politics not science drives Aduhlm campaign

Crushed

Inside a Campaign to Get Medicare Coverage for a New Alzheimer’s Drug

 

The Alzheimer’s Association has pushed relentlessly to get broad access to Aduhelm, despite safety risks and uncertain evidence that it helps patients.

 The association’s campaign makes little mention of Aduhelm’s safety risks and uncertain benefit, arguing that restricting coverage of an F.D.A.-approved drug is “shocking discrimination against everyone with Alzheimer’s disease.”

In sessions prepping for those meetings, association officials suggested that people say versions of phrases like “I have a fatal disease and I want more time with my family” and to discuss “how access to F.D.A.-approved treatments will impact me and my family.”

The Alliance for Aging Research led a rally of about 100 people outside the Department of Health and Human Services, which houses C.M.S. (Afterward, about half the alliance’s scientific advisory board quit in opposition to the group’s position.).....

Both a council of senior F.D.A. officials and the agency’s independent advisory committee had said there wasn’t enough evidence for approval. ...

 
In recordings of the staff meeting and two prep sessions, (Alzheimer's) association officials didn’t mention Aduhelm’s safety risks.

  
 

https://www.nytimes.com/2022/04/06/health/aduhelm-alzheimers-medicare-patients.html

Paris20

It’s unconscionable that formerly-trusted organizations and agencies have acted so irresponsibly. I heard or read that approval and promotion have had more to do with offering something, anything, to patients who had no hope than providing real therapies that work. This is no solution to the myriad of horrors that are the result of dementia. If some real evidence shows me that my husband can be helped, I’ll be on board. If not, then I shall continue to tell friends and family who tell me «You’re not insisting that DH’s neurologist prescribe this new miracle drug I heard about?» No, I will not.

Jo C.

This topic has raised significant questions for myself from the start and as things moved on to rapidly push the drug into approval before completing study/FDA processing,, I have felt appalled by some of the dynamics re input from different sides.  It can be confusing.

NOTE:  It is important to read not only the NY Times article which has been provided as a link in this Thread, but to also read other articles from other sources.  This particular article provided by Crushed is informative re various aspects of this drugs rapid processing and pushing toward the marketplace.   One more time that it really reminds us that we need to keep up to date not only with this particular drug, but also with future drugs that will come to the marketplace.  The paragraph re relationships, etc., was startling for me; I had not been aware of that.  (This is not the only critical article from either side printed in valid publications regarding various dynamics of this rapid processing to the marketplace.)

Why the degree of formal, extensive, very well planned, and expensively executed pushing from various multiple source s is perplexing in the various manners in which they have been carried out.  Certainly wish the drug company and the FDA had seen to completion of due diligence in completion of the drug studies and processing prior to getting it pushed into availability to the public.

Thank you Crushed for providing this important information which can be helpful in our becoming more informed re different aspects involved in this evolving situation; it helps one to come to an understanding re what to support and what not to support for our LOs knowing more facts about the the various politics as well as incomplete science involved with some new drugs coming onto the market and what is driving such trains so to speak on how drugs are approved and supported. 

We all hope for the day that a safe, reliable and effective drug becomes available; what a miracle that will be for everyone.  However, this drug being pushed before the FDA process was complete and with its possible serious effects of brain bleeds and brain swelling would not be what we would want used in our family.

Most important in my reading of some of the proponents of the drug and even some outreach sent to me by earlier emails from interested parties, has been that there has been no communication providing any information regarding possible significant side effects and risks of the drug.  For me, that is an important question as to why not.

J.

MN Chickadee

I am very disappointed by this; it looks pretty obviously like doing the bidding of big pharma so as to continue to get money from them. The AA hasn't addressed the safety concerns at all, and are ignoring the fact that there isn't great evidence it even helps. I suppose not all that surprising though. This is what happens when so much money could be made on a treatment. Plenty of greed to go around I guess.

