AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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34 hours 54 minutes to go!

The excitement builds!
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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24 hours to go!
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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taurx also released its recent Lucidity press release in Chinese.

The problem is that at some point in the future the primary reference point for establishing legal meaning could shift to Chinese; we would then have not much of an idea about how the Chinese language connotations might translate into English conotations. At this time the assumption would seem to be that the English language version should be considered to fix legal meaning.

The text below is completely hieroglyphic to me.

LUCIDITY 试验数据表明,接受甲磺酸氢甲硫堇(HMTM )治疗的受试者其认知功能下降的速度,大幅低于根据已发表的研究结果显示的阿尔茨海默症的典型下降速度
• 安全性特征良好,与之前的HMTM 相关研究结果一致
• TauRx 接下来将推进HMTM的监管申报和适应症覆盖范围的申请提交

英国阿伯丁和新加坡,2022 年5 月31 日-TauRx Pharmaceuticals Ltd (卓睿药业) ,这家基于tau蛋白的阿尔茨海默症研究的全球领先企业,今天宣布揭盲其关键性III期临床试验LUCIDITY (NCT03446001)随机部分完成所获得的初始数据。
TauRx 的主要研究口服药物HMTM 已经在598名阿尔茨海默症患者中进行了测试。在我们为期12 个月的设盲期研究后,受试者已继续进入了额外一年期的开放标签 ( open label ) 研究阶段。
TauRx 执行董事长兼联合创始人Claude Wischik 教授评论道:“这一阶段产出的数据
表明接受HMTM治疗的受试者的认知功能下降率,大幅低于根据已发表的研究结果显示的阿尔茨海默症的典型下降速度。这在认知和功能终点都能看到,且从轻度认知障碍(MCI )到中度阿尔茨海默症广泛的疾病严重程度范围都能体现。重要的是其安全性特征良好,与既往相关研究结果一致。”
“我们的数据分析正在进行中,将在晚些时候报告。我们期待于2022 年6 月9 日在第35 届全球阿尔茨海默症国际会议(ADI) 会议上呈现我们的最新进展。”
“我们的专家顾问(包括EVERSANA )对我们即将向监管局提交申请并为HMTM 获得相应的适应症覆盖充满信心。”
“今天,由于阿尔茨海默症的治疗手段有限,标准疗法还无法影响症状进展的根本原因。HMTM 旨在显著减缓疾病进展,与近20 年前上市的药物相比,提供更长期的获益。”
在发布LUCIDITY 期中数据之前,英国药品和健康产品管理局(MHRA)于2022 年5 月18 日授予该公司创新凭证(Innovation Passport) 。创新凭证是创新许可和准入路径(ILAP )的第一阶段,旨在加快开发和审批时间,促进获取新产品和新适应症。
Wischik 教授解释说:“ILAP 的资格认定代表了监管局支持阿尔茨海默症前瞻性治疗突破的明确信号,而阿尔茨海默症仍然是全球最大的未满足医疗需求之一。痴呆症是世界各地一大主要死亡原因,作为ILAP 计划的第一阶段,创新凭证使监管局和相关医疗卫生技术评估机构能够通过协作在英国全境获得药品许可和准入。




Hmm, online translation gives a good reverse translation.



Press release
Based on initial data from TauRx's LUCIDITY trial, HMTM targeting tau pathology in Alzheimer's disease is gradually becoming eligible for regulatory submissions
• Data from the LUCIDITY trial showed that subjects treated with hydromethionine mesylate (HMTM) experienced a rate of cognitive decline that was substantially slower than the rate of decline typical of Alzheimer's disease based on published findings
• Good safety profile, consistent with previous HMTM-related studies
• TauRx will next advance HMTM's regulatory filing and application submission for indication coverage

Aberdeen, United Kingdom and Singapore, 31 May 2022 - TauRx Pharmaceuticals Ltd (ZuoRui Pharmaceuticals), the global leader in tau-based Alzheimer's disease research, today announced the unblinding of its pivotal Phase III Initial data obtained from the randomized portion of the clinical trial LUCIDITY (NCT03446001).
TauRx's lead investigational oral drug, HMTM, has been tested in 598 Alzheimer's patients. After our 12-month blinded study, subjects have moved on to an additional one-year open label period research stage.

