s such a desperate need for a drug that would treat Alzheimer’s disease that people may overestimate what this figure means. In making treatment decisions, people may benefit from seeing results expressed as absolute numbers, represented by the 0.39 point difference for Aduhelm.
In writing about any emerging science, though, we need to remember that we are providing a snapshot of what’s known at this time. The Aduhelm story is a good place to apply lessons journalists learned during the COVID-19 pandemic.
In the past two years, it has become evident that we need to take extra steps to help our readers, viewers and listeners appreciate how science and medicine work.
Results from one or even several studies may later be proven wrong by more extensive research. We need to remind our readers, viewers and listeners of that point and make it clear that we’re giving them an update on an evolving body of knowledge.
In covering medical research, you may want to pause and think about how your story might read to someone looking at it five years or 10 years or even decades from now.
In stories about Aduhelm, thus, it’s worth noting that Biogen expects to start enrollment this year in its ENVISION study, another effort meant to determine whether Aduhelm can hold the damage of Alzheimer’s disease at bay.
And you might mention that Eli Lilly and Genentech are developing medicines similar to Aduhelm. Their drugs also are bioengineered antibodies meant to teach the body to attack amyloid. Let your audience know that more data is expected to be unveiled in the near future about drugs that target amyloid to help treat Alzheimer’s disease.
3. Consider adding details on what research to date shows ways people can lower their risk for Alzheimer’s disease or better cope with this condition.
The CMS memo notes that strategies to address risk factors for Alzheimer’s disease may help people, citing the recommendations of the 2020 Lancet Commission.
“It is never too early and never too late in the life course for dementia prevention,” wrote Gill Livingston, M.D., of University College London and colleagues in that Lancet Commission report.
Recommendations from the report include keeping “cognitively, physically, and socially active in midlife and later life although little evidence exists for any single specific activity protecting against dementia,” they wrote.
The National Institute of Aging’s Alzheimer’s website also offers many suggestions. “Although there is no effective treatment or proven prevention for Alzheimer’s and related dementias, in general, leading a healthy lifestyle may help address risk factors that have been associated with these diseases,” the website says.
Additional resources
- For those new to covering studies of medicines, please take some time to look at the resources on the AHCJ website pulled together by our core topic leader on medical research Tara Haelle.
- Check in with Biogen’s media team if you have questions about its Audhelm data. Also, consider asking for help from nonprofit groups that watch the FDA, such as Public Citizen, the National Center for Health Research and the Center for Science in the Public Interest.
- For more on the FDA’s accelerated approvals of drugs, here’s a tip sheet from The Journalist’s Resource, a publication of the Shorenstein Center of the Harvard Kennedy School of Government.
Please feel free to email patientsafety@healthjournalism.org if you have any questions about reporting on Aduhelm.