Michael Ellenbogen

Sorry folks.

Moments ago, CMS released its final NCD ahead of the Monday deadline. 

The press release is here: https://www.cms.gov/newsroom/press-releases/cms-finalizes-medicare-coverage-policy-monoclonal-antibodies-directed-against-amyloid-treatment.

The full decision memo is here: https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=305.

Crushed

PRETTY FAIR NEWS STORY FROM STAT

 Medicare finalizes its restrictions on new Alzheimer’s drug, despite pressure from drugmakers

 

• 
  

By Rachel Cohrs April 7, 2022

  

WASHINGTON — Medicare on Thursday finalized its plan to restrict coverage for the controversial, pricey Alzheimer’s drug Aduhelm to patients participating in clinical trials.

The decision marks the end of an intense pressure campaign from drugmakers and some patient groups who wanted Medicare to reverse its initial proposal and pay for the drug for more patients. As clinical trials are usually run out of major medical centers, the decision will likely mean some interested patients won’t be able to access the drug. However, Medicare isn’t explicitly requiring that patients be treated at hospital-based clinics like the initial proposal.

The decision has implications beyond Aduhelm’s manufacturer, Biogen, as well. The coverage decision is not specific to Aduhelm, and applies to all drugs in the class, including a forthcoming treatment that Eli Lilly has begun to submit for FDA approval.

But in a major change from the initial proposal, Medicare officials created a sort of shortcut path for drugs that, unlike Aduhelm, demonstrate a clinical benefit for patients before they are approved. Medicare will cover those medicines for a broader group of patients.

They would still need to collect some data, but the possible design of the studies is much more flexible — a significant win for Lilly.

"This long-term pathway is meant to be nimble and respond to any new drugs in this class that are in the pipeline and demonstrate clinical benefits,” Lee Fleisher, Medicare’s Chief Medical Officer, told reporters.

Since the Food and Drug Administration approved Aduhelm last summer, doctors and scientists have raised questions about whether it actually works, government watchdogs have begun investigating whether the FDA followed proper procedure to approve it, and policy experts have questioned whether it is effective enough to justify its hefty price tag.

Medicare officials even hiked the entire program’s premiums to anticipate a potential flood of patients taking the pricey medication. But the new restrictions mean the drug will put less of a financial burden on the Medicare program. Health secretary Xavier Becerra said he soon plans to make a decision on whether to lower Medicare premiums for older adults after Medicare’s coverage decision for Aduhelm.

Aduhelm’s limited coverage policy is unprecedented, as Medicare almost always covers drugs if the FDA approves them. Aduhelm has been different because the agency approved the treatment without a guarantee that patients actually will see slower cognitive decline. The process that led to the drug’s approval is the subject of multiple investigations, following STAT’s reporting that Biogen had an extensive back-channel relationship with the FDA.

The Aduhelm coverage decision highlights a stark power struggle between Medicare and the FDA over Americans’ access to Aduhelm, but Medicare officials did give the FDA a major concession. The structure and set-up of the clinical trials Medicare is asking for will be overseen by the FDA or the National Institutes of Health, not Medicare itself.

Medicare will also limit those who can get the drug to people who have mild forms of cognitive impairment or mild dementia, and who have amyloid plaques, the proteins Aduhelm is designed to target, in their brain. The patient population is narrower than the one the FDA approved the drug to treat, as the FDA did not require proof of amyloid plaques. In a change from the initial proposal, Medicare chose to allow patients with other medical conditions, like Down syndrome, to participate in the trials as well.

The narrow coverage policy is a major blow to Biogen, which had hoped that access to the Medicare patient market could invigorate the drug’s meager sales.

The controversial tool that Medicare used to cover Aduhelm is called a “Coverage with Evidence Development.” It’s possible that Biogen or other drug makers could sue Medicare over the decision by arguing Medicare doesn’t have legal authority to require more studies to prove companies’ drugs benefit patients, said Sean Tunis, a principal at Rubix Health who helped develop the CED process during his tenure at the Centers for Medicare and Medicaid Services.

