On an earlier MB thread I was able to work through the numbers with the formula:
z= D/(SD1^^2/n1+ SD2^^2/n2)^^0.5
I have found all the SD values for the two AD phase 3 trials for LMTM.
They are:
Mild Phase 3
n1 =388 SD = 9.698
n2 = 76 SD = 9.674
n3 =309 SD = 9.372
n4 = 79 SD = 8.956
n5 =297 SD = 10.200
Mild Moderate:
n1 =348 SD = 9.661
n2 =257 SD = 12.923
n3 =250 SD = 13.149
n4 =220 SD = 12.07
n5 =213 SD = 12.24
n6 = 37 SD = 8.3
n7 = 37 SD = 8.31
Now What?
We can plug in the values for SD1 and SD2 for the Lucidity trial to get a feel for the numbers expected to be reported.
Note that for the mild phase 3 the SD was ~ 9.5.
z= D/(SD1^^2/n1+ SD2^^2/n2)^^0.5
When we plug SD1=SD2= 9.5; n1=n2=299 with z=2 for ~2.5% upper tail
We have: D= 2*( 2*9.5^^2/299)^^0.5
= 2*(0.777)
= 1.554
1.554 ADAS-cog would be the difference between placebo and LMTM treatment at 2.5% upper tail probability
for ns=299 and standard deviations ~9.5. Yet, we saw a difference closer to 3.1 as reported with the mild phase 3 and the MB phase 2. Doubling the difference by linearly scales the z value up to ~4. A z-value of 4 would be massive.
That would give an upper tail probability of 0.0000317
The standard deviation with the mild moderate phase 3 was higher at ~12.5.
When we plug SD1=SD2= 9.5; n1=n2=299 with z=2 for ~2.5% upper tail
We have: D= 2*( 2*12.5^^2/299)^^0.5
= 2*(1.022)
= 2.045
This is somewhat higher than the result we obtained from SD=9.5. If we linearly scale this up to a difference of 3
we now have a z value of 3 which gives us an upper tail probability of 0.00135.
A not unreasonable expectation would be that the Lucidity phase 3 primary result for ADAS-cog could report out with a p-value of 0.00003 to 0.001; given a treatment difference of ~3. The final n would be somewhat reduced due to patient attrition.
The good thing here is that I can look around and see what other large trials have reported for the SD for placebo with ADAS-COG. This should be essentially a known constant. So, we probably should be able to do better than the range from 9.5 to 12.5 that we used. On page 36 of the FDA Briefing Document for Aducanumab the SD for ADAS-cog 13 for Emerge Arms of sizes 545,542, 546, and 1633 (placebo) the SD were all ~7.0. For engage with similar arm sizes the SDs were ~6.5. These are the baseline SDs (pages 176 and 189). For Emerge at week 78 they report standard errors of ~0.40 with arms sizes of ~290 (page 180). For Engage at week 78 the standard errors are ~0.38 with sample sizes of ~330 (page 192). The sample standard deviations for Aducanumab at week 78 are ~7.0. Note here they are using ADAS-cog 13 and not ADAS-cog 11 (these two tests might have somewhat different SDs).
AD cured? taurx reports positive Lucidity results !!!!!!!!!!
Re: AD cured? TauRx reports positive Lucidity results !!!!!!!!!!
Last edited by J11 on Sat Jun 04, 2022 9:50 am, edited 3 times in total.
Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!
Hi J11,
When you have time and it is appropriate, would you summarize what you think someone could to execute a DIY experiment to mimic the results in the homotaurine and methylene blue space? Including product sources, dosing and timing.
Thanks so much for your efforts to keep us abreast of this information!!
Tincup
E3,E4
E3,E4
Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!
Tincup, thank you for replying!
This is a seismic event in the history of Alzheimer dementia treatment!
From my number crunching above, my feeling is that taurx has hit a lowish p-value perhaps with a treatment difference from placebo of ~3 ADAS-cog points. This could have a monumental effect on clinical AD management over the shortish term. The idea that I have mentioned before of just shutting off the dementia conveyor belt appears to now be possible across a wide range of dementia pathology from pre-symptomatic, MCI, mild and into moderate and possibly beyond. This is very startling! We have been waiting for this to be clarified for 15 years and now it has!
This is clearly a turning point for modern human civilization. Life has become to an extent unrealized by many, a life whose dominate purpose is to care for those with dementing illness. With an effective treatment, other life purposes
could move to center stage.
