Talk:Simufilam

Mechanism

From the NYT article cited on this page: "[They claim] simufilam restores the normal shape and functioning of a protein called filamin A that becomes warped in the brains of people with Alzheimer’s disease, ... But Alzheimer’s experts said they knew of no independent studies that supported this hypothesis or would explain the results."

Not a WP:MEDRS but enough to make me wary about adding the mechanism with a primary source as ref. I'll add "better source needed" for the moment; it would be nice if someone came up with a better solution. --ἀνυπόδητος (talk) 08:32, 22 April 2022 (UTC)

The first sentence under Pharmacology needs an edit: "Burns and Wang reported in 2008 ... and in 2020 that by disrupting that simufilam reduces the ultra-tight binding of amyloid beta 42..." No idea what "that" is referring to. Does not make sense. The 2008 publication is not really relevant unless the fact that simufilam also binds this site on FLNA is spelled out explicitly. Here's a suggestion:

"In 2020, Burns and Wang demonstrated that by binding FLNA, simufilam reduces the ultra-tight binding of Abeta42 to the alpha 7 nicotinic receptor."

Also this sentence is not relevant here: "Two papers unrelated to Alzheimer's disease that reported FLNA binding by certain opioid antagonists and FLNA's role in opioid tolerance and dependence were retracted for "similarities in background pixels" in western blot images without evidence of data manipulation." This section is Pharmacology of Simufilam. SighSci (talk) 18:42, 12 September 2022 (UTC)

Simufilam vs. filamin A

@Chhandama: The new additions to article seem to mix up simufilam (the small-molecule drug) and filamin A (the protein). For example:

• "The existence of simufilam as an opioid antagonist ..." – shouldn't this be filamin A? Not sure.
• "In 2010, Burns and Wang identified the protein and named it PTI-609" – PTI-609: a novel analgesic that binds filamin A to control opioid signaling says that PTI-609 binds to the protein filamin A. But is this a WP:MEDRS?
• "In 2012, their research team redescribed it as PTI-125 and reported it as a novel compound" – now this isn't about filamin A any more but about simufilam.
• "The original discovery paper claimed it as a filamin A-binding peptide of 300-kDa size." – can't be right. Filamin A is a ~300 kDa-peptide, but simufilam (260 g/mol, not a peptide) binds to filamin A.
• and probably more.

Could you look into this? -- ἀνυπόδητος (talk) 10:50, 1 May 2022 (UTC)

Thank you for pointing out. Chhandama (talk) 07:36, 2 May 2022 (UTC)

Disputes

From an edit made by user:71.41.248.226 ["(edited for accuracy)"], there are some points that may not follow Wikipedia policies on neutrality, reliable source, original research and possibly conflict of interest:

1. "The link between FLNA and Alzheimer's disease is novel and will be ultimately determined by clinical data." Speculation and original idea.
2. "...alleged research misconduct, which focused primarily on Western blot images from mostly unrelated publications as old as 2005." "Mostly" is an overstatement, 2005 paper is used as reference of data manipulations in later papers. -- This 2005 paper was found by the journal editor to have "no evidence of data manipulation" and it is unrelated to simufilam or Alzheimer's disease.
3. "...retracted for "unresolved issues" relating to "similarities in background pixels" of Western blot images, but with no evidence of data manipulation" seems to hide the fact that PLOS One retracted the two papers for unreliable data.
4. Some statements are presenting research results: "change from baseline (mean pearson's r=0.06)", "simufilam reduces tau hyperphosphorylation by preventing or disrupting filamin A's linkage to the alpha7 nicotinic acetylcholine receptor and to toll-like receptor 4", "significantly reduced from baseline after 28-day treatment". Not encyclopedic.
5. Lindsay Burns is not Senior Vice President of "Neuroscience" but of Cassava Sciences.
6. Citation removal and damage. Chhandama (talk) 06:12, 6 May 2022 (UTC)

