Straws are discrete research notes that relate to a particular aspect of the company. Grouped under #hashtags, they are ranked by votes.
A good Straw offers a clear and concise perspective on the company and its prospects.
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Leqembi (Lecanemab) just approved by FDA.
Likely full approval for Eisai’s Leqembi next month after FDA decision this Friday. Predicted CMS coverage. Anticipated sales of US $7billion by 2030.
For those of you interested in Donenemab by Eli Lilly: see below. Certainly looks like a better treatment option as less frequent dosing.
https://endpts.com/lillys-alzheimers-drug-donanemab-succeeds-in-phase-iii-trial/
Esai will face increasing FDA scrutiny on June 9th over the death of a patient in a Lecanamab extension study.
Possible stricter drug labeling may be needed for patients with certain genetic markers. This would go a step beyond avoiding prescriptions in patients on blood thinners. The amyloid stripping nature of the drug my thin and weaken blood vessel walls in vulnerable patients leading to brain bleeds.
Never straight forward in the Alzheimer’s drug world.
https://www.cogstate.com/clinical-trials/therapeutic-focus-areas/parkinsons-disease/?cn-reloaded=1
As seen on Linked in another large area of research with new plasma drug treatment trials for Parkinson’s. Cogstate is involved in clinical drug trials to test for cognitive impairment for this disease. Another large market opportunity.
https://www.nytimes.com/2023/01/06/health/alzheimers-drug-leqembi-lecanemab.html
Interesting article suggesting with this approval Lecanemab is likely to be given Medicare approval.
I thought this was a very interesting addition to labelling:
“The Leqembi label says the drug should be used only for patients in early and mild stages of Alzheimer’s disease, matching the status of patients in the clinical trials of the drug. It instructs doctors not to treat patients without doing tests to confirm that they have one of the hallmarks of Alzheimer’s: a buildup of the protein amyloid, which Leqembi (like Aduhelm) attacks.”
Which cognitive tests are not stated. Perhaps an Opportunity for Cogstate here.
FDA has granted accelerated approval for Lecanamab.
This drug provides hope for treatment of Alzheimer’s rather than just purely treatment of disease symptoms. Patients appear to have a reduction in Amyloid plaque vs placebo. Based on the amyloid plaque theory this should reduce cognitive decline.
This likely hales the first of many new treatments for Alzheimer’s to hit the market. Suggesting a healthy level of future clinical trial work for Cogstate. Whether this extends to at home or community cognitive testing is yet to be seen. Overall good news for the company.
https://www.biopharmadive.com/news/eisai-biogen-alzheimers-lecanemab-trial-results-positive/632570/
More articles with more details. An approval date target for Lecanemab with the FDA, sited as March 2023 (see above).
After Alduhelm this will be scrutinized closely - the note about ARIA below is interesting:
“The imaging abnormality, known as ARIA, occurred in 21% of patients treated with lecanemab and 9% of those on placebo. About 3% of patients on lecanemab patients had symptomatic ARIA with swelling in the brain, and 0.7% had symptomatic ARIA with micro-bleeding.”
What the FDA will make of these known side-effects of these type of Alzheimer’s drugs will be crucial for Lecanemabs approval target.
“Amyloid-related imaging abnormality (ARIA) is a known class side effect of antibodies like Aduhelm that target amyloid plaque in the brain. Its most common form, a type of cerebral edema called ARIA-E, can be associated with headache, confusion, nausea and gait disturbances, among other symptoms.23 Aug 2021” (https://www.clinicaltrialsarena.com/analysis/aduhelm-safety/)
FDA will need to see pretty convincing efficacy and safety data. But possibly a very exciting moment for Alzheimer’s sufferers and their families.
#Alzheimer’sresearchfraud?
The controversy in the Alzheimer’s space just keeps coming. We are all familiar with the recent Alduhelm drug disaster (discussed in previous straws). Last month Gentech’s new Alzheimer’s drug contender Crenezumab also failed to slow cognitive decline in human subjects despite promise in its early animal studies.
The failure of all these drugs may have a route cause as they are all designed to target amyloid plaques. However the foundational research in Amyloid plaque theory published in Nature in 2006, that these drugs are based on, is likely fraudulent. (1,2)
News broke over the weekend across multiple publications sighting alleged research fraud by a seminal researcher team in the Alzheimer’s space. 90% of potential Alzheimer’s drug treatments were based on the Amyloid plaque theory that stemmed from this original work. Most Alzheimer’s drugs have aimed to target and stop these amyloid plaques which were thought to be the cause of cognitive decline.
