How groupthink governs medical research and commercial treatment protocols
(I write mostly at io-fund.com and commonstock.com, and you can check out the article here as well (with access to linked trades and my portfolio, and nicer formatting):
https://share.commonstock.com/xpDbSSY0yhb
We saw recently that the controversially FDA granted approval for Biogen’s new Alzheimer’s drug after spotty and possibly inconclusive trial results, and Biogen’s stock popped 40% on the news.
(3m stock chart of BIIB)
From Fierce Biotech, we see that all the drug companies want to join the party, and Acumen Pharma jumped 42% on its IPO yesterday ([link](https://www.fiercebiotech.com/biotech/acumen-surges-first-day-trading-following-aduhelm-approval-lilly-alzheimer-s-developments)).
- _Virginia-based Acumen finally reached the clinic this year with its antibody against amyloid-beta oligomers. It’s a long time coming for the Alzheimer’s candidate, ACU193, which emerged out of a collaboration with Merck that originally ran from 2003 to 2011._
- _The fresh proceeds will bankroll a phase 1 trial meant to produce data by the end of 2022. A phase 2 portion of a phase 2/3 clinical trial will then commence in 2023, Acumen has said._
- _Last week, Eli Lilly said it would file for accelerated approval of its Alzheimer’s therapy candidate, donanemab, later this year. Biogen and its Japanese partner Eisai won an FDA [breakthrough-therapy designation](https://investors.biogen.com/news-releases/news-release-details/eisai-and-biogen-inc-announce-us-fda-grants-breakthrough-therapy) for their anti-amyloid beta protofibril antibody. And, also last week, Bristol Myers Squibb put its foot in the door with a payment of $80 million to Prothena to [opt in on a license](https://ir.prothena.com/news-releases/news-release-details/prothena-announces-bristol-myers-squibb-opt-anti-tau-prx005) for anti-tau therapy PRX005._
- _Acumen’s IPO arrived the same day speculation emerged around Roche’s Alzheimer’s drug hopeful. The Swiss Big Pharma shot down rumors about an early approval filing that circulated from a Jefferies research note, saying it was focused on a phase 3 trial for gantenerumab._
- _Acumen’s potential FDA approval would likely be years behind Biogen’s and would fall behind Lilly’s, if donanemab gets the nod, which would put Acumen in the difficult position of needing to prove ACU193 different from those already on the market. Competing with a $56,000-a-year drug could be a hefty battle._
- _In its IPO filing, Acumen said ACU193 hardly binds with amyloid plaque and instead is meant to narrow in on amyloid-beta oligomers. This means the drug reaches the primary toxin behind the initiation and propagation of Alzheimer’s, the company claims, making it less likely to produce amyloid-related imaging abnormalities._
Alzheimer’s is a brutal disease and affects so many families, and it was this urgent demand for treatment that possibly caused the FDA to approve the Biogen drug in face of spotty data and many protests.
But, notice how everyone is targeting the same strategies — Amyloid and Tau. What if those indicators are not the cause of Alzheimer’s but rather a side effect or an interesting non-deterministic corrrelation?
Watch this 60 minutes’ episode on Alzheimers, and you’ll see the evidnece of people with amyloid not exhibiting any symptoms of Alzheimers and vice-versa.
https://www.cbsnews.com/news/long-life-study-60-minutes-2021-05-30/
How did we get here with everyone following the same approaches? Wouldn’t innovation suggest that people should try DIFFERENT approaches in order to let the evidence dictate which approach wins? Sadly, humans don’t operate that way — we are selfish and vindictive and tribal, or at least many people in the higher echelons of research who have the power to reward their friends and block their rivals.
Stat+ has the story: The maddening saga of how an Alzheimer’s ‘cabal’ thwarted progress toward a cure for decades ([link](https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/))
- _In more than two dozen interviews, scientists whose ideas fell outside the dogma recounted how, for decades, believers in the dominant hypothesis suppressed research on alternative ideas: They influenced what studies got published in top journals, which scientists got funded, who got tenure, and who got speaking slots at reputation-buffing scientific conferences._
- _This stifling of competing ideas, say a growing number of scholars, is a big reason why there is no treatment for Alzheimer’s. (The four approved drugs have no effect on the disease, providing only a temporary memory boost.)_
- _The scientists described the frustrating, even career-ending, obstacles that they confronted in pursuing their research. A top journal told one that it would not publish her paper because others hadn’t. Another got whispered advice to at least pretend that the research for which she was seeking funding was related to the leading idea — that a protein fragment called beta-amyloid accumulates in the brain, creating neuron-killing clumps that are both the cause of Alzheimer’s and the key to treating it. Others could not get speaking slots at important meetings, a key showcase for research results. Several who tried to start companies to develop Alzheimer’s cures were told again and again by venture capital firms and major biopharma companies that they would back only an amyloid approach._
- _“The amyloid hypothesis has been one of the most tragic stories [in] disease research,” said neurobiologist Rachael Neve of Massachusetts General Hospital._
- _Research focused on amyloid, and the development and testing of experimental drugs targeting it, have sucked up billions of dollars in government, foundation, and pharma funding with nothing to show for it. While targeting amyloid may or may not be necessary to treat Alzheimer’s, it is not sufficient, and the additional steps almost certainly include those that were ignored, even censored._
Jackson labs writes up their approach on moving beyond Amyloid in tryng to beat Alzheimer’s:
In Jackson’s blog — you’ll note that they call out CRISPR as a promising path to tackling Alzheimers:
- _At JAX, the research program is exploring multiple aspects of AD. The MODEL-AD Center, led at JAX by Greg Carter and Gareth Howell, is using patient population data to identify genetic variants associated with Alzheimer’s disease. Recent work revealed two distinct subtypes within the patient data, one associated with chronic inflammation, the other not. The inflammation signature is strong when looking at patient cohorts that haven’t been stratified, so characterizing and identifying the patients with the non-inflammatory disease subtype has important implications for both ongoing research and clinical care._
- _Another important current MODEL-AD effort is to improve mouse models of the disease to better reflect patient biology and disease pathology. The most promising genetic variants identified in patients are being engineered into the mice using CRISPR, the most advanced genetic engineering tool available. Furthermore, mice that exhibit AD-like traits can be imaged using new techniques to visualize disease progression. They are also analyzed at the molecular level to validate their relevance to human disease. Ongoing projects include seeing how multiple variants combine to affect disease onset and progression, as well as assessing the impact of diet and exercise._
Any doctors on this site available to comment on this research paper titled Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer’s Disease
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797629/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797629/)
Personally, I see a lot of risk in these treatment programs — and while the market may reward initial news on results — you can see how crowded the space is, how long the road is for many of these prospective trials, and the risks of efficacy loom large. Biogen is already selling off, and I suspect it will continue to give up gains.
I have no position in any of the companies listed above, and at present I continue to favor other areas of biotech including CRISPR companies.