Science article about fabrication

6-month investigation by Science provided strong support for Schrag’s suspicions and raised questions about Lesné’s research.JuanTamad (talk) 09:25, 31 July 2022 (UTC)

The Sylvain Lesné issue has no connection to this article, other than the article in Science that discussed both scandals:

• Science podcast July 22, 2022, with Charles Piller, author of Piller C (July 21, 2022). "Blots on a field?". Science. 377 (6604): 358–363. doi:10.1126/science.add9993. PMID 35862524. S2CID 250953611. Archived from the original on July 21, 2022.. SandyGeorgia (Talk) 16:23, 6 August 2022 (UTC)

Sorting primary sources

With two COI editors now blocked from this suite of articles, my attempt to sort the primary sources is at:

• Talk:Cassava Sciences/Primary sources

Perhaps some progress can be made towards cleanup. I'm not sure the chart is yet complete; still working (for example, I still have to review The New Yorker and others). SandyGeorgia (Talk) 18:36, 1 September 2022 (UTC)

Allegations of research irregularities section

This page is about simufilam. All three simufilam publications have been cleared of the allegations of data manipulation: Journal of Neuroscience, Neurobiology of Aging and Journal of Prevention of Alzheimer's Disease. The first two maintain expressions of concern to acknowledge the CUNY investigation that is still ongoing. The third is cleared with no expression of concern, but this clearance and quote can only be cited by a Cassava (August 18) press release. These other papers discussed here (those retracted) do NOT discuss simufilam or Alzheimer's disease and should be removed. SighSci (talk) 18:48, 12 September 2022 (UTC)

Those papers are part of the history of the FLNA hypothesis. SandyGeorgia (Talk) 20:33, 12 September 2022 (UTC)

They are NOT part of the history of "the FLNA hypothesis" unless you mean that FLNA is involved in opioid receptor signaling, which was also a new finding then, corroborated by one other researcher. FLNA being critical to AD pathology and the target of simufilam is NOT in those papers. Proteins are involved in many different functions, so are you going to claim that all papers about mTOR in cancer are foundational to mTOR in AD? Oh, sorry, strawman. Those two papers identified FLNA as important in opioid receptor signaling only. SEPARATELY and LATER, Dr. Wang realized that a very large protein was present when amyloid signals via alpha 7. There are not many proteins of this size, so he used some antibodies to figure out what it was. When he identified it as FLNA, Dr. Wang and Dr. Burns decided to try the FLNA-binding compounds being developed for analgesia TO SEE if they could disrupt FLNA's linkage to alpha 7. All of that is in the JNS paper that is the first and only foundational paper for simufilam. Not the JCI paper on insulin resistance as claimed by Piller, not the PLOS papers on opioid receptor signaling. I see through your intentions. Hiding that ALL three simufilam papers have been cleared, yet highlighting that these unrelated papers have been retracted -- controversially I might add. Anyone reasonable here? You should remove this entire section since NO papers on SIMUFILAM have had "irregularities" found by editors. SighSci (talk) 19:04, 20 September 2022 (UTC)

Just saw your formatting message. Therefore:

Current text: Two papers were retracted by journals and expressions of concern were issued for other papers.

Proposed text: There are three papers that discuss simufilam. No journal editor has found evidence of data manipulation, although two maintain expressions of concern to acknowledge the ongoing CUNY investigation. Editors of the third paper issued a statement released publicly by Cassava Sciences: "We do not find convincing evidence of manipulation of data or intent to mislead, and therefore take no action regarding the published paper." https://www.cassavasciences.com/news-releases/news-release-details/no-evidence-data-manipulation-science-publication-simufilam. SighSci (talk) 19:14, 20 September 2022 (UTC)

You are literally asking me to add "There are three papers that discuss simufilam. No journal editor has found evidence of data manipulation, although two maintain expressions of concern to acknowledge the ongoing CUNY investigation" ???? What secondary source supports this original research? This is very frustrating. Firefangledfeathers these requests need a new set of eyes because I am unable to decipher what SighSci wants or how to comply. Perhaps you can cut through it ?? SandyGeorgia (Talk) 19:20, 20 September 2022 (UTC)