Professor Claude Wischik, Executive Chairman and Co-Founder of TauRx, commented: “The data produced at this stage showed that the rate of cognitive decline in subjects treated with HMTM was substantially lower than the rate of decline typical of Alzheimer's disease based on published research results. This was seen across both cognitive and functional endpoints and across a broad spectrum of disease severity from mild cognitive impairment (MCI) to moderate Alzheimer's. Importantly, its safety profile is good, consistent with the results of previous relevant studies. "

"Our data analysis is in progress and will be reported at a later date. We look forward to presenting at the 35th Global Alzheimer's International Conference (ADI) on June 9, 2022 Present our latest progress at the conference. "

"Our expert advisors, including EVERSANA, are confident that we are about to submit an application to the regulatory authority and obtain appropriate indication coverage for HMTM."

“Today, with limited treatment options for Alzheimer’s disease, standard therapies have not been able to affect the underlying cause of symptom progression. HMTM is designed to significantly slow disease progression, offering longer-term benefits than drugs marketed nearly 20 years ago. ."
The UK's Medicines and Health Products Regulatory Agency (MHRA) awarded the company an Innovation Passport on 18 May 2022, ahead of the release of LUCIDITY's interim data. The Innovation Voucher is the first stage of the Innovation Licensing and Access Pathway (ILAP), designed to accelerate development and approval times and facilitate access to new products and indications.

Wischik The professor explained: "The ILAP designation represents a clear signal that the regulatory authority supports a breakthrough in the prospective treatment of Alzheimer's disease, which remains one of the largest unmet medical needs worldwide. Dementia is a major global concern. A leading cause of death, as the first phase of the ILAP scheme, the Innovation Voucher enables regulatory authorities and relevant health technology assessment bodies to collaborate in obtaining medicines licensing and access across the UK.

"We highly recognize and publicly acknowledge the extraordinary input of the subjects and partners involved in the LUCIDITY trial. With the support of our shareholders and team, our scientific focus on the role of tau pathology in neurodegenerative disease allows us to Achieving this important milestone."

GT Diagnostics, a joint venture between TauRx and Genting Berhad, continues to forge ahead to develop new biomarkers and psychometric tools for diagnosing tau with a vision to transform the diagnostics and dementia care landscape. These tools will help identify Alzheimer's patients earlier and more accurately, and are designed to aid throughout the course of care as symptoms progress.

The estimated fifty million Alzheimer's patients worldwide, their families, healthcare professionals, society at large, and TauRx share a common goal of finding a safe and effective medical treatment.

Finish
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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https://www.timeanddate.com/worldclock/ ... 36,179,122

Yeah, Launch! Launch a new post-Alzheimer dementia life!

https://www.timeanddate.com/countdown/l ... font=serif

Kuala Lumpur is included with the clocks because GENTING BHD trades on the Kuala Lumpur stock Exchange (KLSE)
in Malaysian ringgits with the stock designator GENTING (3182). Genting BHD owns 20% of taurx and has the most exposure of any listed company. KL market is set to open at 9 AM Kuala Lumpur time in ~ 3 hours. The Kuala Lumpur time zone is easy to determine when given NY time because the two time zones are antipodal.
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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Kuala Lumpur stock exchange has just opened.
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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This is super exciting!

We bought supplies for a party for 12:45 PM London time. But we've finished most it already!
Goodbye tasty Camembert.


Obviously this would be a good time to try to reach for one of my more emotional interpretations of the situation.
When I have drifted into that mindspace, I have been thinking that the announcement at 12:45 PM London time could be embraced as a moment of revolutionary regulatory democracy. This will be of monumental importance to the 55 million people currently coping with clinical Alzheimer dementia. The numbers are just so extreme.