“It’s not unusual for drugs that are effective in vitro and in animal models to turn out to be less than successful when used in humans, but Alzheimer’s has a record that makes the batting average in other areas look like Hall of Fame material.” (1)
“In 2006, Nature published a paper titled “A specific amyloid-β protein assembly in the brain impairs memory.” Using a series of studies in mice, the paper concluded that “memory deficits in middle-aged mice” were directly caused by accumulations of a soluble substance called “Aβ*56.” This was a specific form of a group known as “toxic oligomers” that had long been suspected as the possible precursors of amyloid plaques. The paper then went on to directly connect that condition to “cognitive deficits associated with Alzheimer's disease” independently of other conditions affecting the aging brain. “ (1)
Professor Lesne and Dr. Karen Ashe were 2 of the main contributors to the Nature paper.
“Not only has it been cited hundreds of times in other work, roughly 100 out of the 130 Alzheimer’s drugs now working their way through trials are directly designed to attack the kind of amyloids featured in this paper. “ (1)
Professor Matthew Schrag from Vanderbilt university began to investigate the failure of Simufilam one of the early amyloid drugs developed by Cassava Sciences. Upon digging further into the original Lesne paper he discovered that
“Images in the paper that were supposed to show the relationship between memory issues and the presence of Aβ*56 appeared to have been altered.”
“molecular biologist Elisabeth Bik said of the paper, “The obtained experimental results might not have been the desired results, and that data might have been changed to … better fit a hypothesis.” (1)
“He said in a Science article that he and other reviewers have identified as many as 10 papers on the protein that deserve deeper scrutiny. The report also cited other prominent researchers who have had difficulty replicating results of the studies on the specific proteins.” (2)
This has huge ramifications for Alzheimer’s research. Pharmaceutical companies have already ploughed billions of dollars into drug development. Futhermore:
“Since that 2006 publication, the presence or absence of this specific amyloid has often been treated as diagnostic of Alzheimer’s. Meaning that patients who did die from Alzheimer's may have been misdiagnosed as having something else. Those whose dementia came from other causes may have falsely been dragged under the Alzheimer’s umbrella. And every possible kind of study, whether it's as exotic as light therapy or long-running as nuns doing crossword puzzles, may have ultimately had results that were measured against a false yardstick.”(1)
It will be interesting to see whether there is a knock on affect for Cogstate shares this week. This news does not portend well for Biogen’s new drug in development Lecanemab. If the science that it has been developed on can’t be trusted the likelihood of success seems slim to none.
A reminder of why I chose to invest in the picks and shovels approach in this controversial area of research.
Cheers
Nnyck
2. https://www.theguardian.com/society/2022/jul/23/alzheimers-study-fraudulent
Eisai’s Lecanemab pushing through with Phase III. Seems to be more effective at clearing Amyloid than its predecessor Alduhelm. Large scale double blind study commencing. Lots of people using Cogstate tools.
See below for latest news:
The jury is in folks CMS to only reimburse Alduhelm and other amyloid targeting drugs for patients in clinical trials. This will effect Biogen and it’s competitors are on notice. Finding an Alzheimer’s drugs path to profitability will need a rejig by these companies. So FDA accelerated approvals now seem moot. As CMS will need hard clinical evidence from lengthy trials to reimburse Pharma companies. As expected appeals have been launched.
My take Cogstate will still be needed and possibly for longer contracts with these companies. It doesn’t seem likely any of the big names will cease pursuing an effective Alzheimer’s treatment.
“Shunned by independent experts and a whole swath of physicians who treat Alzheimer’s, longtime skeptic Brian Skorney at Baird now calls the Biogen drug Zombiehelm. And no manner of necromancy can revive it. The first approved drug for Alzheimer’s, what was always considered the Golden Ticket in drug R&D with a multibillion-dollar payout, is commercial waste.” (2nd Endpoints article sighted below)
“For Biogen, there is only one way out: Produce solid clinical data that its other drug allied with Eisai, lecanemab, can actually help patients.” (2 nd Endpoints article sighted below)
“CMS has made it very clear that it wants solid, positive clinical data on an Alzheimer’s drug before it’s covered by Medicare — making CMS the ultimate decision-maker for Roche, Eli Lilly, Biogen and anyone else looking to make marketing hay in Alzheimer’s.” (2nd Endpoints article sighted below) .
https://endpts.com/what-did-we-learn-from-biogens-cms-slap-down-data-rule/
Scathing remarks regarding FDA an Biogen’s handling of Alduhelm out on the 4/4/2022 in Endpoints.