This is an easy no from me. I need to be able to float—as if on a lazy river—on the warm water of reliable, secondary sources all the way to your preferred destination. Firefangledfeathers (talk / contribs) 19:36, 20 September 2022 (UTC)

Smile ... such a nice thought :) SandyGeorgia (Talk) 19:39, 20 September 2022 (UTC)

Why can you not cite the actual scientific papers themselves and for the two that have them, the expressions of concern that state they did not find clear evidence of data manipulation? Why are you so adverse to this? They need to be publicly discussed in the media to be mentioned? SighSci (talk) 20:42, 20 September 2022 (UTC)

I'm not adverse/averse to the change at all, but I am firmly apathetic. Help me care. You mention the expressions of concern. This would be a good time to link them, and quote the material in them that supports your recommended change. Firefangledfeathers (talk / contribs) 21:08, 20 September 2022 (UTC)

Well you should care because this section is very misleading as is. These EoCs were cited before and conveniently removed. I suspect SandyGeorgia may have her own COIs or connections to people involved in the FDA petition or trying to stop these clinical trials. She has demonstrated knowledge of another person posting on these talk pages that could only come from reading his posts on Twitter. I.e., once he disclosed his COI as a shareholder, she asked "how many shares?" How is that relevant? It's personal, but she apparently knew he was a major shareholder. She also apparently knew of his personal interest in AD, which should not itself be a COI. He follows all AD drug candidates, not just simufilam.

Two of the three journals provided statements to Cassava that were released in press releases. One did not issue any sort of editorial note. I cite both the EoCs and public statements below.

Proposed text: There are three published papers on simufilam. https://pubmed.ncbi.nlm.nih.gov/22815492/, https://pubmed.ncbi.nlm.nih.gov/28438486/, https://pubmed.ncbi.nlm.nih.gov/32920628/. No journal editor found evidence of data manipulation. The Journal of Neuroscience stated "No evidence of data manipulation was found for Western blot data." https://www.cassavasciences.com/news-releases/news-release-details/no-evidence-data-manipulation-science-publication-simufilam, but issued an erratum https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672690/ and an expression of concern pending results of the CUNY investigation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802929/ Neurobiology of Aging stated, "Overall, the editors did not find compelling evidence of data manipulation intended to misrepresent the results" but is also maintaining an expression of concern until the CUNY investigation concludes. https://www.sciencedirect.com/science/article/pii/S0197458022000562?via%3Dihub. Editors of the third paper issued a statement released publicly by Cassava Sciences: "We do not find convincing evidence of manipulation of data or intent to mislead, and therefore take no action regarding the published paper." https://www.cassavasciences.com/news-releases/news-release-details/no-evidence-data-manipulation-science-publication-simufilam SighSci (talk) 18:07, 22 September 2022 (UTC)

That's enough for me; with these bad faith allegations, you should be blocked, and I'm done trying to help out here ... unwatching the lot, good luck trying to find someone to help, please don't ping me back to this suite of articles, as I've had enough abuse. SandyGeorgia (Talk) 19:05, 22 September 2022 (UTC)

Retractions unrelated to Simufilam should be removed

These papers are unrelated to Simufilam and this sentence should be removed.

Two papers unrelated to Alzheimer's disease that reported FLNA binding by certain opioid antagonists and FLNA's role in opioid tolerance and dependence were retracted for "similarities in background pixels" in western blot images without evidence of data manipulation.

The expressions of concerns are also redundantly mentioned in the Allegations of research irregularities section. Same point the Opiod papers are unrelated to Simufilam so the retraction mention should be removed.

