- BRAIN GAMES? Whistleblowers and former lab members suggest star neuroscientist Berislav Zlokovic may have manipulated data that support a major stroke trial and important Alzheimer’s research"Because of its potential to address an unmet medical need, the U.S. Food and Drug Administration (FDA) gave the compound “fast track” status, with the prospect of “accelerated approval and priority review.” ZZ Biotech says the new trial should start within a few months.
But a 113-page dossier obtained by Science from a small group of whistleblowers paints a less encouraging picture. The dossier, which they submitted to NIH, highlights evidence from the phase 2 trial that the experimental remedy might have actually increased deaths in the first week after treatment: Six of the 66 stroke patients who received 3K3A-APC died within this period, compared with one among 44 in the placebo group, although the death rate evened out after a month. Patients who received the drug also trended toward greater disability and dependency at the end of the trial, 90 days after treatment.
Deepening the concern, the dossier also highlights evidence that dozens of papers from Zlokovic’s lab—including many supporting the idea that the compound was ready for human testing—contain seemingly doctored data that suggest scientific misconduct." -- Science.org, by Charles Piller, 11/13/2023 - NIH puts hold on $30 million trial of potential stroke drugScience.org, Charles Piller, 12/1/2023
- USC neuroscientist faces scrutiny following allegations of data manipulationLos Angeles Times, Corinne Purtill, Melody Petersen, 11/24/2023
Biogen re-evaluated the data a number of times and eventually suggested there was an improvement in mental capacity among dementia sufferers – of less than one per cent....Worryingly, safety data published in November showed that 41 per cent of patients who took the drug suffered major side effects. The most serious of these include a type of swelling and bleeding in the brain known as ARIA-E. An FDA Adverse Event Reporting System case report shows that at least one woman died from this complication." -- Daily Mail
- ICER Publishes Final Evidence Report and Policy Recommendations on Aducanumab for Alzheimer’s Disease
"Independent appraisal committee unanimously determined the evidence is not adequate to demonstrate that aducanumab provides a net health benefit"-- ICER (Institute for Clinical and Economic Review) - AducanumabUniversity of California San Francisco, Weill Institute for Neuro sciences Memory and Aging Center. (2021). Aducanumab. Memory and Aging Center. https://memory.ucsf.edu/aducanumab.
- Aducanumab (marketed as Aduhelm) InformationU.S. Food & Drug Administration (FDA)
- Aducanumab for the Treatment of Alzheimer’s Disease: Clinical Overview of EfficacyFDA, Kevin M. Krudys, PhD, Clinical Efficacy Reviewer, Division of Neurology 1, Office of Neuroscience, Center for Drug Evaluation and Research
- Aduhelm is FDA Approved for Alzheimer's, But Does it Work?
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Healthcare Triage, YouTube video, 7/29/2021 - Aduhelm Official Patient SiteBiogen Support Services
- Aduhelm price drop prompts Becerra to rethink hike to Part B 2022 premiumsFierce Healthcare, by Robert King, 1/10/2022
- The Alzheimer’s Treatment Controversy: Implications of Accelerated Drug Approvals
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Harvard T.H. Chan School of Public Health, YouTube video, livestreamed on 7/20/2021 - Approval of Aducanumab for Alzheimer Disease—the FDA’s PerspectiveDunn B, Stein P, Cavazzoni P. Approval of Aducanumab for Alzheimer Disease—the FDA’s Perspective. JAMA Intern Med. Published online July 13, 2021. doi:10.1001/jamainternmed.2021.4607
- Biogen's Aduhelm faces a key coverage decision next week. Which way will Medicare rule, and how much does it matter?Fierce Pharma, by Angus Liu, 1/6/2022
- Biogen pulled Aduhelm paper after JAMA demanded editsHerman, B. (2021, July 27). Biogen pulled aduhelm paper After JAMA demanded edits. Axios. https://www.axios.com/biogen-jama-aduhelm-clinical-trial-results-publish-fc7c2876-a684-4bfc-8462-4165f57d735a.html.
- Biogen’s reckoning: How the Aduhelm debacle pushed a troubled company and its fractured leadership to the brinkSTAT, By Adam Feuerstein and Damian Garde, 12/8/2021
- Concerns Grow Over Safety of Aduhelm After Death of Patient Who Got the Drug"Last week, Brian Abrahams, a biotech analyst with RBC Capital Markets who has a medical degree, wrote to clients that he had obtained the woman’s case report through a public records request and had concluded that the brain swelling probably caused the woman’s death and “that this is likely to have been caused by aducanumab.” -- NewYorkTimes.com, by Pam Belluck, 11/22/2021
- Congress Asks FDA for More Information on Aduhelm ApprovalAlzheimer's News Today, by Marisa Wexler MS, 9/9/2021
- Controversial Alzheimer’s drug approval could affect other diseasesMullard, A. (2021). Controversial Alzheimer’s drug approval could affect other diseases. Nature, 595(7866), 162–163. https://doi.org/10.1038/d41586-021-01763-9
- Critical elements of leading Alzheimer’s study possibly fraudulentTheguardian.com, Jessica Glenza, 7/23/2022
- Dr. Gautam Desai discusses new FDA-approved Alzheimer’s drug Aduhelm
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Fox 4 News, YouTube video, 6/23/2021 Dr. Gautam Desai, KCU-Kansas discusses the drug Aduhelm. - FDA Commissioner Calls For Inspector General Probe Into Biogen Alzheimer’s Drug ApprovalRosenbaum, L. (2021, July 9). FDA Commissioner calls FOR Inspector GENERAL probe into Biogen Alzheimer's drug approval. Forbes. https://www.forbes.com/sites/leahrosenbaum/2021/07/09/fda-commissioner-calls-for-inspector-general-probe-into-biogen-alzheimers-drug-approval/?sh=7acbcdbd3d47.