It doesn’t get more candid then this statement:
“Biogen and the FDA dropped an unfinished, undertested, potentially unsafe product, without evidence of benefit, on a vulnerable American public, as if to say, “We’re done here, you deal with it”.”
Lilly has written its appeal to the Centre of Medicare and Medicaid Services (CMS) in a 22 Page letter see full version in Endpoints article written by Max Gelman (link below)
Lilly is appealing for their lines of drug development not to be treated with the same harsh measures applied to Alduhelm. At the very least Lilly has asked that new Alzheimer's drugs be treated on a case by case basis. They certainly look like they are making a strong case:
Another reason I like the picks and shovels approach with my CGS investment.
These CMS changes certainly look set to impact Alduhelm meaning extra expense for Biogen with further trials. The exact impact is still uncertain and could mean a delay of years before any commercial revenue for this drug. It certainly is one way to attempt to interfere in the FDA Alduhelm approval decision.
Cogstate will still get paid.
It is also unclear if the CMS decision has any impact on upcoming Alzheimer’s drugs such as Eli Lilly’s donanemab or Biogen’s lecanemab.
Read below for full details:
The pick’s and shovels approach is looking preferable right now compared to direct drug investment. The added news this week that CGS also has a revenue stream planned with Eisai’s Cogmate deal is a comfort for investors. The CMS news certainly has not impacted this weeks share price.
Cogstate Media Release
#Cogmate #ReleaseinTawain&HongKong
Cogstate released an article Jan 12 2022 – announcing it’s global commercial partner Eisai Co., Ltd will be releasing Cogstate technology directly to consumers in Tawain and Hong Kong. There is a planned release in Singapore shortly. The product has been branded ‘Cogmate’ in these markets.
Cogmate is a multi-lingual version of NouKNOW (Japan) – a digital tool for the self-assessment of brain performance. This tool is developed and distributed by Eisai using Cogstate Brief Battery (CBB).
This tool non-medical tool is designed to enable regular assessments of brain health. Results are provided immediately via the Brain Performance Index. Results plus lifestyle advise will be offered by this tool.
Eisai states it’s goal is to create an ecosystem to prevent dementia and support those living with dementia via pharmaceuticals.
Clinical trials are still marketed independently by Cogstate.
You can read further below:
In a further Interesting article posted by Endpoints:
Eli Lilly and Eisai’s Alzheimer’s drugs – Which Cogstate has deals with for clinical trials are touted to be some of the biggest potential grossing drugs to watch for in 2022. Lilly’s potential Alzheimer’s drug donanemab is expected to be one of the top two highest revenue earners with $4.5Billion in sales in 2026. Donanemab still has several ongoing Phase III clinical trials.
Eisai’s and Biogen’s other Alzheimer’s drug lecanemab is expected to bring in $1.68 billion.
Biogen yesterday confirmed that there is an investigation underway into the death of an Alduhelm trial participant.
It is widely acknowledged that Alduhelm has an image problem and the roll out of this drug has been terribly limited.
There is very slow uptake of Alduhelm infusion. Doctors are only treating very mild cognitive impairment or early Alzheimer’s.
Cognitive tests are used for eligibility in clinics that use Alduhelm infusion. Then clinics determine an MRI follow up schedule following treatment to track safety.
Alduhelm has been linked to cases of ARIA (amyloid related imaging abnormality) This is a type of brain swelling that can be detected on MRI. Although there may be no side effects initially it has been linked to nausea, gait disturbances, confusion and headache.
Hopefully with two new drugs in this class about to be released, Alzheimer’s treatment controversy will die down and it’s treatment efficacy will hopefully be established.
Eli Lilly and AC Immune (swiss biotech) dump one of their latest in house anti-tau Alzheimer’s programs. Their potential drug candidate ACI-3024 missed the primary endpoint in a Phase II study. Proving once again the challenges of anti-tau drugs for Alzheimer’s and how hard this path is to get drugs to market.