Two papers were retracted by journals and expressions of concern were issued for other papers.[27]

Mnachtrab (talk) 10:59, 11 October 2022 (UTC)

The cited NY Times article indicates that they're related, We can't overrule the judgment of the sources. MrOllie (talk) 23:01, 12 October 2022 (UTC)

They are related to the company but not to the drug Simufilam. You guys are conflating the two development processes into one just like the NY times article did. Put those on the Remoxy page not on here. I think all the "controversial" topics about the drug should be organized in the allegations of research irregularities. Why does it have to be told throughout. There are great sources that have followed their journey over the years that show the development timeline of the drug that are WAY more credible than the new york times in medical research. Here is one that has done a good job covering the actual story:

https://alzheimersnewstoday.com/pti-125/

I think the page should be similar to that, then put the allegations in their own section.

Mnachtrab (talk) 01:04, 13 October 2022 (UTC)

just like the NY times article did Yes, that is what we are supposed to do. We follow the reliable sources, we do not overrule them because we personally think we know better. then put the allegations in their own section. No, that is not going to happen. See WP:STRUCTURE. - MrOllie (talk) 01:12, 13 October 2022 (UTC)

CP discussion

The CP discussion in the main cassava wiki page changed the wording away from the wording in the simufilam article. This Simufilam page says:

"The US Food and Drug Administration received a citizen petition in August 2021 to stop the clinical trials. Other scientists have also questioned the preclinical results, citing the small sample size, alleged methodological flaws in an in vitro technique, alleged manipulations of western blot images and potential conflict of interest. After the FDA declined to act on the citizen petition as investigation is not within their purview..."

Declined to act is not what they did. The CP was rejected by the FDA... Please review the references to the CP in the cassava page and change the language to reflect what SandyGeorgia edited there after reviewing that language... or just reference the CP with NEUTRAL language and point readers to the other page.

A citizen petition attempting to suspend the clinical trials was rejected by the Food and Drug Administration (FDA) in February 2022. Cassava Sciences has denied any wrongdoing and raised concerns about the motivations behind the FDA petition. Mnachtrab (talk) 11:19, 18 October 2022 (UTC)

@Mnachtrab: You have been told numerous times about how to format edit requests yet are still failing to follow the instructions. I have tweaked the text slightly to match the Reuters source more closely, but there is nothing in there about the petition being rejected or declined. SmartSE (talk) 12:52, 18 October 2022 (UTC)

What is wrong with the format of request? Can you please be more respectful?

-Matt Mnachtrab (talk) 15:54, 19 October 2022 (UTC)

To be clear, I am saying the cassava wiki page. It is phrasing what happened with the CP different than the simufilam page. I am suggesting the simufilam page use the same language or just refer to the Cassava wiki page. Mnachtrab (talk) 00:27, 20 October 2022 (UTC)

They don't need to match exactly. But supposing they did, why would we not make Cassava Sciences match this one rather than the other way round? MrOllie (talk) 00:31, 20 October 2022 (UTC)

In fact, I've gone ahead and moved Cassava Sciences closer to the wording of the source as well. MrOllie (talk) 00:37, 20 October 2022 (UTC)

Build out the Clinical Trial Phases of Simufilam

IN PROGESS - SAVING WHILE I BUILD - FEEL FREE TO DO REPLIES AND LET ME KNOW WHAT YOU THINK OF THE PROJECT

To interested parties: Simufilam (PTI-125) have a long history of development that has gone through many stages from clinical to phase 3. I know other editors have called out that i have a point of view or COI, but I did some work to gather information for the whole history sighting actual sources (journal article, clinicaltrials.gov and company filings) secondary sources if it has been written about. I propose we use a format/layout that is like this page: https://en.m.wikipedia.org/wiki/Phases_of_clinical_research

This is a pretty large suggested change to the page, so I welcome feedback on how to implement it. I don't mind doing the work and formatting to get it in final form on the main page then removing my edit rights after it's done. Or if there is a good way to do a large edit somewhere else i can do it there then insert after we agree on content. This is all fact based non-controversial. Just the history of the drug.

