The pharmaceutical industry, patient advocates and congressional Republicans have all attacked federal authorities’ decision to deny routine Medicare coverage for a controversial Alzheimer’s drug. They went so far as to accuse them of unspoken racism, ageism and discrimination against people with disabilities – and hinted at a lawsuit – for the decision to only pay for patients taking the drug as part of a clinical trial.
The drug, Aduhelm, with a list price of $28,500 a year, has had few takers in the medical world. Brain doctors are wary of administering the drug intravenously because it appears to be dangerous and largely ineffective. Many of the nation’s most prestigious hospitals — such as the Cleveland Clinic, Johns Hopkins Hospital and Massachusetts General in Boston — have refused to offer it to patients.
As groups representing the pharmaceutical industry and patients push to overturn Medicare’s decision, industry critics applaud the Centers for Medicare & Medicaid Services for throwing roadblocks in the way of a drug they think the FDA should never have approved in the first place.
For the industry, the campaign has a larger existential goal: to stop CMS from using its payment decisions to keep FDA-approved drugs off the market. Over the past few years, FDA programs to speed approval of new drugs have resulted in a flurry of entries with often minimal scientific evidence to prove their effectiveness, critics say.
The FDA’s own panel of experts recommended not approving Aduhelm for this reason. Last June, the agency approved it anyway.
CMS then announced that Medicare would only pay when the drug was used in further clinical trials to assess its true benefit. That Jan. 11 announcement drew more than 9,000 comments on the agency’s website — a tsunami compared to most approval decisions. Remarks are roughly divided into pros and cons, and many seem to be organized by groups on the pro side of the debate (like the Alzheimer’s Association) or those against it (like the nonprofit More Perfect). Union). The agency could change or even reverse its decision, although experts say the latter is unlikely.
“If the FDA was doing its job, CMS wouldn’t have had to step in. But good for CMS, they help protect the public from drugs whose harms outweigh the benefits,” said Dr. Adriane Fugh -Berman, a Georgetown University professor of pharmacology who leads PharmedOut, a group that publicizes what he considers to be poor industry practices.
Aduhelm is the first FDA approval for a class of lab-made antibodies designed to clear so-called amyloid plaques, which gradually build up in the brains of people with Alzheimer’s disease.
In clinical trials, Aduhelm did well in dissolving plaque, but its impact on functioning in patients in the early stages of Alzheimer’s disease was so small that an expert panel voted 10-0 (an 11th panelist was uncertain) in November 2020 to advise the FDA to reject this. Science is unclear whether the presence of such plaques – a so-called surrogate marker – correlates with patients’ mental functioning.
As such, the FDA has given “interim approval” to Biogen, the maker of Aduhelm, giving it nine years to provide evidence that the drug slows the progression of Alzheimer’s disease. During this period, Biogen would earn significantly more money than if the application had been denied. Even under the CMS decision, he would reap Medicare payments from whatever is used in clinical trials, which are expected to include thousands of participants to assess the drug’s performance.
Pharmaceutical companies and pharmaceutical investors have reacted to CMS’s decision with particular concern, as they have spent decades improving their relationship with the FDA, only to have CMS appear to be cutting the rug by exerting its own power over an expensive drug. .
“Pharmaceutical companies are concerned that this could set a precedent for other drugs. And it should be,” Fugh-Berman said. “It’s not just about the money; it’s about protect the public.
This “accelerated approval” used for Aduhelm began in 1992 and aims to get promising new classes of drugs to the public more quickly. Companies whose drugs go through the process — more than 250 drugs or vaccines have been approved so far — are expected to quickly gather evidence that the products are likely to improve health once they hit the market. But these follow-up studies are often delayed or never carried out. For example, the makers of the Duchenne muscular dystrophy drug eteplirsen, approved in 2016, only began enrolling patients in a post-marketing trial in 2020 and do not expect results until 2026.