- FDA faces critical test with Alzheimer's drug decisionHerman, B. (2021, June 4). Alzheimer's drug decision to TEST FDA's rigor. Axios. https://www.axios.com/fda-aducanumab-biogen-alzheimers-drug-approval-3b148700-97fc-417c-9b75-42ea8e368728.html.
- FDA releases fresh details on internal debate over controversial Alzheimer’s drugMcGinley, L. (2021, June 22). FDA releases fresh details on internal debate over controversial Alzheimer’s drug. Washington Post. https://www.washingtonpost.com/health/2021/06/22/aducanumab-aduhelm-alzheimers-drug-controversy-/.
- FDA seeks probe into its talks with Biogen before Alzheimer's drug approvalReuters.com, by Manas Mishra, 7/9/2021 "Aduhelm was approved despite one of its two large-scale clinical trials failing to show a benefit to patients." -- Reuters
- The FDA’s Approval Of Aduhelm: Potential Implications Across A Wide Range Of Health Policy Issues And StakeholdersSachs, R. (2021, June 6). The FDA’s Approval Of Aduhelm: Potential Implications Across A Wide Range Of Health Policy Issues And Stakeholders [web log]. Retrieved September 9, 2021, from https://www.healthaffairs.org/do/10.1377/hblog20210609.921363/full/.
- FDA’s Decision to Approve New Treatment for Alzheimer’s DiseaseU.S. Food & Drug Administration (FDA)
- Group Wants FDA Leaders Ousted Over Alzheimer's Drug ApprovalWebMD, by Alica Ault, 6/17/2021
- Huge Part Of Potential Patient Pool Excluded In Aduhelm Clinical TrialsKaiser Family Foundation, 9/13/2021 updated 9:17 am
- Inside ‘Project Onyx’: How Biogen used an FDA back channel to win approval of its polarizing Alzheimer’s drug"The decision has shifted the landscape for Alzheimer’s drugs, clearing the way for Eli Lilly to apply for approval of a similar medicine. But it has also spurred disbelief among some pharmaceutical executives. “This is a disaster on so many levels,” said one, asking for anonymity to speak candidly about another drug maker. “I frankly cannot fathom how the FDA decided to approve a drug that seems to have more evidence that it causes harm than good.” -- MSN.com, Boston Globe by Adam Feuerstein, Matthew Herper, and Damian Garde, 6/29//2021
- Many red flags raised by the FDA approval of aducanumabYahoo.com, CNW Telbec, 8/12/2021
- A new Alzheimer’s drug has been approved. But should you take it?"Concerns over the FDA approval of Aduhelm have led to further investigation into its safety, effectiveness, and cost. Some insurers are declining to cover it and some medical centers have decided not to prescribe it ...To take the drug, you need an intravenous infusion every four weeks — forever. Thirty percent of those who took the drug had a reversible swelling of the brain, and more than 10% had tiny brain bleeds." -- Harvard Health Publishing, by Andrew E. Budson, MD 7/15/2021
"...[B]ombshell allegations that a pivotal study on the cause of Alzheimer’s disease contained manipulated results, potentially leading other scientists down a blind alley, hindering the development of effective treatments and giving false hope to patients and their families." -- Daily Mail
"Pharmaceutical companies over more than a decade have spent billions of dollars on research to find a treatment for Alzheimer's. Research has largely focused on the beta amyloid protein, which accumulates in the brains of patients with Alzheimer's years before they experience memory loss. Researchers have hypothesized that the buildup in the brain from the beta-amyloid was responsible for the cognitive decline seen in Alzheimer's patients. However, an estimated 150 to 300 experimental Alzheimer's treatments have failed to show clinical benefits—and many of those treatments targeted the beta amyloid protein." -- Advisory.com
"But the Science investigation, following so many failed amyloid beta drug trials, suggests a colossal scientific failure that may have led to needless suffering by those living with Alzheimer’s Disease and their family members." -- Forbes.com
- Allegations of fabricated research undermine key Alzheimer’s theoryNBCnews.com, by Aria Bendix and Denise Chow, 7/26/2022
- Alzheimer’s: Alleged image manipulation in seminal paper casts doubt on leading hypothesis of diseaseBMJ 2022;378:o2041
http://dx.doi.org/10.1136/bmj.o2041
Published: 17 August 2022 - Alzheimer’s Research in Turmoil as Sleuths Cast Doubt on Field-Defining PaperScience the Wire, Amrit B.L.S., 7/22/2022
- BLOTS ON A FIELD? A neuroscience image sleuth finds signs of fabrication in scores of Alzheimer’s articles, threatening a reigning theory of the diseaseScience.org, by Charles Piller, 7/21/2022
