More on FDA approval of Aducanumab

ElaineD

From the New York Times today:

https://www.nytimes.com/2021/06/10/health/aduhelm-fda-resign-alzheimers.html?action=click&module=Science%20%20Technology&pgtype=Homepage

Three F.D.A. Advisers Resign Over Agency’s Approval of Alzheimer’s Drug

Elaine

M1

One can hope that common sense may prevail.  I think the insurance companies are going to put very restrictive guidelines in place on whom they might cover:  remember, only 1 in 10 people screened for the initial studies were early enough in their disease process to qualify.  This is not going to help very many people, and few will be willing to go every month for infusion therapy.

Jeff86

One more thing (Colombo).  I have serious concerns about patient advocacy groups generally and our Alzheimer’s Association specifically pushing hard for this approval.  Makes me reconsider where I want to send my support $.

Rescue mom

In my experience, by the time PWDs have symptoms bad enough to get tested and diagnosed for dementia, they’re beyond those earliest stages this drug talks about.

And, as M1 said, monthly infusions are no small thing. I did it for almost a year for an auto-immune disease. It’s tough, although I know cancer patients (who may have more at stake, or to gain with better-known drugs) do it. 

I can’t get excited about this, but undoubtedly there are people with money who’ll do it regardless. The drug company will, I expect, make major money, some of which I also expect will go to politicians.

Crushed

The F.D.A. Has Reached a New Low

NYT June 15, 2021, 7:19 a.m. ET

Dr. Kesselheim and Dr. Avorn are professors of medicine at Harvard Medical School. Dr. Kesselheim recently resigned from an F.D.A. advisory committee over the agency’s approval of aducanumab.

Decades ago, drugmakers in the United States could sell medicines without demonstrating that they actually worked.   That came to an end in the early 1960s after tens of thousands of women worldwide gave birth to children with severe birth defects after taking the inadequately tested drug thalidomide. Few of these tragedies occurred in the United States, thanks to the work of Dr. Frances Kelsey, an astute Food and Drug Administration scientist who kept the drug off the American market. The thalidomide debacle persuaded Congress to pass a law in 1962 requiring companies to test their drugs extensively before they could be sold.

Since then, American patients and doctors could assume that the medications we take or prescribe have been found to be sufficiently safe and effective by the F.D.A. That careful review process set the standard for drug evaluation worldwide.

But the strength of that process has been eroded, and it reached a low point last week when the F.D.A. approved aducanumab, a treatment for Alzheimer’s disease that has not been convincingly shown to work and can cause brain swelling and hemorrhage.

In recent years, under steady pressure from the pharmaceutical industry and the patient groups it funds, the F.D.A. has progressively lowered its standards of effectiveness and safety required for drug approvals. New drugs are now more likely to be supported by fewer studies and less adequate clinical trial designs than in the past. Worse, about two-thirds of new drugs are now approved based on what’s called “surrogate endpoints” — changes in the body measured by lab tests that suggest a potential benefit — rather than whether a drug meaningfully affects how a person feels, functions or survives.

For aducanumab, the evidence that its manufacturer, Biogen, submitted to the F.D.A. showed no convincing effect on patients’ cognitive decline. Its two main trials were stopped early in 2019 because the company concluded its drug did not work. But the company later reanalyzed its data and concluded that some patients in one arm of one of the trials seemed to benefit from the drug, even though the other trials did not show any improvement.

The F.D.A. worked closely with the company to study the data. But after careful review, an outside advisory committee for the agency was nearly unanimous in its ruling that the drug had failed to show strong evidence that it worked. Committee members were also concerned about the drug’s safety, since about a third of patients taking a higher dose had evidence of brain swelling. One of us, Dr. Kesselheim, was a member of that committee and has resigned as a result of the F.D.A.’s inexcusable decision to approve the drug anyway.

In approving aducanumab, the F.D.A. shifted the goal posts. It unexpectedly approved the drug based on a theory that it could affect amyloid protein levels in the brain. Amyloid buildup in the brain is considered a marker for Alzheimer’s disease, but lowering amyloid levels with a drug has never been shown to slow cognitive decline. Dozens of investigational drugs have lowered amyloid levels without affecting the progression of this terrible disease.

Even worse, although aducanumab was tested only in patients with mild disease, the F.D.A. inexplicably approved it for use in any person with Alzheimer’s, regardless of severity. It enters the market now as a monthly intravenous infusion with a $56,000 price tag and the need for regular M.R.I. scans to monitor for the possible brain swelling it can cause.

Continue reading the main story

The F.D.A. does require follow-up research for drugs approved based on such unsubstantiated measures, but the agency gave Biogen a full nine years to complete another trial. Millions of patients will have been treated and billions of dollars passed along to Biogen before we know whether it really works. Now that the bar has been lowered, other companies are likely to seek similar pathways to approval.

