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Mixed Response to the CMS Decision on Coverage for Aducanumab

​The federal government's proposal to significantly limit Medicare coverage for  aducanumab and similar treatments for Alzheimer's disease (AD) is disrupting operations for some neurology practices—and prompting others to consider administering the new therapy for the first time.

After months of controversy over the US Food and Drug Administration's (FDA) accelerated approval of aducanumab, the Centers for Medicare and Medicaid Services (CMS) announced its draft plan on January 12 to use a “coverage with evidence development" (CED) approach to paying for the drug and similar products in the pipeline. That means that FDA-approved drugs that target amyloid to treat AD will be covered for Medicare patients only if they are enrolled in a CMS-approved randomized controlled trial. CMS is accepting public comments on its proposal through February 11; its final decision will be issued April 11.

 The announcement shocked Jeffrey B. Gelblum, MD, a neurologist at First Choice Neurology in Aventura, FL, who has been prescribing aducanumab since its FDA approval last summer. 

“We are actively infusing many patients—that's going to stop immediately," Dr. Gelblum said. “Our phones have been ringing off the hook with Alzheimer's patients saying, 'Well, what now? Do I continue or not?'" Dr. Gelblum said the day after the CMS announcement.

Medicare patients in Florida have had access to the therapy, courtesy of a local coverage decision. Those local decisions will remain in place until the CMS national coverage deciision is finalized. Dr. Gelblum intends to continue prescribing aducanummab as long as he can.

Meanwhile, Cedars-Sinai Health System in Los Angeles, which has not administered aducanumab until now, is interested in a clinical trial for aducanumab.  Zaldy S. Tan, MD, MPH, director of the health system's Memory and Aging Program, said participation will depend on the trial protocol and inclusion/exclusion criteria, but he likes the CMS decision to give appropriate patients access to the drug “while harnessing very important efficacy and safety data."

“Given the remaining uncertainty on the efficacy of this medication, this approach will help guide future disease-modifying therapies for Alzheimer's disease," Dr. Tan said.

Biogen, which markets aducanumab as Aduhelm, decried the CMS coverage proposal. “It is imperative to change this draft decision to be aligned with reimbursement for other therapies for progressive diseases, where patients have immediate and equal access to medicines approved by the FDA," the company said in a news release.

How We Got Here

Medicare's payment policy for aducanumab has been one of the most-anticipated decisions in health care ever since Biogen launched the drug at $56,000 a year last June. Some public and private payers have been covering it; that includes some local Medicare administrative contractors, which set payment policies for a specific geographic region unless a national coverage determination for a particular therapy supersedes their decisions. Other payers have declined to cover the drug, saying that the failure of two clinical trials to demonstrate clear clinical benefit renders aducanumab to be “experimental" rather than medically necessary.

The CMS national coverage policy is the most important factor for the drug's immediate future because an estimated 80 percent of the patients eligible for aducanumab are covered by Medicare. Nearly two million Medicare beneficiaries used at least one AD treatment in 2017, according to an analysis by Kaiser Family Foundation (KFF).

If just one million Medicare-covered patients received aducanumab, spending on the drug would top $57 billion a year, nearly the same amount that Medicare paid for all hospital outpatient services in 2019, KFF said.

CMS braced for a financial pummeling. In November, it announced a large increase in Medicare Part B premiums, which cover outpatient care, for 2022, with nearly half of the increase attributed to “the possibility of coverage and subsequent utilization of monoclonal antibodies directed against amyloid for the treatment of Alzheimer's disease," according to an agency spokesperson.

Meanwhile, Biogen's hopes for blockbuster-level sales dimmed as some academic medical centers announced they would not prescribe aducanumab and many others slow-rolled their decision as neurologists debated whether the drug was worthwhile at any price.

On December 20, a group of dementia and other health care experts, led by Peter J. Whitehouse, MD, PhD, professor of neurology at Case Western Reserve University, and Sam E. Gandy, MD, PhD, Mount Sinai Professor of Alzheimer's Disease Research and professor of neurology and psychiatry at Icahn School of Medicine at Mount Sinai, called on the FDA to withdraw its marketing approval for aducanumab. They started a petition drive to pressure the agency and issued a public statement: “This drug should be withdrawn from the market immediately."

That same day, Biogen announced it was slashing aducanumab's price by half to $28,600 a year. Acknowledging the uproar over the drug's rollout, the company effectively quashed any lingering dreams of blockbuster sales.

In a press release, the company said "with insurance coverage, and access to diagnostics and specialized centers, approximately 50,000 patients" might start aducanumab treatment in 2022. It also announced it would cut costs by $500 million this year, in part because of the “delayed uptake" of aducanumab.

