Personal Blog #35 … Biogen is Ending Sale of Aduhelm … 2/1/24

Yesterday, 1/31/24, Biogen announced that it will stop selling Aduhelm, its Alzheimer’s disease (AD) medication, by the end of this year.  When initial approval was given by the Food and Drug Administration (FDA) to market this medication in 2021, FDA required Biogen to conduct additional studies to prove the efficacy of this new drug.  Biogen announced yesterday that it is ending its study needed to obtain full approval from the FDA. 

Readers may remember reading my Personal Blog #23, posted on this site on 6/11/21 … “Letter to Acting FDA Commissioner re Aduhelm.”  In the first paragraph of that PB #23 column, I wrote: “On 6/7/21, the FDA approved the drug Aduhelm, Biogen’s aducanumab medication, an intravenous infusion to be administered monthly for people with Alzheimer’s disease.  Despite not one member of the FDA’s Advisory panel voting to approve this med, FDA approved its use anyway.  FDA determined that since Aduhelm helped clear some amyloid protein from the brain, it may be “expected to help slow dementia.”  However, Biogen’s own data do not support such a claim, and readers can read my Personal Blogs #11 and #12 to learn more about results of clinical trials with this drug.” 

I also wrote the following: “For many patients and caregivers, the high costs of AD medications present an economic hardship. Money spent on (ineffective) AD medications is money that might otherwise be spent on day care programs, companions, home health aides, or other services that would actually improve the quality of their lives.”

“I witnessed AD spouse caregivers having to spend life savings on AD meds.  Some had to sell their homes when placing spouses in assisted living or to cover costs of home health care aides.  Now even more will have to do so because of money needlessly spent on this latest bottle of hope you have approved.  Based upon data I have seen ... a difference of 0.39 on an 18 point scale of cognitive and functional ability ... I can understand why not one member of your 11 member Advisory panel of experts that evaluated the data for FDA voted for approval.”

“I am SO sorry that FDA has approved yet another costly "bottle of hope" that will now financially ruin the lives of more AD spouse survivors with virtually zero benefit to their loved ones.  This is just not fair to people with AD, and not fair to their eventually surviving spouses.”

I also shared an email correspondence I had with Dr. Janet Woodcock, then acting FDA Commissioner.  In one email I had written, “My gripe is that there is no clear evidence that this med will actually slow cognitive decline in a meaningful way.  Unless and until Biogen can produce clear evidence that their medication does slow cognitive decline to a significant extent, it remains only an expensive bottle of hope.”

I also quoted one of several members of the FDA Advisory panel who resigned from the panel in protest, Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School.  Kesselheim said that FDA’s decision on Biogen “was probably the worst drug approval decision in recent U.S. history … based on the debatable premise that the drug’s effect on brain amyloid was likely to help patients with Alzheimer’s disease.”

In the last paragraph of PB#23, I noted my final comment to acting FDA Commissioner Woodcock re Aduhelm: “I want so much to see a new medication that will truly slow down the progression of the disease to allow a longer period of quality of life.  I want so much to see development of a new medication that will successfully treat if not cure AD.  (But) When an Advisory FDA panel has 11 experts and not even one of those experts votes to approve this medication, one has to wonder how something like this could happen.”

According to yesterday’s report by The Associated Press (AP), about 2,500 people worldwide are currently taking Aduhelm.  The AP report further stated, “Initially priced at $56,000 a year, analysts predicted it would quickly become a blockbuster that would generate billions for Biogen.  Medicare raised the premiums it charges for its coverage partially because of an expected influx of Aduhelm claims.  But doctors were hesitant to prescribe the IV drug, given weak evidence that it meaningfully improved Alzheimer’s patients lives.”

Although it comes as no surprise to me, I am deeply saddened to see yet another much hyped potential AD medication be declared a failure.  I have expressed my concerns about 2 other new AD meds targeting amyloid proteins (plaques) in the brain in Personal Blogs #28, #31 and #32.  These columns expressed my strong views on Lecanemab (now marketed as Leqembi), and Donanemab, a med that the FDA is expected to consider for approval within the next month or two. 

Given Biogen’s failure with Aduhelm, I can only reiterate what I wrote in last month’s PB #34.  Until science discovers exactly what causes AD … and as of today there is no definitive proof that AD is caused by the build-up of amyloid proteins in the brain … it will be extremely difficult if not impossible to develop a medication that can prevent AD or treat AD effectively.

 

 

 

 

Personal Blog #34 … Will 2024 Be the Year We Finally Discover the Cause(s) of Alzheimer’s Disease? … 1/14/24

I didn’t know much about Alzheimer’s back in 2007, but that was the year when I started searching the Internet for reasons to explain why, in my opinion, my wife was exhibiting worrisome behaviors.  Nobody else seemed to be noticing those behaviors, but I was seeing them more and more.  I continued worrying, I continued educating myself, and by early 2008 I was convinced that my wife was already dealing either with Mild Cognitive Impairment (MCI) or the early stages of Alzheimer’s disease (AD). 

Although my wife saw no reason to do so, I was able to convince her to see a neurologist after we returned from a particular trip in 2007.  During that trip, my wife exhibited many worrisome behaviors.  She was forgetting simple things (like our hotel room number or the names of our children and grandchildren), losing and misplacing things (leaving her sweater, coat, camera, and pocketbook in hotel rooms and restaurants) and was frequently disoriented when visiting sites in cities. 

My wife and I had recently entered our 60s and, like many friends our age, we were already starting to have those occasional “senior moments” when we’d forget something we knew well.  But my wife getting us lost on a regular basis was a major worrisome behavior.  I always got lost because I have no sense of direction, but I had always relied upon my wife’s “built-in GPS system” that, until that trip, had always guided us correctly wherever we were.  On that 2007 trip, however, even I knew she was repeatedly leading us in the wrong direction, we were frequently lost, and I, the one with no sense of direction, had to somehow lead us back to the correct location.