The $2billion partnership deal between Eli Lilly and AC immune is still intact despite this new revelation. Endpoints news first reported the cessation of the ACI-3024 program on Thursday. The ACI-3024 was touted as one of the drugs at the centre of the partnership deal. Eli Lily was an ideal partner for developing this drug and getting it to market. AC Immune’s press release hints that the drug may have ‘exceeded’ target drug concentrations of ACI-3024 in the CSF of trial patients based on data from animal studies.
This comes in the same week as Eli Lilly begun its new FDA submission for another amyloid targeting program for its drug donanemab. Which we have all been hearing about through our Cogstate research.
A second Alzheimer’s drug failure from Eli Lilly was also announced recently. The anti-tau antibody drug zagotenemab failed in a recent Phase II study.
The recent developments for Eli Lilly highlight how challenging getting an FDA approved Alzheimer’s drug to market really is.
#Alduhelm #controversy
The Alduhelm controversy continued. There is a very slow uptake of the drug.
Will be interesting if this turns around. Seems like the market is demanding efficacy data before recommending a drug with this hefty price tag.
Microcap Leadership Summit Thoughts #Future #Competitors #Moats
Thanks @UncleWally and @mkkle for linking this youtube clip. Really enlightening.
It was great to hear from Brad O’conner CEO he is a good presenter.
There has been quite a bit of discussion around competitors in the straws lately. I was very pleased to have the question asked about CANTAB directly to the CEO. I believe @mkkle stated that this company just wasn’t a competitor. I respectfully disagree as it has a validated computerised test that could be a potential competitor in the health care assessment space.
It was good to hear from the horse’s mouth. Brad acknowledged that Cogstate is currently in a “land grab” for its Health segment test. The aim is for Cogstate to become the dominant player with a big push and hopefully first mover advantage.
Brad states that separating yourself from competitors (33:00 minutes in) is more about marketing. Having the better test or more valid test is not necessarily going to ensure that you are the leader. He states that Cogstate’s advantage say over CANTAB is in its partnership with current pharmaceutical companies supporting sales and marketing. These companies have a vested interest in identifying people in the population who may need their alzheimer’s products through these at home self-assessment tests.
Another excellent question was asked during the Q & A about Cogstates Moat. What stops a free self-assessment app from coming in and grabbing huge chunks of ‘land’?
Ultimately new tests will not be able to make any claims about the tests sensitivity over time. Cogstate has had its test validated and sensitivity confirmed across 20-30 years. You need to follow patients for this amount of time to ensure that the test actually can pick up cognitive changes and decline. I believe this was an excellent confirmation of MOAT.
First mover advantage will be huge as initial testing compares patients to a normative database however future tests compare an individual’s results against their own baseline. This makes cognition tests highly sensitive for change. There is a huge cost to switching cognitive tests mid-stream as you would lose all your baseline cognitive function levels as tests will not be inter-changeable.
Cogstate Future
Brad confirms that the biggest revenue opportunities are currently with Alzheimer’s identification and diagnosis. Follow up revenue will come from ongoing testing of cognition. This will likely be done annually.
Interestingly Brad identifies a huge potential secondary future revenue stream in the form of data commercialisation. Eisai and Cogstate jointly own all the data from the cogstate tests. This could be de-identified and sold on to say insurers to get a better understanding of Alzheimer’s disease rates in the population.
Currently the CEO appears very focused on growth and business execution. He acknowledges that they will keep a potential NASDAQ listing on the cards for the future.
Interesting that there is a tight registry and few retail shareholders which might help to mitigate SP volatility.
Excellent share Strawpeople
Thanks
Nnyck777
Cogstate
#Competitors #Future #Thebillgatesofitall #Controversy #FinallybitthebulletIRL #Darnsharepricerisepreentry
What an interesting week for Cogstate. Thanks for posting the Bill Gates clip this week @mkkle and @bjbart. Interesting that Cogstate was named.
I am not sure whether it is all the Strawman community jostling for shares, creating the price spike this week – or Bill has let the cat out of the bag…..Jeez keep it under wraps Bill!
When one of the biggest tech entrepreneurs comes sniffing around a company it is likely people take notice. The Microsoft guru is possibly seeing dollar signs and potential. There is a goldmine in it for the first company to crack the first valid at-home cognitive test on a mobile or computer.
The global pandemic has led to the resultant rise in interest and forced administration of online cognitive testing. Researchers also warn that some of the current online and phone administered cognitive tests are by no means the best or most valid tools to be using and diagnostic accuracy should not be assumed.