This truly is Alzheimer Liberation Day (part two)!
We might have now reached the inflection point that I have suggested for some time. Alzheimer's dementia soaks up ~ $1 billion of government resources per day and is growing exponentially. LMTM will allow us to shut off the tap across the disease spectrum. Such power could rapidly give us the power to liberate that $300 billion in resources for other priorities. The sooner treatment rollouts -- the sooner the dementia dividend cheque can be cashed. For the dementia families, the payback would have even greater personal meaning-- it would mean that loved ones would no longer descend into irreversible decline.
This is a monumental day for Alzheimer's; a day preceded by centuries of anguish by the dementia community. It is so reassuring to me knowing that I will have access to a front-line anti-amyloid treatment and now also a second line anti-tau treatment. With LMTM I think it would not be unreasonable to think of it also as a front-line that could also be given before disease onset.
My intuition is telling me that taurx could go with a low-ball pricing strategy. Methylene blue is a widely available chemical online-- it is essentially universally present. I have already loaded up with it. However, given a choice I would still prefer to buy it above board. It does help when everyone pools their money together and encourages the ongoing research that will be needed. By low-balling it, a nearly unlimited market opens up. There would be no reason to try to outwait the patent. Population scale dosing could ensue-- a statin for the brain. This could become a win all around.
This is a seismic event in the history of Alzheimer dementia treatment!
From my number crunching above, my feeling is that taurx has hit a lowish p-value perhaps with a treatment difference from placebo of ~3 ADAS-cog points. This could have a monumental effect on clinical AD management over the shortish term. The idea that I have mentioned before of just shutting off the dementia conveyor belt appears to now be possible across a wide range of dementia pathology from pre-symptomatic, MCI, mild and into moderate and possibly beyond. This is very startling! We have been waiting for this to be clarified for 15 years and now it has!
This is clearly a turning point for modern human civilization. Life has become to an extent unrealized by many, a life whose dominate purpose is to care for those with dementing illness. With an effective treatment, other life purposes
could move to center stage.
This truly is Alzheimer Liberation Day (part two)!
We might have now reached the inflection point that I have suggested for some time. Alzheimer's dementia soaks up ~ $1 billion of government resources per day and is growing exponentially. LMTM will allow us to shut off the tap across the disease spectrum. Such power could rapidly give us the power to liberate that $300 billion in resources for other priorities. The sooner treatment rollouts -- the sooner the dementia dividend cheque can be cashed. For the dementia families, the payback would have even greater personal meaning-- it would mean that loved ones would no longer descend into irreversible decline.
This is a monumental day for Alzheimer's; a day preceded by centuries of anguish by the dementia community. It is so reassuring to me knowing that I will have access to a front-line anti-amyloid treatment and now also a second line anti-tau treatment. With LMTM I think it would not be unreasonable to think of it also as a front-line that could also be given before disease onset.
My intuition is telling me that taurx could go with a low-ball pricing strategy. Methylene blue is a widely available chemical online-- it is essentially universally present. I have already loaded up with it. However, given a choice I would still prefer to buy it above board. It does help when everyone pools their money together and encourages the ongoing research that will be needed. By low-balling it, a nearly unlimited market opens up. There would be no reason to try to outwait the patent. Population scale dosing could ensue-- a statin for the brain. This could become a win all around.
Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!
The numbers for LMTM are massive.
The top figure shows the results for the phase 2 trial with methylene (Blue MB) a chemical highly similar to LMTM.
As seen ADAS-cog declined by ~4 points on a true placebo without AD co-medication after one year which is in the range of expectation of decline ADAS-cog 11 of 4-6 points per year. The MB treated patients at 138 mg per day declined by ~ 1-1.5 points.
Next figure is the Mild Moderate AD phase 3. At the 1 year point those on 75 mg (n=37) 125 mg (n=37) and 4 mg (n=52) monotherapy improved by ~1-2 points. Those on add-on treatment declined by ~4.3 points at 1 year.
Bottom figure is for the Mild AD phase 3. The article did not do the comparison between all those on add-on and all those on monotherapy; this comparison is done in the right hand figure labeled comparison D. The weighted average decline on add-on at week 76 is 7.18 points with n=606 and on monotherapy 3.03 points with n=155.