Extended content collapsed
The following discussion has been closed. Please do not modify it.
Summary of Simufilam Phases of Clinical Research Cassava Science performed preclicial work with Hoau-Yan Wang at CUNY. After preclinical research, they created a clinical trial strategy utilizing small early studies on a broad panel of biomarkers to detect if Simifulam could impact any biomarkers associated with Alzheimer’s disease pathology. The small phase 2 studies were used to inform a larger open label prior to a large and expensive phase 3 trial. Summary of clinical trial phases Phase Title Dose Patient monitor Sites Number of participants Results/Notes Preclinical Reducing Amyloid-Related Alzheimer's Disease Pathogenesis by a Small Molecule Targeting Filamin A PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis In Mice: 10 mg/ kg PTI-125 (ICV) On human brain tissue: 0.1nm PTI-125 on Native AD Tissue;  1 nm PTI-125 on  Aβ42-incubated control tissues In mice: 30mg/kg/d of PTI-125 (Oral) On human brain tissue: PTI-125: (1 pM-1nM) with 0.1 mM Ab42. Scientific researcher No human subjects Efficacy shown with a safety adanvate Phase I A Safety Study of PTI-125 in Healthy Volunteers Drug: 50 mg PTI-125 Oral Solution Drug: 100 mg PTI-125 Oral Solution Drug: 200 mg PTI-125 Oral Solution Drug: Placebo Oral Solution Clinical researcher 1 24 healthy participants Safe and well tolerated and the drug showed potential effectiveness [4] Phase 2a PTI-125 for Mild-to-moderate Alzheimer's Disease Patients Drug: 50 mg PTI-125 Oral Tablet Drug: 100 mg PTI-125 Oral Tablet Drug: Placebo Tablet Clinical researcher 2 13 participants with Alzheimer’s Disease Safe and well tolerated. showed Total tau, neurogranin, and neurofilament light chain decreased by 20%, 32% and 22%, respectively [3] Phase 2b PTI-125 for Mild-to-moderate Alzheimer's Disease Patients Drug: 50 mg PTI-125 Oral Tablet Drug: 100 mg PTI-125 Oral Tablet Drug: Placebo Tablet Clinical researcher 9 64 participants with Alzheimer’s Disease The drug was safe and well tolerated. The drug showed evidence of disease-modifying effects with statistical significant improvement in total-tau, P-tau, amyloid beta-42, Proinflammatory IL-6, and many other biomarkers associated with Alzheimer’s disease pathology [9] Phase 2 Open Label Safety Study Open- label Simufilam (PTI-125) for Mild-to-moderate Alzheimer's Disease Patients with 6-month randomized withdraw Drug: 100 mg PTI-125 Oral Tablet Clinical researcher 17 200 participants with Alzheimer’s Disease Study is not complete.  Interim results indicate the drug is safe and well tolerated. Phase III (REFOCUS-ALZ) A 76-week safety and efficacy study of simufilam (PTI-125) Drug: 50 mg PTI-125 Oral Tablet Drug: 100 mg PTI-125 Oral Tablet Drug: Placebo Tablet Clinical researcher 79 1083 participants with Alzheimer’s Disease N/A Phase III (RETHINK-ALZ) A 52-week safety and efficacy study of simufilam (PTI-125) Drug: 100 mg PTI-125 Oral Tablet Drug: Placebo Tablet Clinical researcher 76 750 participants with Alzheimer’s Disease N/A Phase III Open Label Multi-national, multi-center, fixed-dose, 52-week, open-label extension study Drug: 100 mg PTI-125 Oral Tablet Clinical researcher 150 1600 participants with Alzheimer’s Disease N/A Preclinical simufilam (formally PTI-125) Research Type Intervention Outcomes/Results In vivo animal study Mice received ICV infusion of 4.8 nmol Aβ42 or vehicle (10% DMSO) daily for 1 week followed by 10 mg kg–1 PTI-125 daily for 2 weeks. Aβ42 mice treated with PTI-125 showed decreased amyloid deposites on immunostained Aβ42 aggregates and suppression of phosphorylation of tau at all three phosphorylation sites. Postmortem human brain tissue Frontal cortex from control subjects was incubated with 0.1 μm Aβ42. To test the effects of PTI-125 on Aβ42-incubated control and native AD tissues, PTI-125 (0.1 and 1 nm) was added  on native AD tissues and Aβ42-incubated control tissues