Upcoming 2020 Cochrane Review of online Cognitive testing highlights:
“There is no consensus on the optimal cognitive assessment, certain tests have greater visibility and traction in research and practice.”
There is a lack of consensus around the optimal tools to use in clinical practice. This means more research into this area is crucial, to ensure that the right tests are selected moving forward in pharmaceutical research as well as for any potential future app or online at home testing.
This week I have been thinking about why Cogstate is getting the focus and who they are competing with. I have done a quick dive into the competitor space. And I will provide a little history around the traditional pen and paper cognitive tests.
Hint: Traditional tests require a trained professional to administer and interpret test results. This is layered with problems including a lack of consistency and variability in how the test is administered. So unless someone invents an uber like service for robotic at home testing administration and oversight, I think this old style of pencil and paper test is going to become obsolete.
Clinical/Paper and Pencil Tests For Background
Mini-mental state exam; MMSE (standardised).
· Developed in 1975
· 10 minutes to administer
· Used in clinical settings
· Paper and pencil
· Scored out of 30
· Provides rate of severity
Mini-Cog test
· Used in secondary care settings – inpatients and outpatient settings
· Detect Alzheimer’s disease and other dementia diseases
· Simple 3 item recall for memory
· Plus clock drawing
Quick side-bar for clarity: A Cochrane review is a compilation and interpretation of all the best research brought together to find overall answers to study questions and find holes that need further research.
So in 2019 a Cochrane review found that there were very significant limitations of the Mini-Cog test, due to the variability in the way the test was being administered, making it difficult to make recommendations about this type of test.
The conclusion can therefore be drawn that this is not the best test for use in inpatient and outpatient settings.
ADAS-COG (Alzheimer’s Disease Assessment Scale)
· Developed in the 1980s
· 30-35 minutes to administer
· 11 sections
· Led by test administrator
· The greater the score out of 70 the greater the dysfunction
· Not useful on patients with severe dementia
Progress to Self-Administered Test: But Still Pencil and Paper
SAGE (Self-Administered Gero-cognitive Exam)
· 15 minutes
· Developed at Ohio State University
· Pen and paper test
· 12 questions, covering areas including memory, problem solving and language
· Free
· 4 test versions
· At-home test but
· Still recommends that results need to be discussed with a qualified doctor
· Claims to accurately detect early signs of Alzheimer’s or Dementia
· Screening tool and not diagnostic test
Progression to Full Computerized Online Tests: Throw Out the Pencils and Save a Forest
Not all online tests are created equal with many of them being very poor screening tools for Alzheimer’s/Dementia. It is important to wade through and find tests with enough validation through multiple years of research and studies.
The FDA has done just this, lucky us and approved the following computerized tests:
1. Automated Neuropsychology Assessment Metric (ANAM)
2. CANTAB (Cambridge)
3. COGNIGRAM (Cogstate)
COGSTATES (CGS) Major Competitors
ANAM: Automated Neuropsychology Assessment Metric
· Developed by US Department of Defence
· Originally designed to measure performance changes in healthy individuals in challenging environments
· 30 years of research
· Run on Desktop/Laptop
· Administered by trained professional
· 20 minutes for core battery of questions
· 45-60 minutes for general battery of questions
· Automatic scoring
· Good for repeat testing
· Limitless alternative forms – control practice effects
· 3 Major areas of focus: processing speed/efficiency, retention/memory, and working memory.
· Detection of cognitive impairments validated
· ANAM doesn’t provide the same info as a comprehensive neuropsychological assessment but it appears sensitive and specific in identifying patients with neurocognitive deficits
What is the catch?
· The ANAM Dementia Battery (DEMBAT) has a flaw: There is no language or delayed memory testing in the battery
· Administered with keyboard mouse – this has limitations and people have found this difficult
CANTAB: Cambridge Neuropsychology Test Automated Battery
Owned by Cambridge Cognition Holdings neuroscience technology company.
Self-promotes as:
“The worlds most validated cognitive assessment software.”
“International Gold Standard.”
Provides computerised testing to over 100 countries and the top 20 pharmaceutical companies and over 800 academic research institutions.
CANTAB’s website describes the test as:
“a pharmacologically sensitive cloud-computing assessment system for use in pharmaceutical clinical trials investigating the cognitive profile and efficacy of treatments for Prodromal Alzheimer’s disease.”