To calculate the standard error I used this formula:
To calculate the combined standard errors formula
e3^^2 = (1/(n*(n-1)))*(n1(n1-1)*e1^^2 + n2(n2-1)*e1^^2 + n1n2/n (m1-m2)^^2)
n = n1 + n2
SE total Add-on = 0.39722161 --> 0.39722161 *606^^0.5 = 9.778 SD1
SE total mono - 0.74581942 --> 0.74581942 *155^^0.5 = 9.285 SD2
I then used this online calculator to find the T-score.
T-score 4.91
https://www.infrrr.com/means/difference ... calculator
To double check this approach use the numbers from Comparison A
3.14 (5.32 --> 0.97) 4.35 = 2*1.96 SE = 3.92 SE
3.92 SE = 4.35
1 SE = 1.1096939
3.14 / 1.1096939 = 2.829609 = Z
P(x<-Z or x>Z) = 0.0046605
https://www.calculator.net/z-score-calc ... #converter
To put all the number into the hat, we can use the 37 + 37 + 52 monotherapy patients from the Mild Moderate P3;
and also the 155 monotherapy patients in the Mild P3; and also the 220+213+296 add-on patients from the mild moderate p3 and also the 606 addons from the Mild p3. This is a total of 308 monos and 1335 addons. The monos had ~0 ADAS-cog 11 decline over 1 year while the addons had ~4.3; using 9.5 SD the online calculator gives us
7.2 Z score which is not even provided in the normal score tables-- it doesn't go that high.
Of course the add-ons are thought to derive some benefit from receiving LMTM, so even 7 isn't the correct number.
True number for the 2 phase 3 combined is ~8.3 z score!!
As a guess for the awaited results of the Lucidity trial, we could use n1=220, n2=220, SD1=9.5; SD2=9.5 , m1=0, m2=5.
Published AD research tells us that after 1 year ADAS-cog declines 4-6 points; we'll use 5. this gives us a T-score of 5.5. That is a truly massive number. It would be extremely clinically meaningful as it would mean that clinical progression had been stopped for one year. The 8 mg per day used in earlier research is thought to be somewhat underdosing, so it can be expected that the 16 mg per day dose used in Lucidity will be somewhat more effective.
During the trial changes were made to include moderate patients, so this might influence the reported top line as well.
The top figure shows the results for the phase 2 trial with methylene (Blue MB) a chemical highly similar to LMTM.
As seen ADAS-cog declined by ~4 points on a true placebo without AD co-medication after one year which is in the range of expectation of decline ADAS-cog 11 of 4-6 points per year. The MB treated patients at 138 mg per day declined by ~ 1-1.5 points.
Next figure is the Mild Moderate AD phase 3. At the 1 year point those on 75 mg (n=37) 125 mg (n=37) and 4 mg (n=52) monotherapy improved by ~1-2 points. Those on add-on treatment declined by ~4.3 points at 1 year.
Bottom figure is for the Mild AD phase 3. The article did not do the comparison between all those on add-on and all those on monotherapy; this comparison is done in the right hand figure labeled comparison D. The weighted average decline on add-on at week 76 is 7.18 points with n=606 and on monotherapy 3.03 points with n=155.
To calculate the standard error I used this formula:
To calculate the combined standard errors formula
e3^^2 = (1/(n*(n-1)))*(n1(n1-1)*e1^^2 + n2(n2-1)*e1^^2 + n1n2/n (m1-m2)^^2)
n = n1 + n2
SE total Add-on = 0.39722161 --> 0.39722161 *606^^0.5 = 9.778 SD1
SE total mono - 0.74581942 --> 0.74581942 *155^^0.5 = 9.285 SD2
I then used this online calculator to find the T-score.
T-score 4.91
https://www.infrrr.com/means/difference ... calculator
To double check this approach use the numbers from Comparison A
3.14 (5.32 --> 0.97) 4.35 = 2*1.96 SE = 3.92 SE
3.92 SE = 4.35
1 SE = 1.1096939
3.14 / 1.1096939 = 2.829609 = Z
P(x<-Z or x>Z) = 0.0046605
https://www.calculator.net/z-score-calc ... #converter
To put all the number into the hat, we can use the 37 + 37 + 52 monotherapy patients from the Mild Moderate P3;
and also the 155 monotherapy patients in the Mild P3; and also the 220+213+296 add-on patients from the mild moderate p3 and also the 606 addons from the Mild p3. This is a total of 308 monos and 1335 addons. The monos had ~0 ADAS-cog 11 decline over 1 year while the addons had ~4.3; using 9.5 SD the online calculator gives us
7.2 Z score which is not even provided in the normal score tables-- it doesn't go that high.
Of course the add-ons are thought to derive some benefit from receiving LMTM, so even 7 isn't the correct number.
