More on FDA approval of Aducanumab
What a Bad Day Science Had
June 7, 2021, was a bad day for science. That was the day the U.S. Food and Drug Administration approved aducanumab for the treatment of Alzheimer’s disease, even though a committee of its own selected experts recommended strongly against approval. The committee found that studies failed to prove the medicine works, or that its benefits outweigh side effects, which include swelling and bleeding in the brain. In a break from precedent, the FDA did not accept its committee’s recommendation, but delayed its decision for months, culminating in an announcement of approval.
How, you might ask, could this happen? This is in a sense a failure of scientific integrity, not in the sense of bribery or overt cheating, but in the failure to honor the scientific method and to acknowledge when research fails. The FDA’s website states, “FDA has determined that there is substantial evidence that [Aducanumab] reduces amyloid beta plaques in the brain and that the reduction in these plaques is reasonably likely to predict important benefits to patients.” The first part of the sentence is indisputably true – this drug does reduce the amyloid plaques long associated with Alzheimer’s disease. The second part of the sentence – that reducing amyloid is “likely” or “expected” to help patients — is repeated three times in FDA’s press release with slight variations. Despite this insistence, this claim is not about evidence but about hope, a hope that has been proved wrong repeatedly in multiple large studies, involving thousands of patients and hundreds of millions of dollars over 15 years.
https://www.thehastingscenter.org/what-a-bad-day-science-had/
Comments
-
Thank you for the article. Very disturbing.0
-
Two members of a Food and Drug Administration advisory panel resigned this week after the agency’s contentious decision to approve an Alzheimer’s drug over the objections of its outside advisers.
David S. Knopman, a neurologist at the Mayo Clinic, said Wednesday in an email to The Washington Post that he did not “wish to be part of a sham process” that ultimately resulted in the agency’s approval Monday of Biogen’s Aduhelm, also known as aducanumab.
He also shared the email he sent to FDA officials saying that he was resigning immediately. He told the officials: “The whole saga of the approval of aducanumab … made a mockery of the [advisory] committee’s consultative process. While I realize that the committee is advisory, the approval of aducanumab appears [to] have been foreordained.”
Earlier this week, Joel S. Perlmutter, a neurologist at Washington University in St. Louis, resigned from the committee, according to the trade publications Stat News and the Pink Sheet. Perlmutter told Stat in an email that he quit “due to this ruling by the FDA without further discussion with our advisory committee.”
https://www.washingtonpost.com/health/2021/06/09/alzheimers-drug-controversy/
0 -
Re Aduhelm
Finally a FDA approved AD medicine@a hefty price tag of $ 3400. Per treatment, who can afford to buy? Who is going to help AD patients buy it? Medicate? Aarp?
Any thoughts? Will the dr even prescribe it?
0 -
I think its $56,000 a year. From what I have herd that is much cheaper then any drug would be for dementia. I had heard it can be as high as a million if
It definitely can slow it down or if a cure even higher. I know people who are working on reducing the price or trying to find other ways. I do know Biogen will be giving it to those who cannot afford it for free or discounted price. Not sure which. All of this is still being worked out.
0 -
"The recommended maintenance dosage is 10 mg/kg administered as an intravenous infusion over approximately one hour every four weeks. (2.1) • Obtain a recent (within one year) brain MRI prior to initiating treatment."
"Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s)."
The above is from the prescribing guidelines for aducanumab from the FDA. Below is a link to the FDA guidelines.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761178s000lbl.pdf
These are announcements about aducanumab from the Alzheimer's Association:
1.
2.
I believe that since aducanumab is approved by the FDA, so if there is a confirmed diagnosis of dementia based on an MRI, Medicare will pay 80%. Usually Medicare does not approve the stated cost, but something less, 25-30% usually.
Since the aducanumab infusions (monoclonal antibody drugs end in 'mab' which indicates 'monoclonal antibody') are FDA approved they will fall under part B (hospitalization, etc.) and are not categorized as a drug, by the way, but a therapy. I think a strong case can be made to any private medical insurance company for coverage if your LO is not on Medicare.
Biogen says it will work with any family to insure that aducanumab will be affordable. The cost is $56,000/year.