for 1 hours incubation time afterward. AD brains showed elevated levels of filamin A bound to the α7 nicotinic receptor. Incubation of brain slices with PTI-125 reversed this association, and also reduced the amount of Aβ42 bound to the receptor. In vivo animal study To assess the effect of in vivo PTI-125, Four- and 8-month-old male and female E129 mice and 3xTg AD mice received 30mg/kg/d of PTI-125 HCl (22 mg/kg/d free base equivalent) orally via drinking water for 2 months. Mice postmortem brain tissues showed PTI-125 reduced receptor dysfunctions and improved synaptic plasticity, with some improvements in nesting behavior and spatial and working memory in 3xTg AD mice. Tissues also demonstrated reduced tau hyperphosphorylation, aggregated Ab42 deposition, neurofibrillary tangles, and neuroinflammation. Postmortem human brain tissue To test the ex vivo effects of PTI-125 on Ab42-incubated control and native AD tissues, PTI-125 (1 pMe1 nM) was added simultaneously with 0.1 mM Ab42. Incubation continued for 1 hour in the dark.5 Human brain tissues showed PTI-125 restored receptor function, improved synaptic plasticity and reduced tau hyperphosphorylation.Efficacy in postmortem AD and Ab42-treated age-matched control hippocampal slices was concentration-dependent starting at 1 picomolar (pM) concentration.5 In vivo animal study Metabolic stability was characterized in mouse, rat, dog and human hepatic microsomes.PTI-125 (1 µM) was incubated with mouse, rat, dog, and human liver microsomes (1 mg/mL) at 37°C for 0, 15,30 and 60 minutes in the presence of NADPH (1 mM). The remaining PTI-125 concentrations were quantitated by liquid chromatography tandem mass spectrometry (LC-MS/MS). PTI-125 was metabolically stable in human liver microsomes, showed no inhibition or induction of CYP enzymes, and had mild inhibition of OAT1, OCT1/2 and MATE1. PTI-125 is unlikely to have drug-drug interactions clinically.6 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621293/; Novel Drug Knocks Aβ Off Synapses, Reduces Toxicity | ALZFORUM 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541970/ 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621293/ 4 https://www.alzforum.org/news/research-news/novel-drug-knocks-av-synapses-reduces-toxicity 5 PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis - PubMed (nih.gov) 6 LuoISSX19-PTI-1125.pdf (labcorp.com) PTI-125 Phase 1 Study Description:  This is a Phase 1 study to evaluate the safety profile of PTI-125 in healthy volunteers.  Single center, randomized, double-blind, placebo controlled, SAD study of three escalating doses of PTI-125. A total of 24 healthy subjects enrolled in one of three dose cohorts. Each cohort will contain 8 subjects; six receive PTI-125 and two receive placebo. Three SAD does of PTI-125 oral solution (50, 100 or 200 mg) or placebo solution will be administered [5]. Results:  The drug showed to be safe and well tolerated and the absence of dose-limiting effects did not show evidence increases in treatment dose causes problems.  Additionally, the drug showed potential effectiveness because it was absorbed by the patients bodies rapidly [4].   PTI-125 Phase 2a Study Description:  This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate AD patients, 50-85 years of age. A total of twelve (12) patients will be enrolled into the study. Patients will receive 100 mg b.i.d. of PTI-125. The objectives of this study are to investigate the safety, pharmacokinetics and effect on biomarkers of PTI-125 following 28-day repeat-dose oral administration [2]. Results:  The drug had no drug-related adverse events in the study.  As published in The Journal of Prevention of Alzheimer's Disease, the study results showed Total tau, neurogranin, and neurofilament light chain decreased by 20%, 32% and 22%, respectively [3]. PTI-125 Phase 2b Study Description:  Randomized, placebo-controlled clinical trial that enrolled 64 people with mild to moderate Alzheimer’s.  