- Company’s Alzheimer’s treatment study earns a flagRetraction Watch, Adam Marcus, 8/8/2022
- Internal review found ‘falsified data’ in Stanford President’s Alzheimer’s research, colleagues allegeThe Stanford Daily, by Theo Baker, 2/17/2023
- Investigation into pivotal Alzheimer's study raises questions on suspected disease culpritUSAToday.com, Ken Alltucker and Karen Weintraub, 7/29/2022
- A specific amyloid-β protein assembly in the brain impairs memoryArticle metrics for a a now controversial article published in Nature in 2006: A specific amyloid-β protein assembly in the brain impairs memory
- Stanford president criticizes Daily report on alleged research falsification as ‘replete with falsehoods’The Stanford Daily, by Kate Selig, 2/17/2023
- ‘Manipulated’ Alzheimer’s data may have misled research for 16 yearsThe Telegraph, Sara Knapton, 7/21/2022
- ‘MTL knew’: Misconduct allegations independently corroborated in private correspondence to special committeeThe Stanford Daily, by Theo Baker, 3/6/2023
The company is now facing an investigation from the Securities and Exchange Commission (SEC), and has had some of its trial data either rescinded or marked by journals as potentially manipulated." -- Daily Mail
Cassava Sciences faces U.S. criminal probe tied to Alzheimer's drug "Cassava has received more than $20 million from the U.S. National Institutes of Health to support developing simufilam...Research misconduct may distort NIH funding decisions, the overall integrity of the research we support and the public's trust in science and resulting outcomes." -- www.reuters.com
- ‘Damning’ FDA inspection report undermines positive trial results of possible Alzheimer’s drugScience.org article by Charles Piller, 3/11/2024. From the website: "A version of this story appeared in Science, Vol 383, Issue 6688."
- Co-developer of Cassava’s potential Alzheimer’s drug cited for ‘egregious misconduct’Science.org, by Charles Piller, 10/12.2023
- Cassava implies 'short-sellers' to blame for leaking CUNY report alleging scientific misconductFierceBiotech.com, by Max Bayer, 10/13/2023
- Alzheimer's drug developed by Wall Street darling Cassava Sciences is under fire as scientists accuse it of manipulating trial data: Company faces SEC investigationDailymail.co.uk, by Mansur Shaheen, 4/19/2022
- Biotech’s data supporting Alzheimer’s trials under scrutinyRetraction Watch, Adam Marcus, 8/26/2021
- Facing backlash from scientific community, Cassava drops interim Alzheimer's data with plenty of caveatsFierce Biotech, Biotech, Annalee Armstrong, 9/22/2021
- Five studies linked to Cassava Sciences retracted"A researcher at the center of questions about a biotech’s controversial experimental treatment for Alzheimer’s disease has lost five papers in PLOS One." -- Retraction Watch, Adam Marcus, 3/30/2022
- Memory Games, Part I: "The Data Is Available Upon Request" An Introduction to Cassava Sciences and Their Forgotten DataPrimary Endpoints, Alexander Trevelyan blog entry, 9/22/2022
- Memory Games, Part II: “The Editors-in-Chief Have Retracted This Article”Primary Endpoints, Alexander Trevelyan blog entry, 9/26/2022
- PLOS ONE Pulls Five Papers Tied to Alzheimer’s Drug ControversyThe Scientist, Jef Akst, 3/31/2022
- Requests that the FDA halt the current clinical studies of Simufilam PTI-125 sponsored by Cassava Sciences NCT04388254 and NCT04994483, pending audits of 1 the publications relied on by Cassava in support of its scientific claims concerning Simufilam; 2 tRegulations.gov, created by the Food and Drug Administration
- SEC Investigating Cassava Sciences, Developer of Experimental Alzheimer's Drug; Cassava, one of best-performing U.S. stocks this year, denies claims that it manipulated research resultsMichaels, D., & Walker, J. (2021, Nov 17). SEC investigating cassava sciences, developer of experimental alzheimer's drug; cassava, one of best-performing U.S. stocks this year, denies claims that it manipulated research results. Wall Street Journal (Online) Retrieved from https://www.proquest.com/newspapers/sec-investigating-cassava-sciences-developer/docview/2598081310/se-2?accountid=14196
- Simufilam Compound SummaryPubChem
- After retractions, Alzheimer’s scientist is left cleaning up a prolific collaborator’s messThe Transmitter, Brendan Borrell, 1/9/2024
- Integrity Issues Rampant in Alzheimer's Research, Say InvestigatorsIntegrity Issues Rampant in Alzheimer's Research, Say Investigators - Medscape - March 12, 2024