I have an Immune disorder and every month a nurse comes to infuse me with 35 gm IgG, which is charged at $15,000 per infusion ($195,000/year). Medicare, of course, approves about 30% of that amount, and then pays only 80% of the approved amount.. I am responsible for 20%. I have a supplemental plan which pays all that Medicare doesn't cover. Medicare also pays for the nurse to come to my house.
I have had this infusion every 4 months for 8 years. Each infusions takes 4 hours. I will have this infusion every 4 months for the rest of my life. The diagnostic requirements for eligibility for my treatment, which require donations from up to 10,000 donors for each infusion, are very demanding.
In 2018 my DH had a treatment for his cancer (CLL) with a monoclonal antibody, 6 monthly 4 hour infusions at $50,000 EACH! And Medicare approved all of the $50,000 for each treatment! I'd NEVER known Medicare to approve 100% of anything. Fortunately our supplement covered the incredible 20%: $10,000.
My DH's cancer is still in Total Remission 3 years after that treatment! The 6 infusions would have cost us $300,000, not including the cost of the administration of the drug.
I hope this information helps.
Elaine
0 -
Thanks to all of you for sharing information.
I think Biogen's ability to charge this amount will be short. Eli Lilly is working on a drug that produces similar results (donanemab). This will provide competition at least.
There are a number of companies working on drugs that should be more effective than Aduhelm. The one with the best chance of success in my opinion is Anavex 2-73 (blarcamesine). The company should have phase 3 trial results by next year or early 2023.
Biogen's drug was only studied in very early stage Alzheimer's patients. I would be surprised if many physicians or insurance companies approved the use of Aduhelm for anyone with moderate to severe Alzheimer's disease.
Other anti-amyloid drugs provide only a modest slowing down of the disease in ApoE4 carriers (they provide essentially no benefit for non-ApoE4 carriers). One of these drugs--Alz801--produces no significant side effects in ApoE4 carriers unlike Aduhelm which can produce brain-swelling and micro-bleeds.
Despite FDA approval, this was not an overwhelming victory for Biogen and it certainly was not an overwhelming victory for those with Alzheimer's disease.
0 -
Infusion??? That sounds difficult for a person with dementia!!!!0
-
Taking off my PV cap.
I've read what Michael read, $56,000 per year. That simply isn't a feasible for most of us. What concerns me - and has from DH's diagnosis - is the age requirement. For this medication it is for 'early onset' of 65 yrs old or older. DH's diagnosis was when he was 54. He's not 65 for several years.
To me - early on set - needs a new definition. Research for folks under 60 years old. As the baby boomers age more and more will fall into this category. Even some clinical studies have an age minimum of 65.
I keep expressing to anyone whom will listen that this disease doesn't need to have an age limit. Once diagnosed the same medications, etc should be available to everyone.
Climbing off my soap box and putting my PV cap back on.
eagle
0 -
Montelukast, a drug that reduces innate immune system caused inflammation, costs less than 20 dollars for a box of 30. I take one 10 mg tablet three times a day, which means that I take three boxes a month, which costs less than 60 dollars a month. I have been taking this drug for over five years and my initial extreme mental fatigue has completely gone.
Meanwhile Emory is about to quietly resume its montelukast/Alzheimers clinical trial after a pause because of the covid pandemic. There are no promotions coming from billion dollar pharmaceutical giants or news flashes coming from stock market watchers. Emory is quietly moving forward on this trial, which Emory is paying for itself. Hopefully we will see results in 2022.
I think when the results are in, a cheap generic will prove far more effective and safer than Aducanumab, which may not be effective at all.
0 -
Montelukast, a drug that reduces innate immune system caused inflammation, costs less than 20 dollars for a box of 30. I take one 10 mg tablet three times a day, which means that I take three boxes a month, which costs less than 60 dollars a month. I have been taking this drug for over five years and my initial extreme mental fatigue has completely gone up to now.
Meanwhile Emory is about to quietly resume its montelukast/Alzheimers clinical trial after a pause because of the covid pandemic. There are no promotions coming from billion dollar pharmaceutical giants or news flashes coming from stock market watchers. Emory is quietly moving forward on this trial, which Emory is paying for itself. Hopefully we will see results in 2022.
I think when the results are in, a cheap generic will prove far more effective and safer than Aducanumab, which may not be effective at all.
