5 Questions: Kevin Schulman on Whether Taxpayers Should Pay for Controversial New Alzheimer’s Drug | Message center

The Food and Drug Administration’s June 7 approval of aducanumab for Alzheimer’s disease sparked a heated argument over the drug’s effectiveness – and its price. The FDA’s independent advisory committee recommended that the drug should not be approved because of concerns about its effectiveness, but the FDA took the unusual step of overriding the committee’s decision. A month after the drug was approved, the FDA restricted its use – another rare step – and restricted it to those with early or mild cases of the disease.

There is significant disagreement over paying for the drug – which Biogen, its developer, plans to sell under the brand name Aduhelm for $ 56,000 for a year-long treatment – and whether Medicare should take the bill, as many scientists believe concerns that it is largely ineffective and provides significant security.

In one (n items published July 19 in JAMA, Kevin Schulmann, MD, Professor of Medicine and Director of the Clinical Excellence Research Center (CERC) at Stanford; Michael Greicius, MD, Professor of Neurology and Neurological Sciences; and CERC visiting scholar Barak Richman, JD, examine what is at stake for regulators, payers and patients. Schulman spoke to CERC author Laurie Flynn about the controversy surrounding the drug’s effectiveness, safety, and cost.

1. What are the clinical results of the aducanumab studies?

Schulmann: Michael, Barak, and I looked carefully at the results of the clinical trials and statistical questions that were presented to the Advisory Committee. Not much of the underlying study designs and analysis were covered in the lay press, and we felt we had an opportunity to make this data transparent.

There were two clinical studies. When a pre-determined combined analysis of the studies was performed, it was determined that the drug had no benefit and the study was discontinued for no reason. Biogen then looked at the two studies individually and found in one of the studies an advantage in the highest dose: a very modest slowdown in the rate of cognitive decline compared to the placebo arm. The other, identical study showed no benefit at the same dose. Interestingly, the placebo groups in the two studies showed different rates of decrease, so it is not clear whether the benefit was from aducanumab or whether it got worse in the placebo patients. In addition, aducanumab is not without risk: up to 40% of the study participants developed brain swelling or microbleeding.

In the end, the FDA approved the drug based on a measured reduction in one biomarker – amyloid plaques in the brain – not based on clinical results that leave “residual uncertainties about clinical benefit.” While amyloid has been linked to Alzheimer’s disease, it is not clear whether amyloid is the origin of this devastating disease or a marker for another destructive process that occurs in nerve cells. No studies of amyloid-lowering drugs have resulted in cognitive improvement in patients.

2. You write that the responsibilities of the Centers for Medicare and Medicaid Services sometimes call for a limitation or a rejection of FDA-approved regulations. What is the right approach to making such difficult decisions, especially with such a widespread and debilitating disease as Alzheimer’s?

Schulmann: There is no question that Alzheimer’s is a terrible disease. Michael and I have treated many patients with this disease and it would be very exciting to offer patients effective treatment options. But with all of the controversy surrounding science today, it is important that the medical community be transparent about the facts, risks, and benefits of therapies, and whether there is room for improvement. We know that patients really want hope, but we also warn in the paper that false hopes could have even graver consequences for patients and their families.

We haven’t looked at FDA approval; Instead, we wondered if CMS should pay for this drug. Alzheimer’s is a disease of old age, so reimbursement is primarily through Medicare and, for many of the most severely affected, through Medicaid. The responsibility of CMS differs from that of the FDA: CMS must decide whether this therapy is to be regarded as a covered service and under what conditions and for which population group. The legal criteria for what can be considered a benefit under Medicare are set out by law: appropriate and required. FDA approval is a minimum threshold for determining whether something is an appropriate and necessary treatment, but it’s not the only criteria for CMS.

CMS needs to be a patient advocate and address what is right for patients, which in this case is challenging given the risks of this therapy and the FDA’s finding that there is “residual uncertainty” about its benefits. CMS must also work on behalf of the other Medicare beneficiaries and the general public to ensure that the drugs they cover have proven effectiveness.

3. For most Alzheimer’s patients on Medicare, this means that part of the cost of the drug is paid for by the taxpayer. What impact would this have?

Schulmann: My mother used to say she paid her Medicare benefits because she paid Medicare payroll tax. Unfortunately, that’s not entirely true. Medicare payroll taxes support Medicare Hospital Benefit, or Medicare Part A. I had to explain to her that her taxes were primarily in support of those enrolled in the system when she paid the taxes and that I will pay for her Medicare hospital after she retired got insurance through my Medicare payroll tax.

Aducanumab is an infusion drug administered on an outpatient basis. It would be considered part of the medical service or part B. This part of the benefit is financed mainly (74%) by general tax revenues and not by wage taxes. If CMS adds aducanumab as a benefit, we’ll all pay for the drugs through our federal income taxes.

In our analysis, we calculated the per capita expenditure that could arise if Medicare chooses to pay for it. If all Alzheimer’s patients with mild cognitive impairment were given this drug, it would cost each American $ 211 a year. In my family of four children, we would pay $ 1,266 a year for therapy that has no proven benefit.

4. What possible interim solutions do you see?

Schulmann: In health care circles, we often talk about moving from the fee for service to the fee for value, and in writing this paper we have tried to look at the fee for value as an approach to reimbursement for that drug. But we also wrote about the challenges of assessing the benefit based on the results of clinical studies. Another idea is to give patients the opportunity to try this drug to see if they will benefit, but again it is not clear whether we can measure the benefit for an individual patient. The data from the clinical trials do not support more traditional measures of value, such as evidence of clinical improvement in cognition or a meaningful change in participation in activities.

Medicare is legally prohibited from negotiating prices with manufacturers. This could be a circumstance if Congress decides to lift this restriction – either by giving CMS the option to negotiate the price directly with the manufacturer, or based on some of the criteria we outline in the paper, e.g. conditional payment program. In this scenario, patients are given therapy for a set length of time, but then treatment would be discontinued if there are no objective signs of improvement or if the disease progresses. If CMS is reluctant to negotiate the price of an approved product, we suggest that CMS can only cover this therapy as part of clinical trials and that Congress may allow CMS to negotiate the price of products used in clinical trials. which would make this a very narrow exception.

5. The Alzheimer’s Association Chief Science Officer, along with other vocal supporters of the drug’s approval, argues that it is better to offer patients something to try now rather than keep them waiting for years. What are the disadvantages of this approach?

Schulmann: We don’t have any inside information, but one wonders how Biogen came to justify a $ 56,000 price tag for a product that at best results in a modest slowdown in patients’ cognitive status. Biogen, along with the Alzheimer’s Association, knows how devastating the disease is and how insensitive to the price Alzheimer’s patients and their families would be for an approved product, even if the benefits are minimal.

The idea that patients with life-threatening diseases can be willing to take risks when choosing a treatment, overestimating the benefits and underestimating the risks, stems from Stanford’s work in behavioral economics. In these conditions, patients do not consider cost when making treatment decisions, and this leaves them vulnerable to exploitative marketing and pricing strategies by pharmaceutical manufacturers.

But that’s not just a pricing story. If this new product went to market for $ 1 a day, there would still be concerns about the safety and effectiveness of this therapy for patients with Alzheimer’s disease.