Throughout the rest of that year and in 2008, my wife’s doctors … first just our internist, and then the neurologist … saw no signs of MCI or AD.  They were both treating her first for stress, then for anxiety, and then for depression.  Throughout that time, I could not get my wife to agree to see another doctor for a second opinion, and each time I’d bring up that suggestion she would scream at me saying it was unnecessary.  Towards the end of 2008 and into early 2009, the neurologist suggested that my wife also be seen weekly by a clinical psychologist to help her with “coping mechanisms.”

At home I was regularly seeing new worrisome behaviors emerge, but none of my wife’s doctors observed these behaviors and all of her cognitive testing (MMSE tests, mostly) and brain scans seemed to be normal.  Despite what the doctors told me, I was now totally convinced that my wife was in the early stages of AD based upon all of my online reading from highly reputable governmental sites (such as NIA, NIH, and CDC), hospital sites (such as Mayo Clinic, Johns Hopkins, and Cleveland Clinic) and organizational sites (such as the Alzheimer’s Association, Fisher’s Center for Alzheimer’s Research Foundation, and UsAgainstAlzheimer’s).

In early 2009, feeling very frustrated that my wife was not properly diagnosed and was not being treated properly, I confronted the clinical psychologist.  I asked that if it were his wife being treated for more than a year for stress, anxiety, depression… and was actually getting worse … would he take his wife for a 2^nd opinion?  The psychologist said he had just spoken that morning with my wife’s neurologist.  I cut him off in mid-sentence, saying I had no faith in that neurologist.  I again repeated, would he take his wife for a 2^nd opinion?  The psychologist, now red-faced, said yes.  I turned to my wife and asked, “Now can I take you for a 2^nd opinion?”  She said “yes.”

Within a month my wife was seen by a geriatric psychiatrist affiliated with an Alzheimer’s Disease Research Center.  After just two lengthy visits and many hours of bloodwork, interviews, cognitive testing (not just the MMSE, but many tests), and new brain scans … and lengthy interviews of me to determine behaviors I was witnessing …  my wife was diagnosed with early onset AD.  Within a month my wife was taking Aricept, enrolled in a promising clinical trial, and my frustrations eased considerably because I now felt (in retrospect, naively so) that my wife was finally being treated effectively.

It has now been 15 years since my wife’s diagnosis in 2009.  What have we learned about the cause or causes of AD in those 15 years?  Sadly, the short answer is … not all that much.

Fifteen years ago I learned about amyloid-beta proteins (plaques) and tau proteins (tangles) and noted that most AD research money flowed into projects intended to definitively determine how one of both of those proteins were the cause(s) of AD.  Unfortunately, here we are in 2024 and we still haven’t conclusively determined if that is true, and at this stage many researchers are wondering if the presence of amyloid proteins may the results of AD rather than the cause.

Based upon a 2022 study at the University of Cincinnati, the chief neurologist and his research colleagues “hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing. The paradox is that so many of us accrue plaques in our brains as we age, and yet so few of us with plaques go on to develop dementia.” ¹

The latest statement from CDC, the Centers for Disease Control and Prevention, states the following: “Scientists do not yet fully understand what causes Alzheimer’s disease. There likely is not a single cause but rather several factors that can affect each person differently.” ² 

CDC does note some risk factors for AD  and several of those are listed on the CDC site.  Unfortunately, people have no control over the number one risk factor … age.  As we have long known, “Age is the best known risk factor for Alzheimer’s disease.”   All other risk factors noted by CDC are either ones we cannot control (e.g., family history) or statements with caveats such as, “a healthy life style may (my emphasis added) play a role in developing AD.” 2

The NIA, National Institute of Aging, notes the following on its site: “In recent years, scientists have made tremendous progress in better understanding Alzheimer’s and the momentum continues to grow. Still, scientists don’t yet fully understand what causes Alzheimer’s disease in most people.” ³  The NIA site suggests something similar to what is on the CDC site.  In its section, “What causes AD,” The NIA page has the following statement: “The causes probably (my emphasis added) include a combination of age-related changes in the brain, along with genetic, environmental, and lifestyle factors. ³

Similar non-emphatic statements can be found on just about any reputable site.  According to the Mayo Clinic, “The exact causes of Alzheimer's disease aren't fully understood … Scientists believe (my emphasis added) that for most people, Alzheimer's disease is caused by a combination of genetic, lifestyle and environmental factors that affect the brain over time.” ⁴

Organization websites, such at that of the Alzheimer’s Association, say something similar: “Researchers believe there isn't a single cause of Alzheimer's disease. It likely (my emphasis added) develops from multiple factors, such as genetics, lifestyle and environment. Scientists have identified factors that increase the risk of Alzheimer’s. While some risk factors — age, family history and heredity — can't be changed, emerging evidence suggests there may (my emphasis added) be other factors we can influence.” ⁵

So, whereas we have made some progress in learning about AD in these past 15 years, we still haven’t learned what causes AD.  It is extremely difficult to effectively prevent or treat a disease when we do not know the cause(s).  We are basically proceeding with common-sense advice that seems rational … that a healthy life style of eating nutritious foods, regularly exercising, avoiding brain injuries, etc. may (my emphasis added) prevent some (my emphasis added) people from developing AD.  But, as of today, we do not know that for sure.