0 -
Montelukast is a scientifically worthwhile crap shoot. Its nasty side effects are in the area of mental health, which tends to support some kind of neurological operation
0 -
Since u have been taking Montelukast for 5 years, is your memory better? DH started taking this 10 mg daily one month ago. He has mid AD. I am waiting to see how long snd how much improves memory.I wonder if increasing dose to 20 mg will help? DH has Diabetes, heart and some kidney issues.
Since it’s a allergy medication, it was difficult to get a prescription for AD
Thanks
0 -
I have had infusions as part of a medical trial for dementia. They lasted about 2 hours and no to bad. If I knew that could make me better or at least stay at where I am I would gladly take it for the rest of my life.
As far as the Biogen approval I am a bit concerned my self as to how it got approved. I also wanted them to get approval but only the right way with real scientific backing. I don’t believe that happened here and this could be a dangerous road for other drugs.
0 -
sunshine5 wrote:Please check back with us and let us know how your DH makes out.
Since u have been taking Montelukast for 5 years, is your memory better? DH started taking this 10 mg daily one month ago. He has mid AD. I am waiting to see how long snd how much improves memory.I wonder if increasing dose to 20 mg will help? DH has Diabetes, heart and some kidney issues.
Since it’s a allergy medication, it was difficult to get a prescription for AD
Thanks
0 -
Montelukast is a very safe drug for adults. Unfortunately the FDA ruled last year that montelukast must come with a black box warning. This was due to complaints about montelukast's psychiatric side effects in a small percentage of children taking this drug for asthma - side effects such as agitation, depression, and suicidal thoughts.
In Merck's FDA clinical trial application submitted more than 20 years ago, they stated that montelukast does not cross the blood brain barrier (BBB) to any significant degree, which was totally false. If the FDA had known the real facts, they would have more careful about approving this drug for children as an asthma drug.
A further problem is that Merck applied for once a day dosage for asthma. Montelukast has a short half life of 2 to 5 hours. Anti-inflammatory drugs given on a long term basis which can cross the BBB and have a short half life are usually given in multiple doses throughout the day. Giving this drug once a day leads to a peak level in the blood stream soon after taking to a very low non-theraputic level by the end of 24 hours. Large fluctuations in the amount of the drug crossing the BBB during a 24 hour period could lead to neuro side effects in many patients. Certainly if the FDA knew montelukast crossed the BBB, they would also have questions about once a day dosing.
I think that the Emory montelukast/Alzheimers trial will show that montelukast given to patients in multiple doses during the day is effective and safe.
0 -
Sunshine, I was not having a memory problem. What I was experiencing was extreme mental fatigue. I was getting enough sleep but I felt like I had not slept for two days. I have a degree in math but I was having difficulty solving simple algebra problems while tutoring kids in the neighborhood. I started by taking montelukast 10 mg once a day and was back to normal for about half a day. I soon started 10 mg twice a day and was completely back to normal all the time. Later I started taking 10 mg three times a day.
If your doctor will only prescribe 10 mg per day, maybe you can talk him into prescribing 5 mg in the morning and 5 mg in the evening. It's still 10 mg a day but the amount of the drug in the bloodstream would not fluctuate so greatly. As for his memory, I don't know if it could improve, but maybe it could slow down his decline.
0 -
Larrytherunner wrote:
Montelukast is a very safe drug for adults. Unfortunately the FDA ruled last year that montelukast must come with a black box warning. This was due to complaints about montelukast's psychiatric side effects in a small percentage of children taking this drug for asthma - side effects such as agitation, depression, and suicidal thoughts.
This statement does not appear to be supported by the literature. The elderly are in fact a critical risk group and the risk is death by suicide
We identified 82 cases of completed suicide associated with montelukast, with many reporting the development of concomitant neuropsychiatric symptoms prior to the event. Forty-five cases were reported in patients older than 17 years, 19 cases were reported in those 17 years and younger, and 18 cases did not provide the age of the patient.
it goes on to say We also reviewed evidence from animal studies, which suggest montelukast could act directly on cells in the brain. Orally administered montelukast (10 mg/kg/day for 7 days) was detectable in brain tissue and cerebrospinal fluid in rats, providing evidence of its ability to cross the blood-brain barrier.1
The risk is particulalry striking in the Elderly
Background
In March 2020, the US Food and Drug Administration decided that the dangers related to neuropsychiatric events (NPEs) of montelukast, one of the leukotriene modifying agents (LTMAs), should be communicated through ‘boxed warning’. In case of NPEs, the prevalence has been the highest in elderly people. Because the characteristics of the elderly such as old age itself can act as risk factors. Therefore, an investigation on safety of LTMAs related to NPEs in elderly using LTMAs is needed.
