Aducanumab

[Anastasis 23475]

Here we go again.  This time for the bargain rate of $26,000.  I haven't looked at their data at all, so no opinion yet on whether it is as much of a fucking clown show approval as the last one, but looks like the approval once again hinges on a surrogate endpoint and not demonstrated clinical benefit. 

 

  

 

 

[Anastasis 23475]

And a write-up from Derek Lowe:

https://www.science.org/content/blog-post/lecanemab-s-rough-progress

Lecanemab's Rough Progress

The lecanemab story is not getting any less tangled. It's gradually come out that three patients in the trial of the anti-amyloid antibody died while on some sort of anticoagulant therapy - these were uncovered one by one in stories at Stat and here at Science. If I weren't such a sunny optimist I'd say "three patients so far". Eisai (the drug's developer) has sort of been pulled along on this story, because to the best of my knowledge they have not mentioned any of these cases until they were reported. And they have continued to state their opinion that lecanemab played no role in any of these deaths.

But this latest report makes that less clear as well. It turns out that the company revised the clinical consent form given to patients during the trial to include language about increased risk of death with the combination of lecanemab and anticoagulants: "While the overall risk of a major brain bleed is low with [lecanemab] treatment, the risk is higher in people who are also taking blood clot prevention medications. This risk is estimated to be more than 1 in 100 people, but less than 5 in 100 people. . .Bleeding in the brain, especially when you are taking medications that prevent blood clots, can be serious and can even lead to death. It is important to consider the risk of bleeding in your brain with the investigator before deciding whether or not to continue your participation in this study"

That's not so easy to square with earlier public statements like this one: ". . .all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause. . ." The latest story notes that the language in Eisai's consent form was strengthened over time, but it's not clear how quickly or when these versions propagaged out to the trial centers or to the patients. The deaths have occurred in the open-label extension phase of the clinical trial, from what I can see.

So this raises some tough questions about the FDA review of the antibody and what its labeling might be. And this just highlights what a mess the agency's earlier approval of Aduhelm has created. Not only do you have that precedent to deal with - if Sulla got his antibody approved, why not mine? - but that very approval is still being questioned. See this report from the House of Representatives, which states that the relationship between Biogen and the FDA was out of the ordinary during the approval process, that they "inappropriately collaborated" on the text of briefing documents, and that the FDA did not follow its own rules on documenting the meetings between the parties. This was not a confidence-building exercise. And it's not going to make the eventual deliberations over lecanemab any easier. But hey, accelerated approval is expected to be granted this week, so it looks like we'll sort all that out while the drug is being sold to patients.

You'll note that the parts of this post that talk about lecanemab reference Eisai, while the parts that reference Aduhelm reference Biogen. In reality, though, both these antibodies are part of a collaborative effort between the two companies. Biogen seems to have taken the regulatory lead on Aduhelm, with the results just mentioned, and it looks like Eisai decided that surely they could do a better job of it for lecanemab. Reports of tension between the two companies on this issue don't seem to be going away.

[MoJames 8244]

On 1/6/2023 at 12:50 PM, Anastasis said:

Here we go again.  This time for the bargain rate of $26,000.  I haven't looked at their data at all, so no opinion yet on whether it is as much of a fucking clown show approval as the last one, but looks like the approval once again hinges on a surrogate endpoint and not demonstrated clinical benefit. 

 

Same shit different company. This one wasn't fast tracked so they will be able to advertise it. It's about to go batshit.

Edited June 15, 2023 by MoJames

[Anastasis 23475]

https://www.statnews.com/2024/02/06/biogen-adulhelm-fda-eisai-lecanemab-lilly-donanemab-alzheimers-drugs/
 

Aduhelm was a mess — and it could happen again

[texasdago 7575]

Genesis' Aducanumababacab is so underrated

 

[Bevo 13579]

Hasn't it already been found that amyloid plaques are not the cause of Alzheimers but rather a finding among Alzheimers patients?

[South Austin 52519]

17 hours ago, texasdago said:

Genesis' Aducanumababacab is so underrated.

I've been a big Genesis fan ever since the release of their 1980 album, Duke. Before that, I really didn't understand any of their work. Too artsy, too intellectual. It was on Duke where Phil Collins' presence became more apparent. I think Invisible Touch was the group's undisputed masterpiece. It's an epic meditation on intangibility. At the same time, it deepens and enriches the meaning of the preceding three albums. Christy, take off your robe. Listen to the brilliant ensemble playing of Banks, Collins and Rutherford. You can practically hear every nuance of every instrument. Sabrina, remove your dress. In terms of lyrical craftsmanship, the sheer songwriting, this album hits a new peak of professionalism. Sabrina, why don't you, uh, dance a little. Take the lyrics to Land of Confusion. In this song, Phil Collins addresses the problems of abusive political authority. In Too Deep is the most moving pop song of the 1980s, about monogamy and commitment. The song is extremely uplifting. Their lyrics are as positive and affirmative as anything I've heard in rock. Christy, get down on your knees so Sabrina can see your asshole. Phil Collins' solo career seems to be more commercial and therefore more satisfying, in a narrower way. Especially songs like In the Air Tonight and Against All Odds. Sabrina, don't just stare at it, eat it. But I also think Phil Collins works best within the confines of the group, than as a solo artist, and I stress the word artist. 

