Criminal investigation if biotech company manipulated research for Alzheimer's drug

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TheresaB
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Criminal investigation if biotech company manipulated research for Alzheimer's drug

Post by TheresaB »

From this short article reported by Reuters: Exclusive: Cassava Sciences faces U.S. criminal probe tied to Alzheimer's drug, sources say
The U.S. Justice Department has opened a criminal investigation into Cassava Sciences Inc (SAVA.O) involving whether the biotech company manipulated research results for its experimental Alzheimer's drug, two people familiar with the inquiry said.
From Cassava Sciences website https://www.cassavasciences.com/simufilam:
Simufilam (formerly known as PTI-125) is an investigational drug that represents an entirely new approach to treat Alzheimer’s disease.

Importantly, we do not seek to clear amyloid out of the brain. Our science is based on stabilizing a critical protein in the brain.

Simufilam is a proprietary, small molecule (oral) drug that restores the normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain.

The underlying science for simufilam is published in peer-reviewed journals, including Journal of Neuroscience, Neurobiology of Aging, Journal of Biological Chemistry, Neuroimmunology and Neuroinflammation and Journal of Prevention of Alzheimer’s Disease.

We are now in clinical studies to test a new and promising scientific approach for the treatment and diagnosis of Alzheimer's disease. If you are interested in being notified about clinical trials, click here.

Simufilam was developed in-house. Over the years, simufilam has been substantially funded by peer-review research grant awards from the National Institutes of Health (NIH).
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Re: Criminal investigation if biotech company manipulated research for Alzheimer's drug

Post by Greyhound »

Well that is some story. Apparently they redid their second phase trial and it was disclosed in their filings. The government requested additional information and no charges were filed against the company. Now the company is claiming they are having some success in the 3rd phase of the trial! There might not be enough evidence or it could be too difficult to find where the fraud if it was done to charge the company so their development is continuing. This is really a difficult case to understand from the legal point of view.
I read through the comments on the site below and I am still shaking my head in disbelief. Will this stalemate ever be resolved? Reform is needed in the drug approval process as too many failed drugs make it through the process like viox which killed over 100,000 before it was stopped. I believe I was injured by a failed drug that is approved and still in use but no doctor will ever admit to its faults as they all still use it. If 10% have a benefit they will not even tell you that 90% will get injured. It is even in specialist guidelines but patients believe their doctor and do not read guidelines!

https://seekingalpha.com/news/3861598-s ... uct-claims
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Re: Criminal investigation if biotech company manipulated research for Alzheimer's drug

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TheresaB wrote: Thu Jul 28, 2022 4:04 pm From this short article reported by Reuters: Exclusive: Cassava Sciences faces U.S. criminal probe tied to Alzheimer's drug, sources say
The U.S. Justice Department has opened a criminal investigation into Cassava Sciences Inc (SAVA.O) involving whether the biotech company manipulated research results for its experimental Alzheimer's drug, two people familiar with the inquiry said.
Call me a "glass-half-full" person, but I see this as news that the system works and the bad actors are in a world of trouble in a remarkably short amount of time. Although the FDA has not yet issued a hold, I would expect that before pumpkin spice latte returns to Starbucks this fall!

Here's a timeline of events just in the past 12 months:, including two other drugs suspended from AD trials following safety and/ore efficacy (not criminal actions) https://www.alzforum.org/therapeutics/simufilam
August 2021:
  • an anonymous citizen petition was filed with the FDA, requesting the agency halt ongoing simufilam trials. The complaint alleged instances of research misconduct involving the clinical trial biomarker data and previous, foundational research on the drug
  • The FDA posted a statement of concern on its website.
  • Soon after, several independent scientists reported instances of apparent data manipulation in several published studies (see PubPeer and Retraction Watch) and in the blood biomarker data on the 2021 AAIC poster (Science Integrity Digest blog).
January 2022
  • FDA issued a full clinical hold on Cortexyme's IND for atuzaginstat, which it is evaluating for the treatment of Alzheimer's and other neurodegenerative diseases.
  • [The FDA]sent a formal clinical hold letter to... Denali Therapeutics [for] the investigational drug DNL919, for...information relating to preclinical toxicology assessments. The FDA also suggested that changes be implemented on its informed consent form, investigator brochure and trial protocol.
February 2022 From BioSpace.comCassava 10K Filing Warns of Anticipated Hold, Paints Dire Picture of Alzheimer's SpaceFebruary 2022:
  • In its 10-K annual report filing dated February 28, the biotechnology firm warned investors that its operations and business could suffer down the line if it is unsuccessful in lifting the anticipated FDA hold ... The regulator has not yet issued any such letter to Cassava, but the company expects that its time is coming after rivals Denali Therapeutics and Cortexyme received theirs.
March 2022t
  • The journal PlosOne retracted five papers by Cassava academic collaborator Hoau-Yan Wang at CUNY; two had been co-authored with a Cassava employee
July 29, 2022:
  • Cassava Sciences stock is down 83% from one year ago, including a 21% drop after the DOJ news.
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Re: Criminal investigation if biotech company manipulated research for Alzheimer's drug