Conclusion
This study suggests that elderly asthma patients prescribed LTMAs had a higher risk of NPEs than patients who were not treated with LTMAs. Therefore, clinicians should be aware of the potential risks of LTMAs.
https://asthmarp.biomedcentral.com/articles/10.1186/s40733-021-00070-4
0 -
Larry: when posting on this board or the clinical trials board, please preface any post by identifying that you are not a person with dementia. It is easy for newcomers or even regulars, to become confused about why you are posting on these boards.0
-
Marta, they can read Larry's profile. Larry has been very informative over the five years he has been posting.
Iris
0 -
Marta wrote:I just read Larry's profile and he said he does have dementia.Larry: when posting on this board or the clinical trials board, please preface any post by identifying that you are not a person with dementia. It is easy for newcomers or even regulars, to become confused about why you are posting on these boards.0
-
Elshack wrote:Marta wrote:I just read Larry's profile and he said he does have dementia.Larry: when posting on this board or the clinical trials board, please preface any post by identifying that you are not a person with dementia. It is easy for newcomers or even regulars, to become confused about why you are posting on these boards.
I don't think so. he states " I started thinking that this was the beginning of early Alzheimers."
Also FWIW I believe that the "boxed warning" will require a rereviw of any Montelukast study by the Emory IRB
0 -
In the column to the left of the profile, Larry states he has dementia.0
-
Thorough article explaining clearly the challenges and difficulties re this drug's unusual approval . . . three eminent professionals, (from Harvard, Mayo, and Johns Hopkins), quit the FDA Advisory Committee in response to what they felt was a breach of the approval dynamics and more . . . personally, I am not convinced . . . . but still . . . .
https://www.yahoo.com/news/controversy-over-fdas-approval-first-153412831.html
J.
0 -
Marta wrote:In the column to the left of the profile, Larry states he has dementia.
I realize that but Larry is not qualified to diagnose himself.
“Oh, life is a glorious cycle of song,
a medley of extemporanea,
And love is a thing that can never go wrong,
and I am Marie of Romania.”
Dorothy Parker0 -
I like this very much. Best wishes under very difficult circumstances to everyone here.
I almost feel guilty returning to the harsh reality of Aduhelm, but the more I dig into it the more frustrated I become. Aduhelm was approved without any limitations (other than having to conduct a confirmatory trial which may take up to nine years).
Here is a list of people the drug should not be prescribed for:
Individuals with moderate to severe Alzheimer's disease:
The drug was only tested for individuals with mild cognitive impairment to very early Alzheimer's disease. A drug cannot be approved when no clinical trial was performed for other stages of Alzheimer's disease.
Non-ApoE4 carriers
Neither trial produced any change in non-ApoE4 carriers at 78 weeks.
Did Only APOE4s Benefit? On the clinical outcome measures CDR-SB, MMSE, ADAS-Cog13, and ADCS-ADL (top to bottom), APOE4 carriers (red) fared better, while noncarriers (blue) did no better than the placebo group (dotted line).
https://www.alzforum.org/news/research-news/aducanumab-still-needs-prove-itself-researchers-say
https://www.fda.gov/media/143504/download
ApoE4 carriers with one copy of the gene
The slowing down in decline in this group was around twenty percent which is barely statiscially significant but not clinically significant.
ApoE4 carriers with two copies of the gene
This one is more difficult. Aduhelm can slow down the progression of very early Alzheimer's disease in this group by up to 40 percent which is clinically significant but it can also produce brain swelling and micro-bleeds. Another drug ALZ-801 is being developed that produces the same benefits but without the risks (although it may not be available until 2025).
How a drug that showed no clinical benefit even at the earliest stages of Alzheimer's disease for everyone except those with two copies of the ApoE4 gene got approved by the FDA for all Alzheimer's patients is beyond me. I think the government, private insurers, and caregivers are going to balk at paying $56,000 a year per person for a drug that requires infusions once every four weeks that has almost no benefit.