CANTAB stats include:
· Used in >2200 clinical trials
· >15 years of experience
· >1 million patients have assessed digital health apps in clinical trials
· >100,000 sited in peer reviewed papers
· Available in 30 languages
· Web based remote testing
· Secure data encryption and storage
· Touchscreen interface
· Suitable for both health and patient population
CANTAB TEST:
· Tests: working memory, learning, executive function, visual, verbal, episodic memory, attention, information processing, reaction time, social and emotion recognition, decision making and response control
· Administered via computer touchscreen
· Administered via trained technician
· Clinician needed to interpret results
· 35 minutes
· Repeatable standardized testing: 3000 in normative database
· Automatic scoring
· HIPAA compliant data
· Secure real time data via the cloud
· Culturally independent
CANTAB is reported to be the most widely publicized battery with reports on normative data, test-retest reliability and clinical use.
CANTAB can tell the difference between healthy controls, patients with early-stage Alzheimer’s/Dementia and patients with Parkinson’s disease.
Why back Cogstate then?
Well as far as I can tell CANTAB is an excellent competitor.
My guess is that COGNIGRAM pips CANTAB because it is faster to administer and It has been shown to be super easy to use even among older cognitively impaired patients with essentially no computer experience.
COGNIGRAM has recently won major new pharmaceutical giants and they have the most relevant Alzheimer’s drugs being tested. The Aduhelm drug clinical trials using COGNIGRAM has the advantage of currency and relevance. Furthermore, It is more likely to become the-go-to test for future drug competitors as they will want a cognitive test that can directly compare across studies.
COGSTATE’s COGNIGRAM: Forward Thinking
COGNIGRAM is only one of a handful of FDA approved online self- administered computer tests to measure cognition applying for both in-clinic and at-home administration.
As we know the at home administration of any online cognitive test is still being studied and not currently validated. Cogstate appears optimistic that they will be able to successfully validate the COGNIGRAM system for at home / potential app use and crack this market safely.
In 2017 FDA approved COGNIGRAM:
“The COGNIGRAMTM system is a digital cognitive assessment tool with self-administered assessment that can be completed both in-clinic and at-home. It is for prescription use, and is intended to aid healthcare professionals with an objective measurement of cognition for use in individuals aged 6 - 99 years old. The COGNIGRAMTM system can be used to assess cognition on a single occasion or cognitive change over periodic assessments. Performance on the COGNIGRAMTM system is unaffected by language, education, cultural background, or practice.”
“After more than fifteen years of intense efforts in supporting academic research and pharmaceutical clinical trials around the world, Cogstate is excited to enter the U.S. market for cognitive assessment on the front lines of clinical practice,” commented Frank Cheng, President of Cogstate Healthcare. “We look forward to bringing the proven and widely-published COGNIGRAM technology into the healthcare ecosystem to benefit an exponentially larger pool of patients.”
COGNIGRAM:
· 4 tests only 10-15 minutes to do
· Used in 6-99 year olds
· Automated scoring
· Sensitive in home and in clinic
· Unaffected by language, education, cultural background
· No practice effects
· Assess: Processing speed, attention, decision making, working memory, visual learning, visual attention and episodic memory.
· Key board keys to respond
· Good test-retest reliability
· Early discrimination ability
· Very good in older patients with limited computer experience
COGNIGRAMS Other Advantages: As Far As I Can Tell
This one is the kicker not only is it an excellent screening tool but…….It appears to be useful in Intra-individual cognitive decline in healthy and cognitively impaired adults.
Also COGNIGRAM uses the practice effects it has over multiple testing, in a single day to its advantage. Methods can be set up to say administer the 10 minute test, 4 times in the span of 3 hours. This clever test design will reveal the difference between healthy controls and older adults and patients with mild cognitive impairment (MCI). How is this possible? Well healthy adults will show a practice effect over multiple tests on the same day while those adults with MCI will not show this improvement in testing scores as they have impaired learning. Impressive.
Here is a good opportunity to link back to previous straws in the Cogstate Forum:
@Firedup asked a really good question to the Strawman community recently. @Fireup queried whether blood tests and retina scans (I hope to post a straw in the not too distant future about the limitations and possible pitfalls in using retinal scans in Alzheimer’s detection) discussed in Bill’s video will eventually negate the use of COGNIGRAM. Is this company at risk of becoming obsolete?
I agree with @Chagsy – These tests are about screening and identifying patients yes – so in that sense a blood test or retinal photo may also confirm early signs of disease. However COGNIGRAM as @Chagsy says is about identifying function. How well is this person currently managing with life across a basket of different cognitive areas.