The aducanumab decision is the worst example yet of the F.D.A.’s movement away from its high standards. As physicians, we know well that Alzheimer’s disease is a terrible condition. But approving a drug that hardly works and causes such worrisome side effects is not the solution.

If pressure from drugmakers and their lobbyists compels F.D.A. administrators to continue to loosen their standards, we need a new organization to review drug approvals and make evidence-based assessments of their clinical impact, as other countries do. These assessments can help guide patients to decide whether they want to spend their money on these drugs, help physicians understand whether to prescribe them and help insurers determine whether to cover them.

The need for outside oversight is clear, given the continuing failure of the F.D.A. to listen to its advisers, stand up to industry and consumer-group pressure and draw clear distinctions between drugs that work and drugs that only cause changes in lab tests of uncertain relevance. We cannot let this regulatory erosion send us back to a pre-thalidomide era.

Aaron S. Kesselheim and Jerry Avorn are internists and professors of medicine at Harvard Medical School, where they direct the Program on Regulation, Therapeutics and Law at Brigham and Women’s Hospital. Dr. Kesselheim served on the F.D.A. advisory committee that reviewed aducanumab from 2015 until he resigned this month.

Donr

So sad to read that.

Michael Ellenbogen

I was told that when cancer first started with drugs for approvals some of this had happened then so this is not the first time dugs kind of slipped by in the pipeline.  

Lane Simonian

Label restrictions have been added to Aduhelm.  This was the right decision.

Aduhelm, also known as aducanumab, was studied in patients with early disease who tested positive for a component of amyloid brain plaques, but the FDA approval last month did not restrict its use to a specific group of patients.

Treatment with the drug should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, according to the updated product information on the drug.

The updated label, which was approved by the FDA after the company submitted it, also said there was no safety or effectiveness data on initiating treatment at earlier or later stages of the disease.

https://www.nasdaq.com/articles/u.s.-fda-narrows-label-for-biogens-alzheimers-drug-2021-07-08

Crushed

FDA head calls for inspector general investigation of agency’s dealings with Biogen, maker of controversial new Alzheimer’s drug Was Post

July 9, 2021|Updated today at 1:35 p.m. EDT

Janet Woodcock, acting commissioner of the Food and Drug Administration, on Friday asked for the inspector general to conduct an “independent review and assessment” of the agency’s interactions with the maker of a controversial new Alzheimer’s drug, whose approval has set off a torrent of criticism.

Woodcock said on Twitter she was requesting the review because of the “ongoing interest and questions” about the approval of the drug, called Aduhelm, on June 7. She said the review would focus on interactions between representatives of Biogen and the FDA during the process that led to the approval.

In a letter to the Office of Inspector General at the Department of Health and Human Services, Woodcock said there has been “significant attention and controversy surrounding the process” for Aduhelm.

She said she had “tremendous confidence in the integrity of the staff and leadership” of the agency involved in the approval but added that questions continue to be raised about contacts between Biogen and the FDA, “including some that may have occurred outside of the formal correspondence process.”

Stat, a website covering medical and science news, reported last month that there was an informal meeting in May 2019 between Alfred Sandrock Jr., a top Biogen official, and Billy Dunn, the head of the FDA’s neuroscience office, at a conference in Philadelphia.

The news site also said the agency early in the approval process outlined several possible paths to clearance, including accelerated approval — even though officials told an outside advisory committee later that the option was not under consideration.

Critics say there is scant evidence that the drug, which received accelerated approval from the FDA, will slow cognitive decline in patients, which is what the medication was designed to do. They have accused the FDA of bending over backward to clear the treatment, contending that regulators worked too closely with Biogen to get the drug on the market.

The controversy has been exacerbated by the list price — $56,000 a year per patient — which many worry could jeopardize the financial health of Medicare.

The FDA on Thursday moved to quell some of the outcry by limiting the recommended use of the drug to patients with mild cognitive impairment or early dementia from the disease — a major change from the original label that included anyone with the illness.

The revised label clarifies that Aduhelm is intended for patients with early-stage disease — the population that participated in clinical trials of the drug. It is the first Alzheimer’s medication cleared since 2003.

The narrower label limits the recommended population eligible for the drug to 1 million or 2 million Alzheimer’s patients, rather than the more than 6 million people with Alzheimer’s in the United States, Michael Yee, a biotech analyst for the financial services company Jefferies, said in a note to investors.

The agency approved the drug despite a recommendation from an outside advisory committee that FDA reject the medication. Three members of the panel resigned following the approval, saying they strenuously disagreed with it. Members of Congress have called for investigations into the approval.

  

Michael Ellenbogen

I knew this was coming and it is so great that they made changes to whom the drug is good for. All good.