“In some ways the CED process hasn’t been challenged before in any way, because it wasn’t to anyone’s benefit,” Tunis said. Generally, CED tools have been used to regulate coverage of new indications of drugs or devices that wouldn’t have been covered otherwise.

Biogen did not immediately issue a statement on the coverage decision.

While many Americans with Alzheimer’s disease are also Medicare beneficiaries, the decision could have even broader implications, since most major insurers follow the federal government’s lead when it comes to setting their own policies for covering medicines.

Jo C.

Really remains difficult in various ways.  The day will eventually come when there will be clear cut benefits from such a drug.    It is complex as the disease itself is very complex on various levels.

The Medicare premium increase was harsh for some; it went up about $22/month.  In one year, for one person, that increase cost came to $246.  For a married couple, the annual increase means $528/year.  That is a significant increase mostly based on the cost of Aduhelm, even though certainly not all Medicare insured persons would have been using Aduhelm; it is a financial burden carried by all.

https://www.yahoo.com/news/medicare-weighs-premium-cut-limiting-221417203.html

Do hope that Becerra does the right thing and rolls back the increased cost of the premium since the entire Aduhelm situation has changed.

Had to slightly amend my prior Post as I did not intend for it to sound as though I was referring only to one or a couple of groups pushing for the Medicare approval of the drug despite costs. That was not my intention.

J.

Michael Ellenbogen

FYI

1.  Medicare has adopted, without only minor amendment, its January 2022 proposed non-coverage decision.  Under the Final National Coverage Determination, CMS will not cover Aduhelm on any other monoclonal antibody (mAB) therapies in the future unless they are administered as part of a CMS-approved clinical trial.

 

2.  Under CMS’ final Medicare coverage policy, all FDA-approved monoclonal antibody (mAB) therapies will require “coverage with evidence development” (CED). CMS now has set up two different types of clinical trials it will require, depending on how the drug was approved at the FDA (this is the new part):

 

a.  For drugs such as Aduhelm that were approved under FDA’s “accelerated approval” pathway (meaning the drug was proven effective against a surrogate endpoint, but was not yet proven to have a clinically meaningful impact on health), CMS will only provide coverage for a limited number of Alzheimer’s patients who are required to enroll in a randomized research studies. Such studies will take years to complete and patients will have to risk getting a placebo. Most of the mAB products being brought to market, including Aduhelm, have used the “accelerated approval” pathway to demonstrate that they reduce amyloid plaque in the brain. CMS agrees that these drugs do exactly that, but CMS is rejecting the conclusion (known as the amyloid hypothesis) that reducing amyloid plaque will slow the decline in cognition and function. Thus, CMS will require further clinical randomized control clinical trials (with placebos) to demonstrate that Aduhelm and any other accelerated approval drugs demonstrate a decline in cognition and function;

 

b.  For drugs approved under FDA’s regular pathway (in other words, the drugs show a meaningful change in a clinical endpoint like slowing the decline in cognition and function), CMS will still require clinical trials, although these do not have to be randomized control trials, or involve placebos. Instead, patient registries and similar other studies may be accepted.

 

3.  The result of the CMS decision is that millions of patients will not have access to Aduhelm or any of the other mAB drugs to be developed, as only a few thousand (or, possible, a few tens of thousands) in the clinical trials will have Medicare coverage. Those left outside the trials will be not be covered and, in cases where they are able to access the therapy, they will have to pay all costs out of pocket. Further, the manufacturers that were planning on using the FDA “accelerated approval” pathway (which were a majority of the manufacturers working on mABs) will now have to restructure their clinical trial programs, delaying FDA approval even longer and restricting access to those patients who can find a provider participating in a CMS-approved clinical registry.  