We know COGNIGRAM can safely be repeated so we can test to see how a patient is performing in various areas, say every year following the diagnosis. So I feel COGNIGRAM will always be an essential part of Alzheimer’s/Dementia detection and monitoring.
Having the diversified revenue streams of COGNIGRAM pharmacological testing is excellent. While the company works toward the holy grail of an at home cognitive test.
Pharmaceutical study methodologies of new drugs will always compare a baseline cognitive test, to the same test again over time to see if there drug is indeed staving off cognitive decline.
While the three major FDA players differ in normative data and their representation in scientific literature. COGNIGRAMS advantages over its peers appear to be:
· Battery brevity
· User friendliness
· Independent testing free from personnel
· Screening of early cognitive decline plus
· Stability over time make it ideal for dementia monitoring
Validated at-home tests a way off even for COGNIGRAM
Papers such as:
Adler. K., Apple, S., Friedlander, A. Et al.(2019) Computerized cognitive performance assessments in the Brooklyn Cognitive Impairments in Health Disparities Pilot Study. Alzheimer’s & Dementia, Vol 15, 11, p 1420-1426
Have concluded the following:
“The Cognigram was well liked in waiting rooms of primary care settings. Assistance from a trained adult and clinic endorsement were keys to success. How the COGNIGRAM performs in a geographically compact, population-dense global setting, such as Brooklyn with high vascular disease risk and a plethora of health disparities, is being tested.”
Betting on Cogstate: The Future of Computerized At Home Testing We Aren’t Quite There Yet
1. There is currently no consensus about how effective the current FDA approved tests will be if used by a user alone at home. This still needs to be supported by research.
2. Large studies still need to be completed to determine the accuracy of standard pencil and paper tests vs modern computerized tests.
3. Also exactly how to administer and what the optimal follow up testing regime for Alzheimer’s/Dementia patients is has yet to be established.
Future Research
An upcoming Cochrane Review is underway starting in 2020 to do the following:
1. Asses the validity of remote computer testing for cognitive function
2. Assess the validity of remote vs in-person delivery of cognitive testing
It is important to remember that at home screening has not been validated fully and there is concern that tests will produce a high number of false positives. The at-home screening test could cause unnecessary worry and incorrectly identify people who don’t actually have genuine cognitive decline.
Current Studies Underway for COGNIGRAM
According to Clinicaltrial.gov - there are currently longitudinal studies underway looking into the validity of Computerized Cognitive Battery (COGNIGRAM) in the diagnosis of mild cognitive impairment and Alzheimer’s Disease.
Researchers believe there is an advantage of these tests as they are standardized without the interference of an examiner.
The current study is looking to validate COGNIGRAM to determine if changes in scores over 3, 6, 9 and 12 months can predict progression to dementia at 1, 2, and 3 years for patient with mild cognitive impairment. The estimated completion is December 2021.
This study is an important one as positive results are likely to lead to further validation of COGNIGRAM and ultimately a higher Cogstate share price.
Important to Keep In Mind The Benefits of Early Detection Of Cognitive Impairments For Intervention
Early diagnosis has significant benefits. Starting treatments early is beneficial in managing symptoms and delaying progression of the disease.
COGNIGRAM the Ties to Aduhelm and the Controversy
Several previous straws have alluded to the controversy over the FDA approval for Aduhelm. Multiple pharmaceutical companies and bio-techs have been provided with fast-track status during the pandemic due to seriousness and need. Other examples of this include prospective anti-microbial drugs. Some of these drugs have been pushed through faster than usual and multiple hoops have been removed.
So why the controversy?
Aduhelm had 2 phase 3 clinical trials. Only one study met the primary endpoint – evidence of the reduction of patient cognitive decline. The second phase 3 trial failed to meet this primary endpoint.
Tricky! Testing methodology can vary and anyone who has invested in biotechs can fully understand how precarious and variable results can be. All other studies leading to Phase 3 showed that Aduhelm consistently reduced the level of amyloid beta plaques in the brain – the stuff that causes the problems.
Specifically, the Peripheral and Central Nervous System Drugs Advisory Committee in 2020 met and did not agree that one successful phase 3 study was enough to justify FDA approval of Aduhelm. Given the global pandemic and the need – stars aligned and it seems that lots of decisions may have been expedited. Time will tell whether this was wise.