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Here is the results. NONE or if you think it is over. What about the other investigation? I have not seen any results yet and we may never hear the results as that is a possibility..
This is from the SEC the security exchange commission which investigates securities fraud.

The SEC Recommends Closing Cassava Sciences Investigation

Cassava Sciences is working on an Alzheimer's Disease (AD) small molecule drug called Simufilam, currently in phase 3 trials. Over 99% of AD therapies attempted have failed, which is why the company has chosen to take a novel approach.
...
Simufilam is a pill with no known safety issues after over a quarter of a million doses. Many other AD therapies are full of safety issues, such as Aduhelm from Biogen (BIIB), a good face of the amyloid theory drugs, that had a major problem with brain swelling and bleeds. Further, Simufilam is a pill compared to competitors who have chosen to pursue an IV injection method, such as Aduhelm. A pill is cheaper, safer, and more manageable. If Simufilam and an IV method are approved with the same benefit, the pill would far outperform the IV in sales.

While this drug and theory on AD is new to many investors and is still unknown by many scientists, it has actually been in development for over 15 years. Below is the company's slide on the development history.

Simufilam developmental history

Corporate Presentation

Method of Action

Simufilam had a dual method of action from binding to a single target. The result of this is the reduction of neurodegeneration and neuroinflammation. The traditional approach for years has been around the Amyloid theory, which:

"suggests that the deposition of Amyloid β (Aβ) in the brain triggers a chain of events, involving the deposition of phosphorylated Tau and other misfolded proteins, leading to neurodegeneration via neuroinflammation, oxidative stress, and neurovascular factors."

Cassava Sciences' theory is around Altered Filamin A (FLNA). What differentiates Cassava Sciences is that it is an entirely new theory on what causes AD. Below is the company's corporate slide on the method of action.

Method of Action Simufilam

Corporate Presentation

Clinical Data

AD is a disease of continual decline. A successful drug would noticeably slow the decline. An incredible drug could stop the decline. A Nobel prize-winning drug could reverse cognitive decline. Dr. Robert Howard, a professor of old age psychiatry and an expert in clinical trial design at University College London, said, "Generally, in this area, we would regard slowing or stopping of cognitive decline as a win."

Simufilam has reversed cognitive decline in 100 patients in an open-label trial at 12 months. Previously, the longest cognitive decline that has been reversed was six months. Below is the highlight of that trial.

12 month

Corporate Presentation

To show how drastic Cassava Sciences results are compared to other AD drugs, I have a graphic comparing them. In the chart are the clinical results of Biogen's Aduhelm, which received accelerated approval, Eisai's Lecanemab, which received breakthrough drug designation, Eli Lilly's (LLY) Donanemab, which received breakthrough drug designation, placebo averaged from multiple drug trials, and Roche's (OTCQX:RHHBY) Gantenerumab, which received breakthrough drug designation. Check out the graphic below.

comparison

Created

SEC Clearance

As seen below, the SEC has officially closed its case. The below document was obtained through a FOIA request. I have highlighted crucial wording.

SEC Cassava Sciences

SEC

EDIT 9/23/2022 by Jacob Braun

The company has since stated that they have never received a "termination letter," so early clearance reporting was false. However, the above document still appears valid. Changes to the headline have been made to reflect that the SEC has recommended a case closing instead of a clearance.
discl

Cassava Sciences

1. Cassava Sciences has stated that it intends to release 12-month data for 200 patients (100 patients have already been released) from its open-label extension trial.