It is too late for my wife, who died in 2016, and millions of others who have passed away directly because of AD or with AD as a major contributing factor.  Although continually listed among the top 10 causes of death in this country, the number of people dying with or because of AD is considered significantly greater than what is reported on death certificates.  According to the Alzheimer’s Association, “Death certificates for individuals with Alzheimer’s often list acute conditions such as pneumonia as the primary cause of death rather than Alzheimer’s … even though Alzheimer’s disease may well have caused the acute condition listed on the death certificate.” ⁶

When I received the death certificate from the nursing home after my wife’s death, I was shocked to note that AD was not mentioned as either the direct cause or as a contributing cause. ⁷   When I asked the nursing home doctor why, his response was that he couldn’t prove that AD was the cause.  When I asked why he didn’t even include AD as a contributing cause, he said he couldn’t prove that either. 

Therefore, 2016 CDC mortality statistics for deaths due to AD in the U.S. did not include my wife’s death.  On page 6 of its 2016 report on mortality rates, CDC listed AD as the 6^th leading cause of death in this country in 2016. ⁸   On page 62 of that same CDC report, the following statement appears: “Quality of mortality data is largely dependent on proper and thorough completion of death certificates by certifiers. Accuracy and completeness of information entered on death certificates can vary by state from year to year.” ⁸   One can only wonder how many thousands of deaths in this country due in whole or part to AD each year have not been reported accurately on death certificates.

I hope our government continues to increase funding for AD research in hopes of finding an effective means of prevention or cure.  In 2009, the NIH allocated $457 million for AD research. 9   I am very pleased to note that estimated NIH funding for AD research proposed for 2024 is approximately $3.5 billion. 10   Hopefully, increased federal spending will result in promising research and discovery.

Discovering a definitive way to prevent AD is the goal, but I’d be very happy if we can just learn how to more effectively treat this disease.  Recent medications approved by the FDA to help those with AD do not excite me.  In fact, if my wife were still alive, I doubt whether she or I would have wanted her to take any of these new medications. ¹¹   

But even if AD remains a death sentence with no cure, treatment that can enable people with AD to maintain and enjoy a high quality for life for 10, 15, or 20 years after diagnosis would be a wonderful advance. 

Maybe 2024 will be the year when this happens.

1.  Tedeschi, Tim. UC study: Decreased proteins, not amyloid plaques, tied to Alzheimer’s disease.  Accessed on January 14, 2024.  https://www.uc.edu/news/articles/2022/09/decreased-proteins-not-amyloid-plaques-tied-to-alzheimers.html

2.  Alzheimer’s Disease and Healthy Aging.  Centers for Disease Control and Prevention.  Accessed on January 14, 2024.  https://www.cdc.gov/aging/alzheimers-diseasedementia/aboutalzheimers.html#:~:text=Scientists%20do%20not%20yet%20fully,risk%20factor%20for%20Alzheimer's%20disease.

3.  What causes Alzheimer’s disease?  Accessed on January 14, 2024.    https://www.nia.nih.gov/health/alzheimers-and-dementia/alzheimers-disease-fact-sheet 

4.  Alzheimer’s disease.  Mayo Clinic.  Accessed on January 14, 2024.  https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447

5.  Causes and Risks for Alzheimer’s disease.  Alzheimer’s Association.  Accessed on January 14, 2024.  https://www.alz.org/alzheimers-dementia/what-is-alzheimers/causes-and-risk-factors

6. 2023 Alzheimer’s Disease Facts and Figures.  Alzheimer’s Association.  Accessed on January 14, 2024, p. 35.  https://www.alz.org/media/documents/alzheimers-facts-and-figures.pdf

7.  Vann, Allan S.  Reporting Deaths of Patients with Alzheimer’s.  Journal of the American Geriatrics Society.  December, 2016. 64:12, pp. 2419-2420.

8. Deaths: final data for 2016, July 26, 2018.  Centers for Disease Control and Prevention.  Accessed on January 14, 2024.  https://stacks.cdc.gov/view/cdc/57989

9.  Research Priority Setting, and Funding Allocations across Selected Diseases and Conditions.  National Institutes of Health.  Accessed on January 14, 2024.   https://www.gao.gov/assets/gao-14-246.pdf

10.  Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC).  NIH RePORT.  Accessed on January 14, 2024.  https://report.nih.gov/funding/categorical-spending#/

11.  Vann, AS. ”Reflections of An Alzheimer’s Spouse.”  Personal Blog columns # 28, 31, and 32 discuss recent medications approved by the FDA within the past 2 years.  https://allansvann.blogspot.com/

Personal Blog # 33 … Concerns About AD? Be Sure to See the Right Doctor! ... 10/10/23

 

Personal Blog # 33 … Concerns About AD?  Be Sure to See the Right Doctor!

A friend of mine recently told me about the problems she went through trying to obtain an accurate diagnosis for the causes of increasingly worsening gastrointestinal issues her daughter was facing.  Despite being seen and treated by her primary care doctor, an internist, a gastroenterologist, and numerous MDs in hospital ERs, her issues continued to worsen.  Why?  It turned out that for many years she was repeatedly misdiagnosed and given medications that were not helpful.  Conditions such as anemia, appendicitis, nervous stomach, stress, hemorrhoids, and ulcerative colitis are just some of the misdiagnoses given to people who actually have Crohn’s.

At a certain point, my friend’s daughter was seen by a gastroenterologist with experience diagnosing and treating patients with Crohn’s disease.  Once properly diagnosed and treated for Crohn’s disease, there was immediate improvement in her condition and ability to function more normally.