FDA recognised the pressing clinical urgency for treatments as currently over 6 million people in the US have been diagnosed with Alzheimer’s. Given the numbers and mortality rates I can understand that the FDA gave Alduhelm the green light.
Expedited allowances still mean companies have to complete post-approval studies to verify anticipated clinical benefit. These are known as phase 4 confirmatory trials. If anticipated clinical benefit is not shown than the drug may still yet be pulled from the market.
SUMMARY
COGNIGRAM has the advantage of ‘visibility and traction’ in research and clinical practice thanks to its ties to Aduhelm.
It is a valid computerized screening and monitoring tool for detecting cognitive impairment in clinical settings, drug trials and research. Further work still needs to be validated for its benefit as an independent unsupervised at home test.
End of 2021 will hopefully see further validity of this test via the results of a longitudinal computer based study.
CANTAB is certainly a valid competitor in this space but COGNIGRAM seems to have the advantage of speed and ease of administration.
I am interested in everyone else’s thoughts. Are there other significant competitors I may have missed.
Cheers
Nnyck777
Cogstate (CGS) #Musings and #Moats
Thanks Matt and Andrew for the enjoyable macroeconomic and Cogstate stock pitch discussion.
I have just downloaded the Deficit Myth – a further nudge to get this read.
Cogstate is a very interesting company.
I have enjoyed reading the recent Straws from @Mikebrissy and @Rapstar and @Bjbart (is that Matt?).
Picks and shovels analogy definitely works here Andrew for a safer entry bet into the prospective Dementia/Alzheimer’s theme. Let’s hope a smart bet rather than future instruments of our collective investment lobotomy.
I thought I would provide some ‘colour’ as @mikebrisy would say with regard to psychometric testing.
Survey methods and design was actually one of my favourite areas of study during psychology. As riveting as it sounds it was fascinating to understand how psychometric tests, that we commonly use today were developed. I am sure most of us have been exposed to one form of test or another – for work, interviews, medicals and health assessments etc..
Classic tests that many of us may be familiar with include the Weschler Adult Intelligence Scale (WAIS), Beck Depression Inventory (BDI) – commonly used by GPs and the Standardised Mini-mental state exam (SMMSE)/ aka TRUMP test.
I personally really enjoyed learning about lie detection scales and how they worked in certain psychometric tests. Fascinating stuff – you know the good questions! Like have you ever stood on the edge of a cliff and thought about jumping off or have you ever taken anything that wasn’t yours! The questions to distil truth vs socially desirable answers.
The reason for my Straw is that I wanted to whole heartedly agree with @bjbart’s and @Newbie HKs sentiments here around MOAT.
Psychometric test development is a complex and difficult process. Psychologists/ researchers start by asking literally 100’s if not 1000’s of questions around the topic they are targeting using different wording, format, style and sentence structure.
This large test battery is then whittled down and statistically analysed to come up with the list of questions that provide the most validity, reliability and repeatability amongst test takers.
What this means, in a nutshell, is that each question in your psychometric test is rigorously analysed to ensure that it elicits the information that the question is actually designed to test (no confounding influences). The tests need to yield the same response, reliably over multiple occasions to be deemed useful.
As @Bjbart mentioned, once your battery of questions is compiled the test is then used again and again and again on your appropriate cohort. In the case of Cogstate a likely elderly demographic as opposed to poor unsuspecting 1st year psych students.
This process takes time and quite literally years of research. It is unlikely once a test becomes a norm or “standard” that a new test will have the ability to catch up and supplant it due to this head start.
Psychologists like most humans can be creatures of habit. Once familiar with a new tool and comfy with this test they are unlikely to change. Just like doctors/ allied health professionals often become comfy with prescribing certain drug types – as they become well versed in side effects, use case etc...
If, as Matt says the Cognigram Screening tool is further integrated at university level it will become sticky for practitioners and become further entrenched in Dementia/ Alzheimer’s testing trials and research.
Having a consistent clinical cognitive test, a “gold” standard is ideal for all types of research. It is exciting to think of the potential of Cogstate if the Cognigram Screening tool is widely adopted. It certainly seems to be on its way with the Elsai deal.
Having consistent methodology adopted by all drug companies with dementia offerings will make comparison of drug results much easier in future years. Great for the old Cochrane Data Base.
I am super intrigued by this one off to do more research! Thanks for sharing.
Cheers
Nnyck777
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