Participants were randomly assigned to receive either 50 mg or 100 mg oral tablets of simufilam, or a placebo, twice a day. The objective was to assess if the treatment lowered levels of Alzheimer’s-related biomarkers in participants’ cerebrospinal fluid in 28 days [7] Results:  The drug was safe and well tolerated.  Initial results indicated there were not significant differences between the treatment and placebo group [6], but upon review the researchers found there was significant variation in biomarker reading in the placebo group so the samples were reanalyzed [8].  Upon reanalysis of Simufilam (formerly PTI-125) phase 2b results, it was found to improve many Alzheimer Disease biomarkers.  The drug showed evidence of disease-modifying effects with statistical significant improvement in total-tau, P-tau, amyloid beta-42, Proinflammatory IL-6, and many other biomarkers associated with Alzheimer’s disease pathology [9]. Phase 2 Open Label Safety Study Description:  In progress work Results:  In progress work Phase III  (RETHINK-ALZ) Description:  A 52-week safety and efficacy study of simufilam (PTI-125) given twice daily to participants with mild-to-moderate Alzheimer's disease (AD) for 52 weeks. Approximately 750 participants will be randomized (1:1) to receive either placebo or 100 mg tablets of simufilam, twice daily, for 52 weeks. Clinic visits will occur 4 weeks after the baseline visit, and then every 12 weeks until the end of the study. The safety of simufilam, and its efficacy in enhancing cognition and slowing cognitive and functional decline will be evaluated [10] Phase III  (REFOCUS-ALZ) Description: A 76-week safety and efficacy study of simufilam (PTI-125) given twice daily to participants with mild-to-moderate Alzheimer's disease (AD) for 76 weeks. Approximately 1083 participants will be randomized (1:1:1) to receive either placebo, 50 mg tablets of simufilam, or 100 mg tablets of simufilam, twice daily, for 76 weeks. Clinic visits will occur 4 weeks after the baseline visit, and then every 12 weeks until the end of the study. The safety of simufilam, and its efficacy in enhancing cognition and slowing cognitive and functional decline will be evaluated.[11] Phase III  (Open-label Extension for Phase 3 Clinical Trials of Simufilam) Description: This is a multi-national, multi-center, fixed-dose, 52-week, open-label extension study. After completing participation in either RETHINK-ALZ (PTI-125-06) or REFOCUS-ALZ (PTI-125-07), subjects will have the option to participate in this study. After the subject provides consent and the Investigator confirms the subject satisfies both inclusion and exclusion criteria, the study drug will be administered at the research site on Study Day 1 and subsequent visits will be scheduled. We anticipate up to 1600 subjects may enroll in this study. Approximately up to 150 clinical sites in the USA, Canada, South Korea, and Australia will have the option to participate in this collaborative research effort. For subjects electing to participate, the clinical and laboratory assessments from the Week 76 (REFOCUS-ALZ) or Week 52 (RETHINK-ALZ) End-of-Treatment visit will serve as Baseline Visit assessments for the open-label study on Study Day 1. All subjects will return in 4 weeks and every 12 weeks thereafter for safety assessments. At all post-baseline visits, subjects will report any adverse events since their last visit. In addition to adverse event monitoring, safety will be evaluated at every visit by vital signs, brief examinations, clinical laboratory tests (biochemistry, hematology, and urinalysis) and the Columbia Suicide Severity Rating Scale (C-SSRS). Study drug use since the last visit will be assessed and a new bottle of study drug will be dispensed. The emerging subject safety assessments will be monitored throughout the study by an independent Data Safety Monitoring Board (DSMB).[12]