According to the Mayo Clinic website, “Crohn's disease is a type of inflammatory bowel disease (IBD). It causes swelling of the tissues (inflammation) in your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition.  Inflammation caused by Crohn's disease can involve different areas of the digestive tract in different people, most commonly the small intestine. This inflammation often spreads into the deeper layers of the bowel.  Crohn's disease can be both painful and debilitating, and sometimes may lead to life-threatening complications. There's no known cure for Crohn's disease, but therapies can greatly reduce its signs and symptoms and even bring about long-term remission and healing of inflammation. With treatment, many people with Crohn's disease are able to function well.  (https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304)

Doctors misdiagnosing various diseases is nothing new, and my friend’s daughter was fortunate to finally be with a doctor who correctly diagnosed and treated her condition.  However, there are steps one can take to help minimize chances of misdiagnoses.  By reading about some of the mistakes I made with my wife, some readers may be able to avoid similar mistakes with their loved ones when there are concerns about AD.

Readers of my articles and blog columns already know that my wife, who died in 2016 due to AD, had been misdiagnosed for several years.  When I first began to notice behavioral changes in my wife and grew increasingly concerned that those changes might be signs of AD, we discussed these changes with our primary care doctor.  That doctor administered an MMSE … Mini-Mental State Evaluation … a very common test used by doctors to screen for possible AD.  My wife aced the test with a perfect score.  Unfortunately, I didn’t know that the MMSE was never intended to be used to screen for possible AD because, among other reasons, it does not test higher order thinking skills.  Our doctor gave my wife a prescription to reduce stress and anxiety.

My mistake was thinking that all was well based upon that MMSE score.  Even though our family physician said he was not an expert in AD, he could not detect any problems that, in his opinion, would warrant any additional testing. 

Months later, and observing new and worsening behaviors that I now thought could possibly be signs of AD, we met with the most highly respected neurologist in my geographic area, chair of the neurology department at a large and well-respected hospital.  I was also quickly educating myself about AD by visiting various internet sites such as those of the NIH, Mayo Clinic, Johns Hopkins, and the Alzheimer’s Association.

I was maintaining weekly logs noting new or worsening behaviors that I felt were clear signs of Mild Cognitive Impairment (MCI), if not early signs of Alzheimer’s disease (AD).  During the next 12-18 months, at every visit with every doctor I shared my latest logs, but doctors dismissed my logs without comment … often not even bothering to take time to skim or read what I had written.  The neurologist treating my wife for stress, for anxiety, and depression then also had her meet weekly with a clinical psychologist. 

My mistake was thinking that any neurologist or clinical psychologist would be easily able to diagnose AD.  My wife’s neurologist, a specialist in other brain disorders, was not an expert in AD.  My wife’s psychologist was a specialist in treating anxiety disorders, not AD.  Signs of AD that were obvious to me were misinterpreted by them and her diagnosis remained stress, then anxiety, and then depression … not AD.  I shared what the neurologist and clinical psychologist were saying about my wife with our primary care doctor, telling him that what I was observing seemed to clearly indicate early stages of AD.  Our doctor said that, based upon the behaviors I was observing, it was possible that my wife was in early stages of AD … but he deferred to the opinion of the neurologist who had much more experience with brain issues.

My mistake was not being strong enough to challenge my wife who continued to resist going for a second opinion.  We “fought” over it, but invariably she’d adamantly argue that she didn’t need to see another doctor and I couldn’t force her to do so.  I backed down each time, but I should never have backed down.  My wife said that since our family doctor, the neurologist, and the clinical psychologist all agreed that her problems were due to stress, anxiety, and/or depression … not MCI  and certainly not AD … there was no need to get another opinion. 

I was only able to bring my wife for a second opinion after I decided to confront the psychologist in my wife’s presence after a particular session.  I asked if his wife was being treated for stress, anxiety, and/or depression … and if his wife not only was not improving but was actually getting worse … would he take his wife for a second opinion?  When he said, red-faced, that yes, he would do so, I turned to my wife and asked, “Now will you let me take you for a second opinion?”

I was not going to repeat my mistakes of the past.  I had already gathered information on three doctors whose entire practices were focused on diagnosing and treating people with AD.  Two were geriatric psychiatrists affiliated with an Alzheimer’s Disease Research Center (ADRC) and one was a neurologist at another major hospital.  I showed the information on all three doctors to my wife and she chose one of the two geriatric psychiatrists.  We made an appointment and when the doctor learned that I had been keeping weekly logs of her behaviors, he asked me to email copies of those logs prior to our visit.  We then had several email exchanges about those behaviors, and even before our first visit I felt that we were now finally seeing the right doctor! 

My wife’s initial 3+ hour evaluation included the MMSE but also many, many more tests. After just thirty minutes spent evaluating my wife, the geriatric psychiatrist said that my wife was definitely not suffering from stress, anxiety or depression.  He wanted her taken off all of those medications, saying that ”something is going on in her brain’s frontal lobe.”  One month after all of her testing was completed … extensive cognitive testing, blood work, brain scans, physical exams, etc. … I received a call from the ADRC that, after a team meeting discussing all of her test results, my wife was diagnosed with probable early onset AD.

What is my advice to people with concerns about possible signs of AD in their loved ones?  Don’t visit just any doctor.  See  only a doctor experienced in diagnosing and treating people with AD.  Not all brain doctors … not even specialists such as neurologists and geriatric psychiatrists … have enough experience with AD to diagnose it properly.  Make sure you see a doctor who can do this.

And one more thing, something that is very sad to note.  Not all ADRCs will even take the time to make an initial diagnosis for people with concerns about possible AD symptoms!  I only recently learned about a friend who felt that he may be experiencing early signs of AD.  He made an appointment to see a specialist at his local ADRC, but they refused to see him once they learned that he did not yet have “sufficient” testing by other doctors first … brain scans, blood work, etc.

