The Food and Drug Administration’s controversial June 7 approval of aducanumab (Aduhelm) means that for the first time in 18 years, Alzheimer’s patients have a new treatment option. Nonetheless, due to the high cost of the drug and associated testing, few people will be able to get the treatment unless insurance companies cover it. Whether that will happen remains uncertain, given that aducanumab was approved based on a biomarker effect, without convincing evidence of efficacy. Many big insurers, including the Centers for Medicare and Medicaid Services, are currently weighing their options and seeking input. In private and public meetings, insurers have been consulting with Alzheimer’s researchers, health care analysts, and advocates to glean more information about the drug’s efficacy and safety. Their eventual decisions could determine how widely used aducanumab becomes.

  • Most insurers are still gathering data to inform their coverage decisions.
  • CMS has opened a National Coverage Determination, which will influence private payers.
  • Health economics group ICER judges aducanumab not worth the cost.

“Many institutions are waiting to hear how reimbursement will be arranged; once that is solved, I think there will be a substantial uptick in use,” Jeffrey Cummings at the University of Nevada, Las Vegas, told Alzforum. Cummings led the expert panel that devised appropriate-use recommendations for aducanumab (Part 1 of this series). Meanwhile, controversy over the approval process for aducanumab continues to brew (see Part 8 of this series).

Payers Are Weighing Options
The uncertainty over efficacy, plus the drug’s $56,000 per year price tag, has left insurers scrambling. Some affiliates of Blue Cross and Blue Shield, and Massachusetts’ Point32Health, have already said they won’t cover the treatment (STAT news; Boston Globe). The Department of Veterans Affairs announced August 11 that it will not carry aducanumab in its formulary, though local VA centers can request access to the drug. The VA recommends against prescribing aducanumab, except in “highly selected patients” who are receiving care at centers with the requisite expertise (Endpoints News). Most insurers are still deciding (Axios newsSTAT news).

To help inform their decision, the Margolis Center for Health Policy at Duke University on July 14 convened representatives from about a dozen insurance companies including CMS, plus Alzheimer’s researchers, Biogen staff, and the FDA for a private meeting. It gave insurers a chance to go over the trial data and ask questions about the patient population, efficacy, and safety. Payers were particularly interested in the costs of monitoring for ARIA by MRI, noted Eric Siemers of Siemers Integration LLC, who attended the meeting. The appropriate use guidelines presented at AAIC recommend more MRIs than the FDA label specifies.

“Since this is the first disease-modifying drug with any sort of approval for AD, payers will need time to understand the financial implications,” Siemers wrote to Alzforum. Cummings, who also attended, agreed. “The meeting provided a neutral setting for dialogue. No consensus was reached, but this was a good beginning,” Cummings said.

Private payers are likely to take their cues from CMS. An estimated 80 percent of the patients eligible for aducanumab are covered by Medicare. To establish a consistent nation-wide policy, CMS launched a National Coverage Determination for aducanumab July 12 (CMS announcement; Endpoints News). The agency uses this process for only a few drugs each year. The NCD began with a 30-day public comment period and two public listening sessions. CMS will issue a draft coverage proposal after six months, and will encourage public comments on that proposal for another 30 days. A final decision is expected after nine months, in April 2022.

Of note, CMS has indicated that its decision will cover other anti-amyloid monoclonal antibodies, as well. This has sparked pushback from Eli Lilly, which is filing for accelerated approval for its own anti-amyloid antibody, donanemab. In a public comment, a representative for Lilly urged CMS to consider the merits of each immunotherapy separately (Endpoints News).

In the meantime, decisions about whether to cover aducanumab are up to regional Medicare centers. “Right now, most are saying no,” noted Mark McClellan, who was FDA commissioner from 2002 to 2004 and now runs the Duke-Margolis Center that hosted the private meeting.

One possible outcome for the NCD would be for the agency to grant Coverage with Evidence Determination (CED), the same process currently used to cover amyloid PET scans in the IDEAS study. In this scenario, treatment would be covered as part of a clinical trial that gathers evidence of aducanumab’s effectiveness. McClellan helped develop the CED process while at CMS. He noted that such trials are usually not randomized. Instead, they may match people who decide to get the treatment versus those who don’t, or compare different dosages and timing of treatment.

McClellan lamented that although the FDA has become more open to innovative trial designs, there has been no comparable innovation for figuring out how to cover expensive, groundbreaking therapies. “I hope [aducanumab] is a wake-up call. More innovative treatments are coming,” McClellan said at a July 15 meeting of the Institute for Clinical and Economic Review (ICER).