On January 10, Department of Health and Human Services Secretary Xavier Becerra ordered Medicare to reconsider its 2022 premium increase, citing Biogen's reduced price for aducanumab. In his written statement, Becerra did not hint at the prospect Medicare would sharply curtail access to the drug via its national coverage determination, but that announcement came the very next day.

In an email, a CMS spokesperson said the agency is reassessing the Part B premium, and more information will be forthcoming. 

​Neurologists Weigh In

David S. Knopman, MD, FAAN, a professor of neurology at Mayo Clinic who resigned from the FDA Peripheral and Central Nervous System Drugs Advisory Committee over the way the FDA handled the aducanumab approval, agrees with the logic and approach CMS has laid out.

“It was the right decision, given the lack of demonstrable clinical benefits of aducanumab that have so far been demonstrated," Dr. Knopman said.

The CMS proposed coverage policy aligns with several positions for which the AAN has advocated, said Brad C. Klein, MD, MBA, FAAN, chair of the AAN work group on aducanumab. Those include coverage of an amyloid-beta PET scan to confirm amyloid in prospective trial subjects; limiting coverage to patients with mild cognitive impairment (MCI) or mild AD dementia; more clinical trials to confirm that aducanumab has a clinical benefit; and the need for more inclusive trial data to reflect the diverse patient population affected by AD.

That said, “We need to dig in to fully understand the impact of the CED on patient access and future drugs," Dr. Klein said.

Dr. Klein, a partner in Abington Neurological Associates in suburban Philadelphia, said patient demand for aducanumab has been relatively low. “After discussions with patients, some  will ask for the medication while others feel it is worth waiting until the data [are] clearer," he said.

He is disappointed that CMS appears to prohibit community-based practices from participating in the clinical trials to learn whether the drug actually works. “Despite the size of my practice's research center and more than a decade of experience in clinical trials, we may be excluded because we are not hospital-based," he said.

At the University of Rochester School of Medicine and Dentistry, the Alzheimer's Disease Care, Research and Education Program (AD-CARE) is participating in an extension study of aducanumab as well as studies of three other monoclonal antibodies—gantenerumab, lecanumab, and donanemab—that target amyloid function. It has been waiting for the CMS coverage policy before administering to patients outside of trials, said Anton P. Porsteinsson, MD, director of the AD-CARE program.

“A specific team with extensive experience in managing such treatments has been assembled and a treatment guide/protocol has been developed," said Dr. Porsteinsson, the William B. and Sheila Konar Professor of Psychiatry, Neurology, Neuroscience, and Medicine. But the breadth of the CMS proposal means that it will pay for the three drugs awaiting FDA approval outside of additional clinical trials, even if their phase 3 trials demonstrate clinical benefit.

“Until the coverage decision possibly changes with phase 3 data from gantenerumab, lecanumab, and donanemab …I expect that demand will be very muted," he said.

Jeffrey L. Cummings, MD, ScD, the Joy Chambers-Grundy Professor of Brain Science at the University of Nevada Las Vegas, is disappointed to see CMS limit coverage to patients participating in trials, which disadvantages those who do not live close to an academic medical center. Dr. Cummings, who was one of the investigators on trials of the drug, has advocated for the approval of the drug. “The decision perpetuates the inequities seen in most trials with limited availability to rural and underserved patients," he said.

In Florida, Dr. Gelblum is dismayed by the effect the CMS coverage policy will have on his patients. “We are actively infusing many patients in accordance with FDA approval...and now we immediately have a cessation of care," he said. “That's a big problem."

Beyond his concern for his current patients, he believes CMS is preemptively denying future patients access to drugs that might slow the progression of their disease.

“Biogen may have done a better job with its clinical trials and its approval process, but we've got other pharmaceutical manufacturers of good repute," he said. “If [Eli] Lilly has gangbuster data with their new (donanemab), we're not going to be able to access it because this new CMS decision essentially shuts that off. So that's the end of that."

Disclosures: Dr. Knopman served on a data safety monitoring board for the DIAN study. He serves on a data safety monitoring board for a tau therapeutic for Biogen, but receives no personal compensation. He is a site investigator in the Biogen aducanumab trials. He is an investigator in clinical trials sponsored by Lilly Pharmaceuticals and the University of Southern California. He serves as a consultant for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences, but receives no personal compensation. He receives research support from the National Institutes of Health. Dr. Cummings has consulted for Acadia, Actinogen, Acumen, Alector, Alkahest, Alzheon, AriBio, Avanir, Axsome, Behren Therapeutics, Biogen, Cassava, Cerecin, Cerevel, Cortexyme, Cytox, EIP Pharma, Eisai, Foresight, GemVax, Genentech, Green Valley, Grifols, Janssen, Karuna, Merck, Novo Nordisk, Otsuka, ReMYND, Resverlogix, Roche, Samumed, Samus, Signant Health, Sunovion, Suven, and United Neuroscience pharmaceutical and assessment companies.