I emailed the following question to the person in charge of ADRCs at the National Institutes of Health: “Can my friend simply go to an ADRC for a complete evaluation, or must he first undergo imaging and blood work and other tests by his internist or neurologist.  So far he is acing the MMSE given to him by his internist but yet he recognizes he is still having cognitive problems.  Can he just get a consult at his local ADRC?  Following is the response I received:

“Thank you for contacting the federal government’s National Institute on Aging (NIA), part of the National Institutes of Health (NIH) at the U.S. Department of Health and Human Services. NIA was established to improve the health and well-being of older adults through research. The institute conducts and supports basic, clinical, and social and behavioral research on aging and the special problems and needs of older adults and is the lead federal agency for Alzheimer’s disease and related dementias research.   We appreciate your interest in the services provided by the Alzheimer’s Disease Research Centers.  While NIA provides funding to these Centers, we are not involved in their daily operations. Therefore, you will need to contact each Center you are interested in to inquire about their protocols for diagnosis and testing.”

That response is very unfortunate.  An ADRC has precisely those experts who should be available to meet with people who have the earliest AD concerns.  Months of delay before seeing such experts will undoubtedly lead to increased mental anguish.  In addition, the need to undergo additional expensive testing is a critical issue if one does not have outstanding health insurance.  Conducting initial AD diagnoses are too important … they should be included in all ADRC mission statements and protocols for diagnosis and testing.

One more thing.  If you do go to a doctor who administers the MMSE and makes a decision solely based upon those test results, please go to another doctor … asap!  There are many evaluative instruments better than the MMSE to help in diagnosing MCI or AD.  No doctor should still be using the MMSE, a test created in 1975, as a sole test to diagnose probable AD.  A score of 24 or less on the MMSE is considered indicative of possible cognitive impairment.  As I noted, my wife continually got a score of 30 in her earliest years of undiagnosed AD.  But even two years after being diagnosed with AD at the ADRC, my wife was still scoring 25 or higher on the MMSE!  Enough said.

Personal Blog #32 … New AD Medication, Leqembi (Lecanemab), Receives FDA Approval and Coverage Under Medicare … 7/6/23

 

The U.S. Food and Drug administration (FDA) gave full approval today for Japanese drugmaker Eisai, and its American partner, Biogen, to market its latest medication, lecanemab (to be known as Leqembi) for those with mild Alzheimer’s disease (AD).  According to Teresa Buracchio, acting director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research, “Today's action is the first verification that a drug targeting the underlying disease process of Alzheimer's disease has shown clinical benefit in this devastating disease." 

Six months ago the FDA gave conditional approval for this new medication, but there was much debate in the medical community about the effectiveness demonstrated by its data.  Medicare said it would not pay for routine use of Leqembi until the FDA gave its full approval.  Today the FDA has given its full approval.  The FDA acknowledged that after an 18-month clinical trial with 1800 participants, results showed that those taking the new medication showed a significant difference on an 18-point scale measuring cognitive functioning and memory.  According to FDA, this study showed that Leqembi “slowed memory and cognitive decline by about 5 months for those receiving the medication as opposed to those receiving the placebo.”

A doctor quoted this afternoon in a USA Today article said, “This drug is not a cure. It doesn't stop people from getting worse, but it does measurably slow the progression of the disease. That might mean someone could have an extra six months to a year of being able to drive."  A doctor quoted this afternoon in The New York Times stated, “The risks are very vivid.  Within the first few months, you may have small bleeds or swelling in your brain, which may or may not be symptomatic and if not detected in time can cause disability.”

The FDA indicated that Leqembi will carry a” black-box warning” about possible side effects such as brain swelling and bleeding. The warning does not mention patients who are taking blood thinners, but Leqembi’s label says that “additional caution should be exercised” when considering whether to give blood thinners to Leqembi patients.  As also noted in The New York Times article, “Concerns about safety have been stoked by reports of deaths of three clinical trial participants who experienced brain swelling and brain bleeding, two of whom were being treated with blood thinners. Eisai has said it is unclear if Leqembi contributed to their deaths because the patients had complex medical issues.“

 

In my Personal Blog #28, I noted that ”17% of the patients taking this medication suffered cerebral micro and macro hemorrhages and superficial siderosis compared to 8.7% in the placebo group.”  I also shared my feelings in PB #28 about medications yielding “statistical differences,” noting that although statistically significant those differences might not result in “real world” differences.

This new IV medication is priced at about $26,500 for a year’s supply of injections that are to be given every 2 weeks and Medicare will now cover about 80% of its costs.  This still leaves patients with 20% of the cost, plus other related expenses for doctor visits, required scans, etc.  Personally, I’d prefer that Medicare spend its money more wisely than subsidizing patients taking this new medication.  And I think patients can better spend their money on support groups, saving for the future when home health aides or assisted living or nursing home facilities may be needed, or for other present expenses or future costs.

So what is my take on this FDA approval of Leqembi?  Whereas I am truly pleased that we now have a medication that has shown it may be able to slow cognitive decline and memory loss by up to 5 months in an 18-month period of real time, I don’t think my late wife would have considered taking such a medication.  Why?  Three reasons:

First, getting IV injections every 2 weeks for a year would have been a very stressful experience.  Just getting ready to go and driving to and from the doctor’s office to receive IV injections twice a month would have been stressful.  In addition, my wife always felt pain with injections, bled easily, and her skin turned all pretty colors whenever receiving a needle for any reason … possibly due to all the heavy-duty heart medications she took each day, including 325 mg of daily aspirin.  Even had my wife  started this medication, I don’t think she would have continued for too long. Those IV needles would have been painful as well as stressful.