[smokebomb 357]

Some researchers are thinking Alzheimer’s may actually be an autoimmune disease:

https://www.sciencealert.com/alzheimers-might-not-actually-be-a-brain-disease-expert-reveals
 

Quote

Alzheimer's Might Not Actually Be a Brain Disease, Expert Reveals

The Conversation

The pursuit of a cure for Alzheimer's disease is becoming an increasingly competitive and contentious quest with recent years witnessing several important controversies.

In July 2022, Science magazine reported that a key 2006 research paper, published in the prestigious journal Nature, which identified a subtype of brain protein called beta-amyloid as the cause of Alzheimer's, may have been based on fabricated data.

One year earlier, in June 2021, the US Food and Drug Administration had approved aducanumab, an antibody-targeting beta-amyloid, as a treatment for Alzheimer's, even though the data supporting its use were incomplete and contradictory.

Some physicians believe aducanumab never should have been approved, while others maintain it should be given a chance.

With millions of people needing an effective treatment, why are researchers still fumbling in this quest for a cure for what is arguably one of the most important diseases confronting humankind?

Escaping the beta-amyloid rut

For years, scientists have been focused on trying to come up with new treatments for Alzheimer's by preventing the formation of brain-damaging clumps of this mysterious protein called beta-amyloid.

In fact, we scientists have arguably got ourselves into a bit of an intellectual rut concentrating almost exclusively on this approach, often neglecting or even ignoring other possible explanations.

Regrettably, this dedication to studying the abnormal protein clumps has not translated into a useful drug or therapy. The need for a new "out-of-the-clump" way of thinking about Alzheimer's is emerging as a top priority in brain science.

My laboratory at the Krembil Brain Institute, part of the University Health Network in Toronto, is devising a new theory of Alzheimer's disease.

Based on our past 30 years of research, we no longer think of Alzheimer's as primarily a disease of the brain. Rather, we believe that Alzheimer's is principally a disorder of the immune system within the brain.

The immune system, found in every organ in the body, is a collection of cells and molecules that work in harmony to help repair injuries and protect from foreign invaders.

When a person trips and falls, the immune system helps to mend the damaged tissues. When someone experiences a viral or bacterial infection, the immune system helps in the fight against these microbial invaders.

The exact same processes are present in the brain. When there is head trauma, the brain's immune system kicks into gear to help repair. When bacteria are present in the brain, the immune system is there to fight back.

Alzheimer's as autoimmune disease

We believe that beta-amyloid is not an abnormally produced protein, but rather is a normally occurring molecule that is part of the brain's immune system. It is supposed to be there.

When brain trauma occurs or when bacteria are present in the brain, beta-amyloid is a key contributor to the brain's comprehensive immune response. And this is where the problem begins.

Because of striking similarities between the fat molecules that make up both the membranes of bacteria and the membranes of brain cells, beta-amyloid cannot tell the difference between invading bacteria and host brain cells, and mistakenly attacks the very brain cells it is supposed to be protecting.

This leads to a chronic, progressive loss of brain cell function, which ultimately culminates in dementia – all because our body's immune system cannot differentiate between bacteria and brain cells.

When regarded as a misdirected attack by the brain's immune system on the very organ it is supposed to be defending, Alzheimer's disease emerges as an autoimmune disease.

There are many types of autoimmune diseases, such as rheumatoid arthritis, in which autoantibodies play a crucial role in the development of the disease, and for which steroid-based therapies can be effective. But these therapies will not work against Alzheimer's disease.

The brain is a very special and distinctive organ, recognized as the most complex structure in the Universe. In our model of Alzheimer's, beta-amyloid helps to protect and bolster our immune system, but unfortunately, it also plays a central role in the autoimmune process that, we believe, may lead to the development of Alzheimer's.

Though drugs conventionally used in the treatment of autoimmune diseases may not work against Alzheimer's, we strongly believe that targeting other immune-regulating pathways in the brain will lead us to new and effective treatment approaches for the disease.

Other theories of the disease

In addition to this autoimmune theory of Alzheimer's, many other new and varied theories are beginning to appear. For example, some scientists believe that Alzheimer's is a disease of tiny cellular structures called mitochondria – the energy factories in every brain cell.

Mitochondria convert oxygen from the air we breathe and glucose from the food we eat into the energy required for remembering and thinking.

Some maintain that it is the end-result of a particular brain infection, with bacteria from the mouth often being suggested as the culprit. Still others suggest that the disease may arise from an abnormal handling of metals within the brain, possibly zinc, copper, or iron.

It is gratifying to see new thinking about this age-old disease. Dementia currently affects more than 50 million people worldwide, with a new diagnosis being made every three seconds. Often, people living with Alzheimer's disease are unable to recognize their own children or even their spouse of more than 50 years.

Alzheimer's is a public health crisis in need of innovative ideas and fresh directions.

For the well-being of the people and families living with dementia, and for the socioeconomic impact on our already stressed health-care system coping with the ever-escalating costs and demands of dementia, we need a better understanding of Alzheimer's, its causes, and what we can do to treat it and to help the people and families who are living with it.