The rough number outline is that we are expecting ~~ 4 ADAS-cog benefit {CI 3-5}. That would be a massive amount of slowing ~80-90% varying with subgroups. What if there is a sense that we don't wan to wait until the end of 2023 for the official regulatory decision. What if We the people want treatment access now? A moment of radical democracy? Is it plausible to simply override the legal norm through the sheer force of the dementia community and their adjacent and aligned allies. It could be not much more than waving through some nutritional supplement packages from Malaysia. If this were to happen it would probably be in the best interests of patients that it were done through the front door with medical supervision. Agree to disagree if necessary but accept the Right to Try doctrine as a fundamental human right option available to patients in this instance.
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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Make this an early night every one!
There could be a people's revolution tomorrow!

I am wondering how many people might jump in their cars tomorrow morning get on the freeway; get stuck in a traffic jam on the freeway; turn on the news and hear the Lucidity end of Alzheimer's announcement and just say to themselves: No, no office for me today.

This will be so large.

I am just worrying that I might sleep in. Set the alarm; alarm rings; find alarm; turn off alarm go back to sleep-- miss the biggest morning in the history of the universe since the Big Bang. No stress there.

One additional comment is the taurx's Chinese language press release for the initial Lucidity findings when translated to English with an online translator is almost the same as the English language version. "indicates" --> "shows" etc. which is very good. I wonder whether there has been some sort of organized effort to anchor meanings of words between languages so that online translation can be of high quality. Words such as suggest, indicate have certain connotations in English which would be helpful to have in corresponding words in other languages. It might require some behind the scenes jiggling to get it quite right.
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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9 minute Countdown!

Not 100%, yet the celebration could now start soon.
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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So, they didn't release any substantive updates on the topline results for Lucidity? There is no intention to do so at the ADI conference?

I suppose that should have been somewhat predicted, though Lucidity was reported to have been fully enrolled by at least January 11th, 2021. More than 5 months are required to number crunch the basic headline number with what the conference seminar disclosed was only 470 patient completers of Lucidity at year 1?

One can now well imagine the next plausible announcement date for the actual data release. For those so called skilled in the art, this should not be an overly strenuous mental challenge.

With the COVID pandemic it became self-apparent that delaying regulatory approval of therapeutics and vaccines for even days had overwhelming health and economic consequences. These consequences are also present with the Alzheimer dementia pandemic though are made less visible to the community. There has been somewhat of a return to life as it was before COVID, one wonders how much longer we will need to wait for a return to life as it was before Alzheimer. People no longer know what that would be like anymore because the rising tide of Alzheimer's has been present for so many decades.

Notwithstanding the non-release of the results, I think it should still be understood that today was the day that changed everything. Often with science stories it is not overly obvious how results should be framed; usually there is a sense that studies say this and there are more studies on the way ... which makes for a murky interpretation.

Yet, it isn't necessary for the explicit number for Lucidity to be released for a celebration; we already know that it was effective. Two phase trials and a phase 2 trial and now another phase 3 trial have shown efficacy. taurx's initial press release explicitly reported that Lucidity substantially slowed decline across the AD cognitive impairment spectrum and that they now intend to go to regulators with these results. This qualitative assessment is good enough to start the celebration. The press release also noted that the treatment as given in Lucidity satisfied safety standard. This should be enough for those who are coping with dementing illness to now seek treatment with MB/LMTM.

Right to Try could and perhaps should now be invoked.
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Re: AD cured? taurx reports positive Lucidity results !!!!!!!!!!

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I had not carefully studied the history of the Lucidity trial. I had thought there would be a simple 50-50 split of the 598 enrolled patients between placebo and the treatment dose of 16 mg per day. Alzheimer trials usually are not that simple: Lucidity did not disappoint.