True number for the 2 phase 3 combined is ~8.3 z score!!
As a guess for the awaited results of the Lucidity trial, we could use n1=220, n2=220, SD1=9.5; SD2=9.5 , m1=0, m2=5.
Published AD research tells us that after 1 year ADAS-cog declines 4-6 points; we'll use 5. this gives us a T-score of 5.5. That is a truly massive number. It would be extremely clinically meaningful as it would mean that clinical progression had been stopped for one year. The 8 mg per day used in earlier research is thought to be somewhat underdosing, so it can be expected that the 16 mg per day dose used in Lucidity will be somewhat more effective.
During the trial changes were made to include moderate patients, so this might influence the reported top line as well.
Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!
The topline numbers which might be reported next week reasonably could be very extreme.
Everyone prepare to celebrate!
Everyone prepare to celebrate!
Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!
Hmm, online sources are questioning whether the taurx's press release represent positive top-line results.
"LUCIDITY data suggest that participants receiving hydromethylthionine mesylate (HMTM) decline at a rate substantially less than is typical in Alzheimer’s based on published research ... This was seen for both cognitive and functional endpoints across a broad range of severity from mild cognitive impairment (MCI) to moderate Alzheimer’s. Importantly, the safety profile is favourable and consistent with previous studies. ... Prior to the release of the LUCIDITY interim data, the UK Medicines & Healthcare products Regulatory Agency (MHRA) granted the company an Innovation Passport on 18th May 2022. The Innovation Passport is the first stage of the Innovative Licensing and Access Pathway (ILAP), which is intended to accelerate development and approval times, facilitating access to new products and indications. ... The ILAP designation represents a clear signal of regulatory support for a prospective treatment breakthrough in Alzheimer’s"
I am not perceiving any equivocation in their statements. Assuming words have meaning, the press release is qualitatively expressing the idea that LMTM hit its co-primaries on the ADAS-cog 11 and ADCS-ALD (if I am understanding it properly).
Also they are referring to a possible accelerated launch by late 2023. If they hit the numbers suggested above -- this could wait a year or two???
"LUCIDITY data suggest that participants receiving hydromethylthionine mesylate (HMTM) decline at a rate substantially less than is typical in Alzheimer’s based on published research ... This was seen for both cognitive and functional endpoints across a broad range of severity from mild cognitive impairment (MCI) to moderate Alzheimer’s. Importantly, the safety profile is favourable and consistent with previous studies. ... Prior to the release of the LUCIDITY interim data, the UK Medicines & Healthcare products Regulatory Agency (MHRA) granted the company an Innovation Passport on 18th May 2022. The Innovation Passport is the first stage of the Innovative Licensing and Access Pathway (ILAP), which is intended to accelerate development and approval times, facilitating access to new products and indications. ... The ILAP designation represents a clear signal of regulatory support for a prospective treatment breakthrough in Alzheimer’s"
I am not perceiving any equivocation in their statements. Assuming words have meaning, the press release is qualitatively expressing the idea that LMTM hit its co-primaries on the ADAS-cog 11 and ADCS-ALD (if I am understanding it properly).
Also they are referring to a possible accelerated launch by late 2023. If they hit the numbers suggested above -- this could wait a year or two???
Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!
Why hasn't the share price of Genting moved????? Genting jumped 10 cents on the initial LMTM news and has then largely stabilized, even while it owns 20% of taurx. It is very convenient to have a stock market proxy to tells us what money thinks of the results. Apparently not that much.
How is an AD treatment that possibly stabilizes dementia progression for at least ~ 1 year not worth more than 10 cents? Even going with a low ball pricing strategy it will still generate an enormous amount of revenue. There is some online chatter that the intention is to price LMTM at $56,000 per year -- hopefully that is a misreport; we saw how well that went. Opening this up to essentially population scale dosing (and population scale pricing) would seem to be the best strategy. A range of problems could emerge if the plan is to extract maximal wealth from AD patients.