A second reason is the side effects.  AD is serious enough as it is, a death sentence with no cure and the 100% certitude of worsening conditions.  Gaining a few additional months of time to continue leading a more “normal” life before cognitive and memory issues worsen even more would be wonderful … but what a heavy price if those side effects occurred.  Dealing with AD and heart disease was enough of a double whammy for my wife.  Possibly compounding that with brain swelling, bleeding, headaches, etc. due to this medication could have made her situation even worse than it already was

The final reason is the real world “effectiveness” of this new medication.  Study participants taking the medication showed a gain of less than one half of one point on testing … a statistically significant outcome, perhaps, but I question how much of a clinical difference that difference would have really made in my wife’s life or in mine.  As that doctor quoted in The New York Times noted with respect to the slowing of decline with Leqembi, “The benefits of slowing are subtle. You’re not going to experience the perception of changes in your cognition or function in the same amount of time.”  As I noted in PB #28, not all studies demonstrating results showing “statistical differences” in testing translate into meaningful and/or observable differences in the real world.

By the time my wife was in early stages of AD, our lives had already changed dramatically.  A few more months of slower decline would have been welcome, but would probably not have changed much about our daily lives.  Especially when one considers that the trade-off to perhaps gaining a few months of slower decline might have led to losing the quality of life we still had.  Slowing decline doesn’t mean ending it and we may not have even noticed that slowing.  The added stress of two more doctor visits each month, the pain and after-effects of IV needles, and possible additional pain or hospitalization due to severe side effects of this new medication could have easily lessened whatever quality of life we still had.

So what is my bottom line reaction to this FDA approval of Leqembi?  It is this:  Would I have loved my wife to have declined at a slower rate for a few more months in those early stages?  Of course.  Would I have loved to have taken more trips with her? Absolutely.  But worrying about the possibility of her having a serious brain hemorrhage or other serious side-effect while traveling away from home would have worried me too much to have taken that chance. In fact, I would have been worried every single day, whether at home or not, had she been taking this new medication.

I haven’t even mentioned another real word effect of this new medication … the demands place upon the care partner of having to bring the AD patient to and from doctor appointments.  Even in early stages, AD patients may need assistance in dressing, mobility, may object to going out in bad weather or going out at a certain time of day, etc.   In addition, many care partners of AD patients are still working when their loved ones are in early stages, and time demands of taking loved ones to two visits each month for IV injections could be an additional burden for them as well.

So whereas I am truly pleased to welcome a new medication to try to help those with AD, I would not have found Leqembi worth the risk. 

Personal Blog #31 … Donanemab, a Proposed New AD Medication … 5/8/23

 

I debated whether or not to even write this blog offering my opinion about donanemab.  Last week there was yet another big pharma announcement of clinical trial data for a new medication as an effective treatment for those in early stages of Alzheimer’s disease (AD) … donanemab.  No one wants more than I do to learn about new effective treatments for those in any stage of AD.  However, I have been disappointed too many times by big pharma companies releasing announcements of positive clinical trial results without simultaneous disclosure of all supporting data and peer review commentary.  Early announcements of rosy results have too often overplayed the positive effects of new medications and too often downplayed serious negative side effects.  I fear that donanemab is just the latest AD medication that a big pharma company has touted as having promising results that are “statistically” significant but not really “clinically” significant, and with extremely dangerous side effects.  (Please see PB # 28, posted on 10/4/22, about my serious doubts about the “significant” published results and dangerous negative side effects of lecanemab (now sold under the brand name, Leqembi), last year’s new AD medication from Eisai and Biogen.  In that blog I also discuss how statistically significant differences in AD testing for new meds may be totally insignificant and meaningless with respect to functioning in the real world.)

According to an article published in Nature on May 4, “For the second time, an experimental drug has been shown to reduce the cognitive decline associated with Alzheimer’s disease. On May 3, pharmaceutical company Eli Lilly announced in a press release that its monoclonal antibody donanemab slowed mental decline by 35% for some participants in a 1,736-person trial — a rate comparable to that for competitor drug lecanemab.”  Lilly said it intends to seek FDA approval within the next month or two, will issue further results at a major AD conference in July, and seek publication of its data in a forthcoming peer reviewed journal.

Early reactions to this announcement have been mixed.  According to that same Nature article, “Researchers warn that until the full results are published, questions remain as to the drug’s clinical usefulness, as well as whether the modest benefit outweighs the risk of harmful side effects.  Some researchers who have reviewed the limited data released to date are doubtful of its effectiveness.”  Quoting Dr. Marsel Mesulam, a neurologist at Northwestern University, “The results that are described are extremely significant and impressive, but clinically their significance is doubtful.”

As reported in the May 3 NY Times article about donanemab, “24 percent of patients had the side effect of brain swelling and bleeding, and 6 percent had symptoms like dizziness, headache or fainting. Three patients in the Lilly trial died.  The company reported that two to three out of 10 patients taking donanemab progressed (to worsening stages of AD) over the next 18 months, compared to the expected three to four patients taking a placebo.” Lilly said that people with mild Alzheimer’s who received donanemab “showed 35% less clinical decline over 18 months than did those who received a placebo, and 40% less decline in their ability to perform daily tasks.”

According to the NY Times piece, Dr. Ronald Petersen, Mayo Clinic’s director of the Alzheimer’s Disease Research Center, said that “the donanemab results were modest but meaningful adding that  “patients and their families must be counseled about a dire side effect of donanemab - a risk of brain swelling that can result in death.”  Dr. Samuel Gandy, professor of Alzheimer’s disease research at Mount Sinai, noted that whereas the results for both lecanemab and donanemab were reported to be statistically meaningful, they have “only modest clinical benefit.” 

