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Controversial Alzheimer’s drug highlights concerns about Health Canada approval process


There’s a new drug on the block to treat Alzheimer’s disease. On June 7, the United States Food and Drug Administration approved aducanumab (brand name Aduhelm), made by Biogen, the first new drug for Alzheimer’s in 18 years. Biogen has submitted aducanumab for approval here in Canada.

Alzheimer’s is a devastating disease. I see people suffering from dementia almost every day when I’m working in the emergency department in downtown Toronto, and I’ve watched friends stripped of their lives by this disease. So, a drug that could help to relieve their suffering should be cheered on, as the U.S.-based Alzheimer’s Association and the Alzheimer’s Society of Canada have hailed aducanumab.

But aducanumab is not such a drug. There is no convincing evidence that aducanumab will make any difference for Alzheimer’s patients.

Surrogate endpoint

Aducanumab was approved on the basis of what’s called a surrogate endpoint, which is a measurement that is supposed to reflect progression of a disease. In this case, the surrogate endpoint was the clearing of amyloid plaque — abnormal brain deposits often seen in Alzheimer’s patients — from the brains of those with Alzheimer’s. Aducanumab was successful in doing that, but it’s not the first drug that has been shown to clear plaque.

There have been more than 25 previous trials of plaque-clearing drugs and none of them showed any benefit for people with Alzheimer’s. One study followed elderly individuals with plaque and pathological changes typical of Alzheimer’s and found that they had no more cognitive decline that those with “normal” brains.

Aducanumab is also not without risks. In the clinical trials, over one-third of patients taking the drug experienced brain changes seen on scans, including some level of brain swelling, versus less than three per cent of those who got the placebo. Almost one per cent of those with changes had severe symptoms, including confusion, disorientation, gait disturbance, ataxia, visual disturbance, headache, nausea, falls and blurred vision.

FDA controversy

When the clinical evidence about the drug was presented to a FDA advisory committee of outside experts, 10 out of the 11 members voted against the drug’s approval and the 11th was uncertain. Despite this vote, the FDA went ahead and approved aducanumab, prompting three of the committee members to resign in protest.

Although the drug had only been tested in those with mild symptoms, the FDA said it could be used for patients with any degree of Alzheimer’s. Within a few weeks, the FDA walked back that decision. Finally, it gave Biogen until 2030 to conduct a study to show that aducanumab actually works.

Read: FDA approves much-debated Alzheimer's drug panned by experts

There are concerns that paying for aducanumab might threaten the financial viability of the Medicare Part B, the plan that pays for prescription drugs for U.S. seniors. The total cost in 2018 for all Medicare Part B drugs was US$35 billion. Biogen is charging US$56,000 annually for aducanumab. There are about 5.8 million people with Alzheimer’s who are eligible for Part B coverage. Prescribing aducanumab to just one million of them would cost Medicare an estimated US$57 billion per year.

The independent Boston-based Institute for Clinical and Economic Review calculated that a fair annual price based on the drug’s presumed effectiveness would be between US$2,500 and US$8,300. Added to the US$57 billion are costs for intravenous infusion of the drug and the PET and MRI scans to see if the drug is clearing brain plaque and to watch for side-effects.

Health Canada application

The possible approval of aducanumab by Health Canada highlights a series of debates and concerns about how we approve new drugs. The Fraser Institute, a free-market think tank, would like Health Canada to dispense with its own reviews and automatically accept any drug approved by either the FDA or the European Medicines Agency.

Given the contortions that the FDA went through to allow aducanumab on the U.S. market, that might not be such a good idea. The recent report from the House of Commons Standing Committee on Transport, Infrastructure and Communities on Boeing’s 737 Max also highlights the dangers of abandoning regulatory oversight to other governments, in this case Transport Canada’s reliance on the U.S. Federal Aviation Authority.

The FDA Advisory Committee, composed of outside experts, almost unanimously recommended rejecting Biogen’s application to market aducanumab. Health Canada also uses expert advisory panels and committeesfor policy issues and technical advice, but not for opinions about whether to approve a new drug. That means that Health Canada will not be getting any outside expert advice about aducanumab.

After the disappointing results of trials on the drug in 2019, Biogen initially decided to abandon work on aducanumab. Subsequently, there are allegations that FDA officials held almost daily back-channel meetings with Biogen throughout the summer of 2019 to determine if there was a way to reinterpret the data and resuscitate the drug.

The acting head of the FDA is requesting an investigation by the inspector general for the Department of Health and Human Services into whether these meetings were inconsistent with the FDA’s policies and procedures.

Read: Scientists get closer to blood test for Alzheimer's disease

Health Canada also meets with companies before they submit drugs for approval so that sponsors can outline the evidence of effectiveness. If meetings have taken place with Biogen there will not be any public record of what was said in them or even if they occurred.

Finally, regardless of whether Health Canada approves or rejects Biogen’s application, we will never see what sort of debate went on inside the agency about the safety and effectiveness of the drug. Health Canada will eventually release virtually all of the data that Biogen submitted, but any internal discussions will remain a secret.

Canadians with Alzheimer’s and the clinicians who treat them deserve a drug that works for patients, not for Wall Street.

Joel Lexchin is a professor emeritus of Health Policy and Management, York University, emergency physician at University Health Network and associate professor of Family and Community Medicine, University of Toronto.

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