How is an AD treatment that possibly stabilizes dementia progression for at least ~ 1 year not worth more than 10 cents? Even going with a low ball pricing strategy it will still generate an enormous amount of revenue. There is some online chatter that the intention is to price LMTM at $56,000 per year -- hopefully that is a misreport; we saw how well that went. Opening this up to essentially population scale dosing (and population scale pricing) would seem to be the best strategy. A range of problems could emerge if the plan is to extract maximal wealth from AD patients.
Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!
Ok, here's the annotated version of the taurx press release. What did the press release really mean? Especially for those who are not English as a First Language speakers it is worthwhile to highlight the connotations of the specific words that were used to attain a more sensitive understanding of what the press release is communicating.
The pink highlighted words represent weasel words. These words equivocate on exact meaning. The green words are strong words that express statements forcefully. The blue words have initially somewhat unclear meaning, though can be further clarified.
The headline first sentence is clear enough: HMTM is intended to be moved to regulatory submission. Regulatory submission would only be reasonably contemplated if Lucidity achieved a statistically significant ( at least 5%, realistically quite a bit more than just hitting the line) result on both co-primaries -- ADAS-cog 11 and ADCS-ADL.
"initial data" was initially somewhat confusing: what do they mean by "initial data"? The "initial data" is the primary readout that happened one year after the trial enrolled. This is the data from Lucidity that they have just unblinded. The trial fully enrolled in January 2021 and 52 weeks of treatment brought us to January 2022. By January of 2023, the open label extension data will have been gathered with all patients being treated for a year of on label treatment after either a year of placebo or active treatment. As was seen in previous research the cognitive benefit can increase quite a bit with another year of treatment. It will obviously be very interesting to see how those on initially placebo respond to treatment against their own documented decline.
Suggest is a weak word used to describe the benefit received. It is then somewhat contradicted in the same sentence with substantially less (decline). When this same statement is restated on the second go through, suggest is replaced by indicates which is a stronger phrasing. "published research" is a weak and likely misleading phrasing. Lucidity was a randomized placebo controlled phase 3 clinical trial. Why would "published research" (historical controls?) even be referenced? Statistical significance is established empirically by comparing treated versus control patients. All of the confusions related to dosing and add-on interference hopefully is now all behind us. Isn't it?
The press release then continues by noting that benefit was seen across cognitive (i.e., ADAS-cog 11) and functional (i.e., ADCS-ADL) endpoints.
Of interest when doing this word by word close reading, the statement that the benefit was found broad range of severity from mild cognitive impairment (MCI) to moderate Alzheimer’s really leapt off the page for me. What this would seem to imply is that they achieved statistically significant results for both sub-groups. That would be remarkable. If you have 598 total patients; divide them into 299 on treatment and 299 on placebo- and then possibly subgroup patients into perhaps 150 mild and 150 moderate patients for both treatment and placebo -- and then ~1/3 drop out of the trial. You are only left with 100 in each arm. The t-score of 2.3 resulting from a 3 point ADAS-cog 11 difference (3 points would be a weakish result for Lucidity) with 100 patients in each arm still leaves a p-value of 1.3%. Assuming that this line of thinking is correct (namely, that LMTM achieved statistical significance for mild and moderate patients separately), then the topline readout would be forced to be a massive success. Combining the mild and moderate arms with 100 patients each with a 3 point difference then gives a t-score of 3.1 and a p-value of 0.09%.
"Tau-targeting Alzheimer’s treatment, HMTM, moving toward regulatory submission based on initial data from TauRx’s LUCIDITY trial
• LUCIDITY data suggest that participants receiving hydromethylthionine mesylate (HMTM) decline at a rate substantially less than is typical in Alzheimer’s based on published research
• Safety profile is favourable and consistent with previous HMTM studies
• TauRx will now pursue regulatory submission and coverage for HMTM
Aberdeen, UK and Singapore, May 31, 2022 – TauRx Pharmaceuticals Ltd, the global leader in tau-based research in Alzheimer’s, today announced unblinding of initial data from completion of the randomised portion of their pivotal Phase 3 clinical trial, LUCIDITY (NCT03446001).
TauRx’s lead investigative oral drug, HMTM, has been tested in 598 people with Alzheimer’s. Following our 12 month blinded phase of the study, participants have moved forward to an additional one year open label phase.