In an article about donanemab published in Science on May 3, the author wrote: “We cannot be sure that this drug will actually make a difference in the real-world care of patients with Alzheimer’s - not yet, anyway. This point is completely avoided in the Lilly press release, but it is nonetheless real and we will be hearing more about it from clinicians - well, if you listen closely above all the noise, that is.” Also noted is how the negative side effects in the donanemab trial were worse than those in the lecanemab trial.  For lecanemab, “the reported rates of ARIA-E and ARIA-H (measures of brain bleeds) were 13% and 17% of the trial participants, and the rates in this new donanemab trial were noticeably higher: 24% and 31%.”  That same article quoted a tweet from Dr. Robert Howard, a psychiatrist at University College London who has tested treatments for dementia.  Howard tweeted, “Looks as dangerous as lecanemab.”

I remain very skeptical while awaiting full data and peer review of results from Lilly’s new proposed medication, donanemab … and for the same reasons as noted in my PB #28 about lecanemab.  Here’s why: When my wife was diagnosed with early onset AD, we knew that most people, on average, progress through the stages of AD in about 8 years … some more quickly, some more slowly.  We thought that we could be reasonably confident of having at least 3 and maybe even 4 more really good years together before she would progress to moderate stages of AD.  And we did.  During those first few years after diagnosis, we traveled extensively both in this country and internationally.  We played our favorite word games like Scrabble and Boggle, continued to go bowling in our leagues, enjoyed going out by ourselves and with friends to see plays and movies, and enjoyed just sitting on a bench at the water’s edge on nice days. We had a very rewarding life together for those first three to four years after diagnosis.

Had a medication such as lecanemab or donanemab been available, would we have risked what turned out to be nearly four really good years together to take medication hoping my wife would be in the 35% of those who might gain an extra few good months, but all the while risking that she could be in the group of 24% who would suffer brain swelling or brain bleeds, stroke or death?  I think not. There is just too much downside risk, in my opinion … the high risk of negative side effects of this new medication simply outweigh any hope that there may be a slight reduction in the rate of decline for a few more months.  I await the published results and peer review of this new proposed medication later this summer or fall, but I am not very optimistic.

Personal Blog #30 … Medicare Quality Measures, Part II … 2/11/23

 

In my column posted on 11/4/22 … PB #29, “Medicare Quality Measures, Part l” … I wrote about a “quest” I was on to see if Medicare would consider making a doctor’s referral of an AD patient or caregiver to a support group qualify as a “quality measure.”  To briefly review, in response to my June article about support groups, a doctor had suggested that more doctors might refer AD patients and caregivers to support groups if referrals were considered Medicare “quality measures” … actions that would result in financial or other incentives for doctors to make such referrals.  I then described my unsuccessful efforts to reach someone at CMS … Centers for Medicare and Medicaid Services … who could give me information about this matter.  No email address was available for the head of CMS, Chiquita Brooks-LaSure, and no one contacted at CMS would give me her email address.

In late December, tired of waiting for a response from Medicare administrators I was able to email, I decided to try a hunch and sent an email to the head of CMS by using the same ID characteristics of email addresses for the lower level CMS administrators … first and last names or initials with periods and such, followed by the CMS email string of cms.hhs.gov.  Much to my surprise, within one day I received a detailed response from a high ranking CMS official who said my email to Brooks-LaSure was referred to him.  Aside from being very helpful, the official also provided me with websites to find additional information and wrote, in part:

“I directed your most recent email to our group of experts on quality measures, called the Quality Measurement and Value-Based Incentives Group (QMVIG) within the Center for Clinical Standards and Quality (CCSQ). You have definitely gotten to the right place to make sure your input is being submitted and that you’re getting the information from the best source.  I checked before I left for the holiday last week, and they were about to get back to you.  So you should hear from them soon.  I’ll follow up there again, and I’m sure they will respond back more fully with more robust information but … there are potentially payment incentives for our quality programs.”

I was very excited with this response and followed up by reading information on websites provided by the senior advisor.  However, a month went by with no response from QMVIG, so I wrote again to the CMS official in Ms. Brooks-LaSure’s office.  Within 48 hours I received a detailed response from an administrator of QMVIG.  Here are excerpts of that response to my email, specifically to three questions I raised:

“1. Would there be a specific billing or reimbursement advantage for doctors who would report using such a Medicare quality measure?  Potentially. Quality measures are commonly used in quality reporting programs or value based purchasing programs which seek to revise our payment systems by focusing on high value care (high quality/low cost). Depending upon the care setting, a program may apply penalties or bonuses based on provider performance on quality metrics. Some areas where Medicare does have payment is on caregiver health risk assessment through CPT code 96161. Additionally, through Medicare’s cognitive assessment and care plan services CPT code 99483, clinicians can refer people with suspected or diagnosed dementia to social services (such as support groups) and determine caregiver willingness to furnish care: https://www.cms.gov/files/document/cognitive-assessment-care-plan-services-cpt-code-99483.pdf

2. Would there be any other specific advantage to doctors who would report using such a Medicare quality measure? Other advantages include the ability to share performance information on measures with the public, which can be used as consumer tools when selecting a provider and leveraging results of quality measurement to identify areas where there is room for quality care improvement.

3. If the answer to questions 1 and/or 2 is yes, what would be my next step in trying to have Medicare consider AD support group referrals as "quality measures." It is a long process to have something be considered for a quality measure, and usually involves having a measure developer who has experience developing a measure – as quality measures used in federal programs require strict definitions, specifications, and testing for validity and reliability. However any measure by any developer may be submitted to CMS for consideration. Please see the Measure Blueprint for more information on this process (https://mmshub.cms.gov/blueprint-measure-lifecycle-overview). The measure would then be submitted to a consensus-based entity for endorsement, such as the National Quality Forum (https://www.qualityforum.org/what_we_do.aspx). The measure ultimately needs to be submitted to the Measures Under Consideration list. Information on the pre-rulemaking process can be found here https://mmshub.cms.gov/Pre-Rulemaking-Resources.”