ICER Doubles Down: Aducanumab Not Worth the Cost
The purpose of the day-long ICER meeting was to review efficacy data for aducanumab and debate whether the treatment is cost-effective. Besides ICER scientists, representatives from Biogen, advocacy groups, and insurance companies attended, along with 15 members of the California Technology Assessment Forum. This forum included an academic geriatrician, neurologist, several other physicians, health policy and economics experts, an ethicist, and three patient advocates. Also attending the ICER meeting were two Alzheimer’s researchers, one of whom, Sarah Kremen of Cedars-Sinai Medical Center, Los Angeles, was a site PI for the aducanumab trials.

In discussion, a sharp division of opinion became evident. On one side, representatives from Biogen, the Alzheimer’s Association, and Us Against Alzheimer’s, as well as a patient and caregiver affected by AD, spoke in favor of aducanumab. On the other side, independent experts from ICER and CTAF were unanimous in finding the efficacy data lacking. Kremen struck something of a middle ground, noting that some patients may benefit from aducanumab, but it would be challenging to determine who those could be, and whether the benefit would outweigh the health risks from ARIA. “From the standpoint of ‘do no harm,’ prescribing makes us uneasy,” Kremen noted in the discussion.

Across the board, participants expressed intense concern over aducanumab’s cost. ICER president Steve Pearson noted that 21 million Americans are in medical debt, and aducanumab is likely to exacerbate this. The drug's estimated $11,300 yearly out-of-pocket cost for Medicare beneficiaries would amount to 40 percent of the median income for a retiree. Six million Medicare beneficiaries lack supplemental insurance, and for those who have it, the out-of-pocket maximum would still be $7,500 per year, Pearson said.

At the ICER conference, the drug’s price was the one issue where ICER and the Alzheimer Association agreed. “We believe the price will hinder access,” said Matthew Baumgart of the association.

Notwithstanding the cost to individuals, the total price tag could reach $57 billion per year if 1 million patients go on drug. That would drain CMS coffers. Biogen's Chris Leibman defended the price, arguing that Biogen expects no more than 10 percent of the roughly one to 2 million eligible patients, or around 150,000 people, to take aducanumab. “If we see different numbers, we will work with CMS and private payers to address pricing,” Leibman said.

An insurance industry analyst noted that patients demand the drug. “We’ve never had more calls from subscribers on day one than we did for aducanumab,” said Leslie Fish of IPD Analytics. The demand makes payers worry that it will be challenging to restrict coverage to the right patient group. “Almost all payers want to set prior authorization,” Fish noted. This would allow insurers to judge the medical necessity and appropriateness of treatment on a case-by-case basis.

Other insurance representatives pushed for value-based pricing. “We’d like patients to have access to it, and we’ll work on a fair price,” said Pat Gleason of Prime Therapeutics, based in Eagan, Minnesota.

Sei Lee of the University of California, San Francisco, summed up the feelings of many. “For extraordinarily high cost, I would expect extraordinary evidence [of efficacy], and I haven’t seen that,” Lee said.

The ICER meeting concluded by having the CTAF members vote on whether the efficacy data was sufficient to conclude that treatment with aducanumab was better than the standard of care. Unanimously, they said it was not. Panelists also voted to say the treatment was likely to do more harm than good, due to its high cost and risk of ARIA.

ICER's Pearson, and many CTAF members, spoke about their own loved ones having suffered from Alzheimer’s, or having the disease now. Some currently take care of an affected parent. They understand the urgency to find better treatments. Patient advocate Richard Seiden said, “I’m optimistic that research will produce better disease-modifying drugs, and I trust clinicians will appropriately manage the expectations of patients and caregivers [around aducanumab].”

In a final report issued August 5, ICER reaffirmed and elaborated its May 5 interim conclusion that aducanumab is not cost-effective (Endpoints News; Endpoints News). Pearson called on Biogen to lower the price. Given that more anti-amyloid antibodies are coming, the broader question of how efficacious this drug, and its class, is remains open. “ICER will come back to this topic,” he promised.—Madolyn Bowman Rogers

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References

News Citations

  1. Aducanumab: Will Appropriate-Use Recommendations Speed Uptake?
  2. Flurry of Investigations Beset Aducanumab

Therapeutics Citations

  1. Donanemab

Other Citations

  1. aducanumab

External Citations

  1. STAT news
  2. Boston Globe
  3. Endpoints News
  4. Axios news
  5. STAT news
  6. CMS announcement
  7. Endpoints News
  8. 30-day public comment period 
  9. Endpoints News
  10. Endpoints News
  11. Endpoints News

Further Reading