2. In addition to 200 patient data, the company plans to release the biomarker data for 25 patients in that trial.

3. Recently, the company stated that results from its blood-based diagnostic test SavaDX should be released sometime between now and the first half of 2023. SavaDX could be worth over a billion dollars, but the company has put it on the back burner as it focuses on the real prize in Simufilam.

4. In mid-2023, the company will release data from its cognitive maintenance study. In this study, patients who have been on the drug open-label for 12 months will be randomly split into placebo and drug group trial arms for six months. This trial will give out placebo-controlled, drug withdrawal, and 18-month open-label data. All three of these pieces of data will give a much better picture to investors and could potentially propel the company to some elevated regulatory status considering that the company only added the CMS trial after meeting with the FDA in 2021.

cms

Corporate Presentation

5. Finally, we can expect phase 3 trial results in mid-2024 from both of the company's phase 3 trials. This is the data that will get the drug approved or denied and is the most critical event for the company.

phase three

Corporate Presentation

source
https://seekingalpha.com/article/454233 ... estigation
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Re: Criminal investigation if biotech company manipulated research for Alzheimer's drug

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The latest on the Alzheimer's drug simufilam and its developer Cassava, published by Science on October 12, 2023
A much-anticipated investigation by the City University of New York has accused neuroscientist Hoau-Yan Wang, a CUNY faculty member and longtime Cassava collaborator, of scientific misconduct involving 20 research papers. Many provided key support for simufilam’s jump from the lab into clinical studies and, given the CUNY report, some scientists are now calling for the two ongoing trials to be suspended.
The investigative committee found numerous signs that images were improperly manipulated, for example in a 2012 paper in The Journal of Neuroscience that suggested simufilam can blunt the pathological effects of beta amyloid, a protein widely thought to drive Alzheimer’s disease. It also concluded that Lindsay Burns, Cassava’s senior vice president for neuroscience and a co-author on several of the papers, bears primary or partial responsibility for some of the possible misconduct or scientific errors.
The entire article is here: Co-developer of Cassava’s potential Alzheimer’s drug cited for ‘egregious misconduct
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Re: Criminal investigation if biotech company manipulated research for Alzheimer's drug

Post by QueenJane »

So, where are we at? Can someone break this down for me? Is simufilam dead in the water? Another lie from the greedy and power-hungry at the expense of those in need?
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Re: Criminal investigation if biotech company manipulated research for Alzheimer's drug

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QueenJane wrote: Tue Oct 17, 2023 10:51 am So, where are we at? Can someone break this down for me? Is simufilam dead in the water? Another lie from the greedy and power-hungry at the expense of those in need?
Simufilam is not dead in the water yet, but the pressure is mounting:

As cited in the Science article quote from the post above, "some scientists are now calling for the two ongoing trials to be suspended."

From STAT news, It’s time for the FDA to halt Cassava Sciences’ Alzheimer’s clinical trials
The Food and Drug Administration should halt Cassava Sciences’ ongoing clinical trials in Alzheimer’s disease. That, and other thoughts on the fallout from the City University of New York investigation that raised serious doubts about the science underpinning the company’s experimental drug simufilam.

Patient safety is paramount to the FDA, so stopping Cassava’s two Phase 3 studies is the ethically correct thing to do. The FDA has the power to place clinical holds on experimental drugs when there’s evidence of an unacceptable safety risk to study participants. Simufilam doesn’t appear to be toxic. It’s not causing dangerous side effects. But study participants can also be harmed when they volunteer for a clinical trial based on false or misleading information about a drug’s potential efficacy.
The New York Times, Scientists Investigating Alzheimer’s Drug Faulted in Leaked Report

The Daily Mail in the UK $500m Alzheimer's drug scandal: NY scientist behind NIH-funded therapy busted for allegedly manipulating data in 20 research papers - now there are calls for trials to be cut off.

The Business Journals Austin's Cassava Sciences again under scrutiny for Alzheimer’s drug simufilam

If anyone happens upon any future updates hopefully it will be added to this thread. I will if I happen upon any.
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Re: Criminal investigation if biotech company manipulated research for Alzheimer's drug

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From StatNews, Cassava pulled back the curtain on its Alzheimer’s study — and revealed insurmountable problems. From the paywall protected article, "The conclusion, of course, is obvious: Simufilam is inactive. It’s an inert compound no more effective than a placebo." per author Adam Feuerstein, "When you account for the mismatched randomization at month 12, the placebo arm performs better than simuflam." Sad.
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