Professor Claude Wischik, Executive Chairman and Co-Founder of TauRx, commented: “The output indicates that participants receiving HMTM decline at a rate substantially less than is typical in Alzheimer’s based on published research. This was seen for both cognitive and functional endpoints across a broad range of severity from mild cognitive impairment (MCI) to moderate Alzheimer’s. Importantly, the safety profile is favourable and consistent with previous studies.
“Our data analysis is ongoing and will be reported at a later date. We look forward to providing an update on our progress on 9th June 2022 at the 35th Global Conference of Alzheimer's Disease International.
“Our expert advisors including EVERSANA are confident in our moving toward regulatory submission and gaining coverage for HMTM.
“Today with limited treatments for Alzheimer’s, the standard of care does not impact the underlying causes of symptom progression. HMTM aims to significantly slow disease progression, providing longer term benefits compared to medications brought to market almost twenty years ago.”
Prior to the release of the LUCIDITY interim data, the UK Medicines & Healthcare products Regulatory Agency (MHRA) granted the company an Innovation Passport on 18th May 2022. The Innovation Passport is the first stage of the Innovative Licensing and Access Pathway (ILAP), which is intended to accelerate development and approval times, facilitating access to new products and indications.
Professor Wischik explains, “The ILAP designation represents a clear signal of regulatory support for a prospective treatment breakthrough in Alzheimer’s, which remains one of the world’s greatest unmet medical needs. Dementia is a leading cause of death around the world, and the Innovation Passport, as the first stage of the ILAP scheme, enables access to the collaborative approach of regulators and associated health technology assessment bodies to both drug licensing and access throughout the UK.
Page 2 of 3
www.taurx.com
“We recognise and publicly thank the incredible commitment from participants and partners involved in LUCIDITY. Our scientific focus on the role of tau pathology in neurodegenerative disease with support from our shareholders and team has enabled us to reach this important milestone.”
With the vision to change the diagnostic and dementia care landscape, the joint venture between TauRx and Genting Berhad, GT Diagnostics, continues to move forward with developing new diagnostic tau biomarker and psychometric tools. These tools will aid in earlier and more accurate identification of people with Alzheimer’s and are designed to assist in management through the progression of symptoms.
With an estimated 50 million people worldwide with Alzheimer’s, their families, healthcare professionals and society, TauRx share their aim in finding a safe and effective management."
The pink highlighted words represent weasel words. These words equivocate on exact meaning. The green words are strong words that express statements forcefully. The blue words have initially somewhat unclear meaning, though can be further clarified.
The headline first sentence is clear enough: HMTM is intended to be moved to regulatory submission. Regulatory submission would only be reasonably contemplated if Lucidity achieved a statistically significant ( at least 5%, realistically quite a bit more than just hitting the line) result on both co-primaries -- ADAS-cog 11 and ADCS-ADL.
"initial data" was initially somewhat confusing: what do they mean by "initial data"? The "initial data" is the primary readout that happened one year after the trial enrolled. This is the data from Lucidity that they have just unblinded. The trial fully enrolled in January 2021 and 52 weeks of treatment brought us to January 2022. By January of 2023, the open label extension data will have been gathered with all patients being treated for a year of on label treatment after either a year of placebo or active treatment. As was seen in previous research the cognitive benefit can increase quite a bit with another year of treatment. It will obviously be very interesting to see how those on initially placebo respond to treatment against their own documented decline.
Suggest is a weak word used to describe the benefit received. It is then somewhat contradicted in the same sentence with substantially less (decline). When this same statement is restated on the second go through, suggest is replaced by indicates which is a stronger phrasing. "published research" is a weak and likely misleading phrasing. Lucidity was a randomized placebo controlled phase 3 clinical trial. Why would "published research" (historical controls?) even be referenced? Statistical significance is established empirically by comparing treated versus control patients. All of the confusions related to dosing and add-on interference hopefully is now all behind us. Isn't it?
The press release then continues by noting that benefit was seen across cognitive (i.e., ADAS-cog 11) and functional (i.e., ADCS-ADL) endpoints.