Biogen initially said it would get confirmatory results for Aduhelm within seven years of approval. In response to Medicare’s decision, he promised to reduce that to four years. The company also hinted that it may sue the agency, calling its decision “arbitrary and capricious”.
In the meantime, patients eager to gain access to the drug are furious at the coverage decision. Jim Taylor, a New Yorker whose wife, Geri, says she got better with Aduhelm in a clinical trial, said Medicare made an “unconscionable decision” that puts Alzheimer’s patients” on a dark roller coaster”.
Many patient groups are organized or at least funded and powered by drug manufacturers, providing sympathetic stories that bolster a manufacturer’s business interests. Advocacy groups also receive large donations from the manufacturers of certain drugs. A 2020 report from UsAgainstAlzheimer shows at least $900,000 in donations from monoclonal antibody producers. The Alzheimer’s Association’s top corporate donors – Biogen, Lilly, Eisai and Genentech – all have monoclonal antibody candidates and provided the group with $1.6 million in fiscal year 2021.
These donations represent only a tiny fraction of the group’s funding, its policy director, Robert Egge, told KHN, and any alignment of its position with the industry is “a coincidence, because of what we and our voters think they are fair”.
The Taylors appeared at an online briefing event with activists from UsAgainstAlzheimer’s and the National Minority Quality Forum, a group focused on health inequalities, who argued the decision discriminates against black and Hispanic patients, who are more likely to have Alzheimer’s disease and less likely to join clinical trials. In fact, CMS demanded that Aduhelm’s evidence be collected more broadly from minority patients. Biogen’s two major trials of the drug included only 19 black patients out of a total of 3,285.
Groups representing people with Down syndrome have written more than 1,000 letters to the CMS because its ruling requires confirmatory trials to exclude people with additional neurological conditions. Rep. Cathy McMorris Rodgers, a top recipient of pharmaceutical industry money and the top Republican on the House Energy and Commerce Committee with significant influence on pharmaceutical issues, said during a a hearing last week that it was “extremely concerning and unacceptable” for patients with Down syndrome to do so. be ineligible.
But neither Biogen nor any other pharmaceutical company has recruited Down syndrome patients for a major trial of a monoclonal antibody treatment. AC Immune, a Swiss company, last year conducted a safety study of 16 people with Down syndrome.
It’s no surprise that groups representing people with Alzheimer’s disease have pinned high hopes on monoclonal antibodies, which have seemed like a ray in the dark for the roughly 2 million Americans with the first symptoms of Alzheimer’s disease.
When asked why his group was so enthusiastic about a product in which the medical profession shows so little confidence, Egge said the drug appeared to have some benefits and its risks – especially for patients who had no other means of slowing down a miserable, deadly disease – may be overstated. He acknowledged that 40% of patients in the larger Aduhelm trial experienced swelling or bleeding in the brain, but Biogen’s research showed that these resolved without apparent damage in most cases.
That said, slow purchases of the drug — which fetched a modest $1 million in the last quarter of 2021 — signals that the market is reacting to its shortcomings.
In response to the lackluster response, Biogen halved its original price from $56,000 to $28,500. Had CMS granted full approval, it would have been followed by “marketing, marketing, marketing,” said Dr. Joseph Ross, a professor of public health at Yale University. Hospitals that wanted to attract patient companies for a lucrative infusion — patients receiving the drug also require brain scans and other tests and follow-ups — could advertise their willingness to donate Aduhelm.
The CMS decision fell under a policy called hedging with development of evidence. Although the program started in 2005, Aduhelm is by far the largest product that CMS has refused to reimburse without further investigation.
The agency’s decision “is a bit inelegant” because it hampers FDA approval, said former CMS chief medical officer Dr. Sean Tunis, now a consultant and principal investigator at Tufts Medical Center, but ” it seems quite justifiable since the evidence for benefits is quite weak and the evidence for harm is quite strong.
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