My initial response to this administrator’s email, which also included a lot more relevant information, was that the CMS bureaucratic process for something to become a Medicare “quality measure” was a navigational process beyond my capabilities.  After checking out the websites and familiarizing myself more with the bureaucratic hoops I’d have to go through to make my quest successful, my initial response was confirmed.  I emailed the QMVIG administrator telling her that I now planned to contact an advocacy organization with the resources and expertise to deal with the CMS bureaucracy …perhaps AARP, The Alzheimer’s Association, or UsAgainstAlzheimer’s … since, as the administrator noted, “it is a long process to have something be considered for a quality measure, and usually involves having a measure developer who has experience developing a measure.”  My experience with educational and non-profit organizations is that they almost always hire or already have on staff one or more specialized individuals with the precise experience necessary in order to apply for state or federal grants in their field, and this quality measure quest seems to be much like a state or federal  grant application process.  I would expect a large AD advocacy organization to have people with such experience.

I plan to forward what I have learned to one or more AD advocacy organizations and hope one of them will pursue this quest to have CMS recognize doctor referrals to AD support groups as quality measures.  Then, perhaps, more people with AD and their caregivers will learn more about support groups and benefit from attending such groups.

Personal Blog #29 … Medicare Quality Measures, Part I … 11/4/22

 A doctor who read my June article, “Alzheimer’s Disease Support Groups,” suggested that if a support group referral could be declared a “quality measure” by Medicare, perhaps more doctors would discuss the importance of AD support groups and where their AD patients and caregivers could find them. 

I decided to follow up to learn more about Medicare “quality measures” and, specifically, to find out if more doctors might refer AD patients and caregivers to AD support groups if such referrals were considered “quality measures.”

My interaction with the Medicare bureaucracy began with a Google search.  I Googled the question, “Who is in charge of Medicare?” hoping to learn who I could email to find out more about quality measures.  The main Medicare website, cms.gov, states that “The Centers for Medicare & Medicaid Services (CMS) is the federal agency that runs the Medicare Program.  CMS is a branch of the Department of Health & Human Services (HHS).”  However, that site did not provide me with any email addresses.

I next Googled, “Who is the administrator in charge of Medicare?”  The first item that popped up was the name (and picture) of the person in charge and I read her biography on that site.  Chiquita Brooks-LaSure is the “Administrator for the Centers for Medicare and Medicaid Services (CMS).”  The site noted that LaSure has oversight responsibilities for many programs, including “Medicare, Medicaid, the Children's Health Insurance Program (CHIP), and the HealthCare.gov health insurance marketplace.”

Very helpful information, but I could not find an email address for LaSure at that or any other CMS site.  However, the cms.gov site, did provide brief biographies for the other three top Medicare administrators … the Principal Deputy Administrator & Chief Operating Officer, the Chief of Staff, and the Deputy Chief Operating Officer.  Only the Deputy Chief Operating Officer provided an email address, so I sent an email to Karen Jackson, Deputy Chief Operating Officer.  According to information on the cms.gov site, Jackson “provides executive leadership for CMS’s mission support functions …”

After a month passed and I still had received no response to my email, I searched to find another email address for someone who could answer my question, but found none.  Eventually, I ended up in an “online chat” with a helpful person, Brittany, at cms.gov.  Brittany placed me on hold several times to search for an email address, but she was unable to provide me with any email address for a top administrator other than for Jackson.  I told Brittany that surely there must be SOMEONE in the entire Medicare bureaucracy responsible for replying to emails from the public, but she was unable to find anyone else.

At that point, however, Brittany provided me with a helpful lead by referring me to another CMS agency, the “Quality Improvement Organization (QIO) Program.”  When I went to the QIO program page on the cms.gov site, I found this information: “The QIO Program, one of the largest federal programs dedicated to improving health quality for Medicare beneficiaries, is an integral part of the U.S. Department of Health and Human (HHS) Services' National Quality Strategy for providing better care and better health at lower cost. By law, the mission of the QIO Program is to improve the effectiveness, efficiency, economy, and quality of services delivered to Medicare beneficiaries.”

I sent off an email to that QIO email address that basically restated my email to Karen Jackson a month earlier:

-------------------------

I am hoping that you can help me. I am a former Alzheimer's disease (AD) spouse caregiver and I write frequently for publication about AD issues to help raise awareness and to help other caregivers. In one of my recent articles, I wrote about a problem that existed a dozen years ago and continues to exist today ... too many doctors do not alert AD patients and caregivers to the availability and helpfulness of local support groups.

A doctor who read my article said that if an AD support group referral were to be considered a Medicare "quality measure," perhaps more doctors would inform their patients and caregivers about how helpful support groups can be.  Based upon that doctor's comment, I have 2 questions:

 1. Is there a billing or reimbursement advantage for doctors who report using Medicare quality measures?

2. Is there any other advantage to doctors who use Medicare quality measures?  If a support group referral could become a "quality measure" that might lead to more AD patients and/or their caregivers seeking out such groups, what steps can I take to have Medicare consider such referrals as "quality measures."

 Thank you for your time and consideration.

---------------------------

Hopefully there will be a Part II to this blog with a response from someone at QIO about Medicare quality measures, and if AD support groups discussions/referrals could become quality measures.  It is truly a shame that so many people with AD and their caregivers are unaware of the existence of support groups and how helpful such groups can be on their AD journey.  Whereas there are many more support groups today than there were back in 2009 when I first sought such groups, doctors today are still not routinely referring their AD patients and caregivers to support groups.  Maybe, just maybe, that doctor who commented to me about my article was right … maybe, just maybe, more doctors would make their AD patients and caregivers aware of such groups if doing so were considered a quality measure by Medicare.  Stay tuned!