 

4.  There are some fundamental policy shifts in the CMS announcement, including its rejection of the FDA’s accelerated approval pathway created by Congress 20 years ago (which has been very successful for 67 other CMS-covered drugs), and even for the entire FDA approval process itself.  CMS has now openly stated that FDA approval is no longer enough for CMS, and that CMS will now require additional clinical trials based solely on Medicare beneficiaries outside of well controlled clinical trial environments before it will extend coverage.  This is chilling indeed.

 

Thanks,

David

 

–––

David J. Farber

Jo C.

I have already provided this information in a separate free standing Thread of its own, but in the interest of keeping our knowledge expanded, it is a relevant part of this Thread.   It is important as 90% of people with Down Syndrome will develop Alzheimer's Disease, often in their 40's and 50's; some onsets have been in the 30's.  The extra chromosome that causes Down Syndrome evidently also causes the early and rapidly flourishing of amyloid plaques in the brain quite  robustly.  Much to learn and much to think about. 

https://www.yahoo.com/news/people-down-syndrome-longer-life-102915167.html

J.

Michael Ellenbogen

These are the folks that will be hurt by this.

Lane Simonian

The critical findings of the FDA statistician (which the FDA but not Medicare chose to ignore) were the following:

1.  There is no correlation between the removal of amyloid plaques and changes in cognition at the highest dose of aducanumab/Aduhelm.  If you want to treat amyloid plaques, Aduhelm is a good drug, if you want to treat Alzheimer's disease it is not.

2.  Non-APOE4 carriers showed no difference between those on placebo in regards to the rate of cognitive decline.

3. APOE4 carriers saw some very modest slowing down in the progression of the disease, but with the risk for brain bleeds and brain swelling.

So far, all the other anti-amyloid drugs have shown a similar pattern of results.  One of them-- ALZ-801--does not have serious side effects because it blocks the production of amyloid rather than remove it. 

One drug candidate--Anavex 2-73/blarcamesine--helped stabilize cognition for 18 months and panax ginseng helped stabilize Alzheimer's disease for two years (in open label trials which do have limitations).  These are primarily antioxidant medicines and only secondarily anti-amyloid medications.  This is where the focus should be on now. 

Crushed

Michael Ellenbogen wrote:

FYI

 

1.  Medicare has adopted, without only minor amendment, its January 2022 proposed non-coverage decision.  Under the Final National Coverage Determination, CMS will not cover Aduhelm on any other monoclonal antibody (mAB) therapies in the future unless they are administered as part of a CMS-approved clinical trial. 

  

2.  Under CMS’ final Medicare coverage policy, all FDA-approved monoclonal antibody (mAB) therapies will require “coverage with evidence development” (CED). CMS now has set up two different types of clinical trials it will require, depending on how the drug was approved at the FDA (this is the new part): 

  

a.  For drugs such as Aduhelm that were approved under FDA’s “accelerated approval” pathway (meaning the drug was proven effective against a surrogate endpoint, but was not yet proven to have a clinically meaningful impact on health)......

   b.  For drugs approved under FDA’s regular pathway (in other words, the drugs show a meaningful change in a clinical endpoint like slowing the decline in cognition and function), CMS will still require clinical trials, although these do not have to be randomized control trials, or involve placebos. Instead, patient registries and similar other studies may be accepted.  

David J. Farber 

this is called good science. FDA went off the rails when it approved "surrogate endpoints" that had little or no scientific support

In technical safety regulation we use "surrogate endpoints" all the time  but we back them with an aggressive post hoc regulatory system.  Driving tests for example are surrogate  endpoints but we also watch drivers and take away licenses.

In the FDA surrogate wonderland the manufacturers of useless drugs get to keep all the profits !!  There is no downside to getting a useless drug approved.  Imagine for a moment they had to escrow the profits until they proved clinical success, That would make the profits depend on clinical success not merely conning the regulator 
 
Boeing conned the regulator but forfeited a ton of money on 737 MAX.  
Drug companies have a regulatory paradise paid for by ordinary taxpayers
  

Also note that Medicare premiums is a regressive tax system that the very wealthy can opt out of

  

 

  
 
 
 
 
 

Crushed

Michael Ellenbogen wrote:

These are the folks that will be hurt by this.