This is the write-up from alzforum:


"In January 2018, TauRx started another Phase 2/3 trial aiming to enroll 180 people with all-cause dementia and Alzheimer's disease, at 55 sites in North America, Belgium, Poland, and the U.K. The trial compares a six-month course of 4 mg of LMTM twice daily—the amount of LMTM previously admixed to "active placebo'' in the prior Phase 3 trials—to a different kind of placebo. Primary outcomes include 18F-FDG-PET imaging and safety; secondary outcomes include structural MRI, as well as measures of cognition and activities of daily living.

In September 2018, TauRx changed the trial protocol to add a third treatment arm of 8 mg LMTM twice daily, increase enrollment to 375, and extend dosing to nine months. Eligibility criteria were changed to accept only people with mild cognitive impairment due to AD, a Global Clinical Dementia Rating of 0.5, and a positive amyloid PET scan. Primary outcomes were also changed, to include a composite measure of cognition and function comprising selected items from the ADAS-Cog and ADCS-ADL scales. The trial was enlarged to 147 sites in North America and Europe.

Recruitment ended in October 2019. On November 5, 2019, the first of three listed primary outcomes was changed from change on 18F FDG PET to ADAS-cog 11. Also in October, the inclusion criteria were relaxed to once again include people with more advanced disease, from an earlier MMSE range of 20-27 to 16-27, from a CDR of 0.5 to now include CDR 0.5 to 2, and from excluding all epilepsy to including people with a single episode. Enrollment changed from 375 to 450, study duration from nine to 12 months."

https://www.alzforum.org/therapeutics/lmtm

That is just remarkably confusing. Clearly this exceeded my wildest expectations for such confusion.

Let me get this straight.

They started the trial as a phase 2/3 with 180 patients who are all-cause dementia and Alzheimer's with a 6 month treatment period at 8 mg per day with primary outcomes of PET and safety? and secondaries of cognition and ADLs.
They then added in 16 mg daily dosing and increased enrollment to 375 and went out to 9 months and changed eligibility to MCI with positive PET amyloid and then changed primaries to ~iADRS? Then recruitment ended and then they changed the primaries to ADAS-cog11 and they changed inclusion to include moderate AD Then they changed enrollment to 450 and changed duration to 12 months ... and then some time later they decided to go with 598 full enrollment?

That is very confusing! Where do you even start?

Something that I have found interesting is that one can work some of the numbers backwards to see how effective they though HMTM would be. For example, with 180 patients total which might result in ~70 completing patients, with SD=9.5 there would need to be a treatment effect of 3.5 ADAS-cog to reach 1.7% p-value. That seems remarkably unlikely. That isn't what the taurx publications reported happening at such an early time point. They apparently were also including "all cause dementia" which is problematic as this would add heterogeneity to the AD patient population. They were also using a 8 mg daily dose which was not found to be effective for a substantial proportion
of the patients.

Very unclear why they would use a FDG PET scan as a primary. ADAS-cog, ADCS-ADL etc. these are the go to instruments. Going with a biomarker when you can go directly to measures of real-world functioning is very odd.

They then added in 16 mg daily dosing which is the effective dose increased sample size to 375 and went out to 9 months. These are good changes, though it does start to make things complicated. How many of the patients in the trial only received 8 mg dosing? With 150 patients in placebo and treatment arms all on 16 mg for 9 months then even a 2 ADAS-cog benefit would give a 3.5% p-value. The problem is that there seems to be an extended placebo plateau that was seen in the phase 3s for the first part of the trials. The placebo patients started to enter large cognitive declines past the half-year mark. This adds in some risk as to when this decline would start up. Now they have promoted iADRS to the primary which makes sense and are including only those with a positive PET amyloid scan -- that is only those patients who actually have Alzheimer's; this is also a good move.

Then they changed to ADAS-cog11 as a primary-- also a goodish idea ... moved to include Moderate AD very good; Moderates were seen to have more benefit in the phase 3s. Increasing sample size to 450 also a good one as was going out to 12 month dosing. These changes would have really pushed the results over the line from possibly being somewhat marginal to unequivocal. Then they went to 598 which was perhaps slightly excessive, though nonetheless worthwhile.
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