Mnachtrab (talk) 13:47, 18 October 2022 (UTC)

This level of detail is far, far too much for a Wikipedia article. That seems to be an artefact of overuse of primary sources and other stuff that doesn't meet WP:MEDRS such as these alzheimer's news sites. I would oppose any inclusion like this. - MrOllie (talk) 14:04, 18 October 2022 (UTC)

Yes I agree. SmartSE (talk) 14:09, 18 October 2022 (UTC)

Stat news

I have the full text from Stat, which says no more effective than placebo.

• https://www.statnews.com/2023/01/24/new-results-show-cassavas-alzheimers-drug-has-placebo-like-efficacy/

SandyGeorgia (Talk) 16:37, 28 January 2023 (UTC)

SG, how usable do you think the source is for a statement about drug effectiveness? It looks like a reputably published blog/column. Good enough for wikivoice? With attribution? Judging just by the preview. Firefangledfeathers (talk / contribs) 17:49, 28 January 2023 (UTC)

Firefangledfeathers: While the author goes into good detail comparing early results to later, he also expresses strong opinions on the topic, so although the Stat (website) meets reliability in spades, it is filed under "Adam's take", so I would err on the side of caution and attribute the statement, rather than use Wikivoice. Let me know if I should email you a copy. SandyGeorgia (Talk) 18:07, 28 January 2023 (UTC)

Stat directly contradicts the quote of the statistician

Stat claimed that "well outside the historical range for placebo responses from numerous other studies" means placebo-like. That statement clearly shows a conflict. And Stat did not comment on the July article, which was placebo-controlled. Subicculum (talk) 16:51, 2 August 2023 (UTC)

Please quote the FDA docket precisely

"not a proper avenue" means the petitions did not bring any evidence but asked for the shut down to follow an FDA investigation to find any facts that could not be provided. This is indeed a proper avenue if there had been evidence. The actual quote is that the "petitions do no purport to set forth all factual information. Rather, you call on FDA to initiate an investigation and fact-finding process." Why was this more accurate and precise quote removed? Subicculum (talk) 17:04, 2 August 2023 (UTC)

This quote is from Reuters. It is preferable to quote a secondary source such as this rather the primary source of the FDA letter. The journalist has read the primary source and interpreted it for us. SmartSE (talk) 17:51, 2 August 2023 (UTC)

Yet it is misleading and intentionally vague to fit the storyline of the Reuters article. Why not clarify? Subicculum (talk) 21:55, 2 August 2023 (UTC)

Controversy about this article: request for comment

The drug simufilam is highly controversial. Some people think the company is engaged in criminal behavior and the drug is a scam. Others think that stock short sellers are profiting off of deliberately tanking the stock. I would like to see this controversy represented more evenly, with a neutral point of view. I am not saying which side is right--just that the article is unbalanced and some people seem to be enforcing a one-sided view. Disclosure: I know Lindsay Burns personally. Asbruckman (talk) — Preceding undated comment added 21:47, 2 August 2023‎ (UTC)

• Asbruckman, my experience with RfCs tells me this one is unlikely to be productive. There hasn't been a thorough discussion of the issues here, as required by WP:RFCBEFORE, and the RfC question itself is too broad to result in actionable consensus. I recommend removing the RfC tag and proceeding with local discussion. Firefangledfeathers (talk / contribs) 22:11, 2 August 2023 (UTC)

  Discussion here (two COI editors blocked, the connection to Lindsay Burns if of interest, as other friends have weighed in re her article, lots of marginal press release churnalism used as sourcing in past versions). The faulty "RFC" gives no new sources. So what exactly are we RFCing about ? SandyGeorgia (Talk) 22:32, 2 August 2023 (UTC)

  The issue of balance is about three pages: this one, Cassava Sciences company, and Lindsay's own page. I have absolutely no opinion on who is right. I just think the pages take a strong opinion in one direction, violating NPOV.

  I am an acquaintance of Lindsay's, not a friend. We've talked for about five minutes twice in the last 40 years. I'm not sure if I am allowed to make any edits here or not. I would prefer to stay out of it, but I'd like to see the pages more balanced. We will all know the truth when their clinical trials are further along, and until then it would be nice to be more circumspect about it?

  Do people agree that this isn't a rock-solid one-sided situation? I think we need to address that question before we can move forwards.

  Asbruckman (talk) 00:01, 3 August 2023 (UTC)