You are assuming that the drug works

"Firstly, the committee that reviewed the drug was not informed that the accelerated approval pathway was being considered for approval. "

FDA  therefore got no expert input on the surrogate marker

 That tells you the FDA approval was irregular

 If they had listened to experts they would have heard a lot of criticism 

  
 
   https://www.science.org/content/article/alzheimer-s-drug-approved-despite-doubts-about-effectiveness

 

https://icer.org/news-insights/press-releases/in-revised-evidence-report-icer-confirms-judgment-that-evidence-is-insufficient-to-demonstrate-net-health-benefit-of-aducanumab-for-patients-with-alzheimers-disease/

 

https://dig.pharmacy.uic.edu/faqs/2021-2/october-2021-faqs/what-is-the-clinical-evidence-supporting-and-controversy-surrounding-the-use-of-aducanumab-aduhelm-tm-for-alzheimer-disease/

Michael Ellenbogen

WWhile  you may be smart I am on calls with at least 15 or more lawyers  who disagree with you.  So collectively I believe them. Sorry.

Crushed

Michael Ellenbogen wrote:

WWhile  you may be smart I am on calls with at least 15 or more lawyers  who disagree with you.  So collectively I believe them. Sorry.

I am well known for the quote

Lawyers can make anything legal only Doctors , scientists and Engineers can make it safe  
 
lawyers conning a regulator is no great trick

Tell me you when you  have 15 top  independent neuroscientists  and Neurologists and i'm interested 

  Neurologists' Group Issues Guidance to Families on Controversial Alzheimer's Drug "Aducanumab is not a cure for Alzheimer's disease, yet since it has been approved by the [U.S. Food and Drug Administration], patients are asking their doctors if this is an option for them," said statement author Dr. Winston Chiong, an associate professor at the University of California San Francisco and member of the AAN's Ethics, Law and Humanities Committee.

"This is a high-cost drug that was approved by the FDA without convincing evidence of benefits and with known harms, so the purpose of this position statement is to offer ethical guidance on how neurologists can help patients make informed decisions about this treatment," Chiong said in an AAN news release.

The U.S. Food and Drug Administration approved aducanumab (brand name: Aduhelm) based on two studies that were both stopped early because the drug showed no benefits for patients. The statement explained that a later analysis of data from one of those studies suggested a small benefit, while the other still showed no benefit.

The statement noted that while aducanumab reduces the beta-amyloid plaques in the brain that are markers of Alzheimer's, it's unclear whether that provides any meaningful benefits to patients.

There isn't sufficient evidence to offer the drug to patients with moderate or advanced dementia, or to those without evidence of beta-amyloid in the brain, according to the position statement published Nov. 17 in the journal Neurology.

It also said the drug carries a risk of brain inflammation and brain bleeds, which occurred in a third of patients in the studies who received the dose approved by the FDA.

The statement said neurologists must inform patients and families about the drug's potential risks of and the need for more frequent monitoring with MRI scans.

Another issue is the lack of racial and ethnic diversity in the clinical trials of aducanumab. Patients in racial and ethnic minorities need to be told about the lack of safety and effectiveness data for them, the statement said.

In addition, it warned that pricing and insurance coverage of the drug may cause financial harm to patients and their families.

Aducanumab is priced at $56,000 a year. But the costs of infusing the drug, repeated imaging and medical management may push annual costs to more than $100,000. Medicare generally covers 80%, so patients and families must be told that the full cost of treatment may not be covered, the statement advised.

The statement said another concern is that availability of aducanumab may lead to lower patient enrollment in clinical trials of more effective treatments.