0 -
Marta, you are right that I don't have dementia. I got a tentative diagnoses of early stage age related dementia about 7 years ago, based on my symptoms of cognitive decline as related to the doctor, the fact that my mother was in the middle stages of Alzheimers, my age and the fact that the doctor ran a battery of tests and eliminated every other cause he could think of. I saw a doctor who worked in the one of the regional hospitals in Ghana in the neurology department. I'm sure if I had been given a written test, I could have passed because it is extremely easy and I have always done well on tests. All I know is that I had a big cognitive decline over that period, and I got back to normal very quickly after starting montelukast.
I believe the reason for the decline was related to neuro-inflammation, because montelukast is an immune system anti-inflammatory drug and I got back to normal after taking it. We will have to wait for the Emory clinical trial to get a better understanding of this treatment.
I won't continue to say that I had dementia but that I will say that I had about two years of extreme mental fatigue and cognitive decline before I started taking montelukast.
0 -
So, would you edit your profile to take out the statement that you have dementia?
And, I am so very glad you don’t have dementia.
Thank you for your Government Service. My adopted father was a GS in France, Germany, and Berlin, before the wall came down.
0 -
Thanks Larry.
I think the Emory research shows Montelukast to be effective in AD
I hope the dr prescribes the newly approved AD drug Aducanumab.
I see DH memory slowly getting worse to the point that he can’t remember how to find frequently called phone numbers on his iPhone and getting very agitated!
0 -
sunshine5 wrote:
Thanks Larry.
I think the Emory research shows Montelukast to be effective in AD
I hope the dr prescribes the newly approved AD drug Aducanumab.
I see DH memory slowly getting worse to the point that he can’t remember how to find frequently called phone numbers on his iPhone and getting very agitated!
The Emory study "emerald " has not been done. it is enrolling volunteers
https://alzheimers.emory.edu/research/clinical_trials/active-trials.html
No Study Results Posted on ClinicalTrials.gov for this StudyRecruitment Status : Recruiting Estimated Primary Completion Date : June 2022 Estimated Study Completion Date : June 2022
Aducanumab will be massively expensive and is risky and the data is very very very poor.
It's approved based on guesswork.
0 -
Patti Davis, author of "The Long Good-bye" suggests that Aduhelm might not be worth taking even if it works and even if it becomes affordable. Her argument is that the drug slows the progression of AD in the very early stages of dementia, thereby stalling the PWD at the most painful part of the disease. At that stage, "fear courses through them and they are grieving over the loss of who they once were." AD is unlike many other diseases in that the sufferer sometimes becomes more comfortable as the disease progresses. In short, she suggests some people might be happier accepting the existence of a fatal disease, grasping the nettle, and getting on with it since the drug is not a cure.
Davis doesn't say take it or not, she just thinks this is something we should consider.
0
Commonly Used Abbreviations
DH = Dear Husband
DW= Dear Wife, Darling Wife
LO = Loved One
ES = Early Stage
EO = Early Onset
FTD = Frontotemporal Dementia
VD = Vascular Dementia
MC = Memory Care
AL = Assisted Living
POA = Power of Attorney
Read more
Categories
- All Categories
- 469 Living With Alzheimer's or Dementia
- 237 I Am Living With Alzheimer's or Other Dementia
- 232 I Am Living With Younger Onset Alzheimer's
- 14K Supporting Someone Living with Dementia
- 5.2K I Am a Caregiver (General Topics)
- 6.8K Caring For a Spouse or Partner
- 1.8K Caring for a Parent
- 156 Caring Long Distance
- 104 Supporting Those Who Have Lost Someone
- 11 Discusiones en Español
- 2 Vivir con Alzheimer u Otra Demencia
- 1 Vivo con Alzheimer u Otra Demencia
- 1 Vivo con Alzheimer de Inicio Más Joven
- 9 Prestación de Cuidado
- 2 Soy Cuidador (Temas Generales)
- 6 Cuidar de un Padre
- 22 ALZConnected Resources
- View Discussions For People Living with Dementia
- View Discussions for Caregivers
- Discusiones en Español
- Browse All Discussions
- Dementia Resources
- 6 Account Assistance
- 16 Help