Of interest when doing this word by word close reading, the statement that the benefit was found broad range of severity from mild cognitive impairment (MCI) to moderate Alzheimer’s really leapt off the page for me. What this would seem to imply is that they achieved statistically significant results for both sub-groups. That would be remarkable. If you have 598 total patients; divide them into 299 on treatment and 299 on placebo- and then possibly subgroup patients into perhaps 150 mild and 150 moderate patients for both treatment and placebo -- and then ~1/3 drop out of the trial. You are only left with 100 in each arm. The t-score of 2.3 resulting from a 3 point ADAS-cog 11 difference (3 points would be a weakish result for Lucidity) with 100 patients in each arm still leaves a p-value of 1.3%. Assuming that this line of thinking is correct (namely, that LMTM achieved statistical significance for mild and moderate patients separately), then the topline readout would be forced to be a massive success. Combining the mild and moderate arms with 100 patients each with a 3 point difference then gives a t-score of 3.1 and a p-value of 0.09%.
"Tau-targeting Alzheimer’s treatment, HMTM, moving toward regulatory submission based on initial data from TauRx’s LUCIDITY trial
• LUCIDITY data suggest that participants receiving hydromethylthionine mesylate (HMTM) decline at a rate substantially less than is typical in Alzheimer’s based on published research
• Safety profile is favourable and consistent with previous HMTM studies
• TauRx will now pursue regulatory submission and coverage for HMTM
Aberdeen, UK and Singapore, May 31, 2022 – TauRx Pharmaceuticals Ltd, the global leader in tau-based research in Alzheimer’s, today announced unblinding of initial data from completion of the randomised portion of their pivotal Phase 3 clinical trial, LUCIDITY (NCT03446001).
TauRx’s lead investigative oral drug, HMTM, has been tested in 598 people with Alzheimer’s. Following our 12 month blinded phase of the study, participants have moved forward to an additional one year open label phase.
Professor Claude Wischik, Executive Chairman and Co-Founder of TauRx, commented: “The output indicates that participants receiving HMTM decline at a rate substantially less than is typical in Alzheimer’s based on published research. This was seen for both cognitive and functional endpoints across a broad range of severity from mild cognitive impairment (MCI) to moderate Alzheimer’s. Importantly, the safety profile is favourable and consistent with previous studies.
“Our data analysis is ongoing and will be reported at a later date. We look forward to providing an update on our progress on 9th June 2022 at the 35th Global Conference of Alzheimer's Disease International.
“Our expert advisors including EVERSANA are confident in our moving toward regulatory submission and gaining coverage for HMTM.
“Today with limited treatments for Alzheimer’s, the standard of care does not impact the underlying causes of symptom progression. HMTM aims to significantly slow disease progression, providing longer term benefits compared to medications brought to market almost twenty years ago.”
Prior to the release of the LUCIDITY interim data, the UK Medicines & Healthcare products Regulatory Agency (MHRA) granted the company an Innovation Passport on 18th May 2022. The Innovation Passport is the first stage of the Innovative Licensing and Access Pathway (ILAP), which is intended to accelerate development and approval times, facilitating access to new products and indications.
Professor Wischik explains, “The ILAP designation represents a clear signal of regulatory support for a prospective treatment breakthrough in Alzheimer’s, which remains one of the world’s greatest unmet medical needs. Dementia is a leading cause of death around the world, and the Innovation Passport, as the first stage of the ILAP scheme, enables access to the collaborative approach of regulators and associated health technology assessment bodies to both drug licensing and access throughout the UK.
Page 2 of 3
www.taurx.com
“We recognise and publicly thank the incredible commitment from participants and partners involved in LUCIDITY. Our scientific focus on the role of tau pathology in neurodegenerative disease with support from our shareholders and team has enabled us to reach this important milestone.”
With the vision to change the diagnostic and dementia care landscape, the joint venture between TauRx and Genting Berhad, GT Diagnostics, continues to move forward with developing new diagnostic tau biomarker and psychometric tools. These tools will aid in earlier and more accurate identification of people with Alzheimer’s and are designed to assist in management through the progression of symptoms.
With an estimated 50 million people worldwide with Alzheimer’s, their families, healthcare professionals and society, TauRx share their aim in finding a safe and effective management."
Last edited by J11 on Mon Jun 06, 2022 12:23 pm, edited 8 times in total.
Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!
At a minimum taurx should report the topline result for the Lucidity phase 3 trial at the 35th Global Conference of Alzheimer’s Disease starting on June 9th, 2022 in London. The results locked as of January 22, 2022 (?), so for a 598 patient trial it does not seem unreasonable that they could provide at least the topline number next week.
