Celebration Thread: Anavex273 Blarcamesine!

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J11
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Celebration Thread: Anavex273 Blarcamesine!

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ADAS-cog 2.png
I am not sure on the left how the trial was constructed. The figure makes it seem that at baseline there was a ~5 point separation between placebo and treatment. Usually you expect that there will be zero difference at baseline between placebo and treatment.


So much to celebrate!
It's not easy just keeping up with all of the phase 3s (completed and otherwise) and all of the celebrations as well!

A phase 3 for Anavex's Anavex273 (Blarcamesine) finished up to its primary completion date as of last month.
https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=6


Perhaps we will have a top-line result reported at AAIC 2022 in July/August?

A phase 3 for Rett Syndrome has already been reported and another is expected to reach
primary completion by the end of this year. Parkinson's research has already shown favorable results.
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Re: Celebration Thread: Anavex273 Blarcamesine!

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anavex 273 c.PNG
anavex 273 b.PNG
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Re: Celebration Thread: Anavex273 Blarcamesine!

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Where's the amyloid? There is no sign of amyloid in the top graphical abstract.

The middle figure on the bottom right notes that the result in AD was conditional on genotypes for rs1800866 and rs113895332/rs1143203. Full genome sequencing is included in the phase 3 AD trial so perhaps yet more genotypes will be found to be conditional.

Blarcamesine could be another large readout for 2022!


I am running out of unique party genres; this time I'll go with Vacation.

https://www.timeanddate.com/countdown/v ... nt=cursive
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Re: Celebration Thread: Anavex273 Blarcamesine!

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I have not delved deeply into Blarcamesine's approach to dementia management, though the phase 2b/3 is now about ready to report. The basic gist of it is that this could be a blowout topline readout.

I do not have a great deal of insight into how SIGMAR1 relates to AD; I have been almost singularly focused on thinking in terms of amyloid and how changes in amyloid relate to changes in cognition. SIGMAR1 is a mystery to me.

However, if there is celebration, then I need to be ready for it. I want to be ready with the party hats and an ample supply of cashews. Unfortunately, aside from the odd "WaHOos!" I do not think that I will be able to substantively contribute to the scientific discussion. Though clearly, stabilizing cognition in AD over a 48 week treatment interval would obviously capture my attention.

This year's CTAD could be close to a riot. There could be one schmunching after another. I am not completely sure about the exact timing for the topline for the Blarcamesine phase 2b/3, though it would not be that surprising if the announcement were to occur within the next month (i.e., about 1 month ahead of CTAD).

This is going to be so epic for all those people in the AD community. Once AD begins to progress it has been so devastating when there has been nothing to stop the advance. Blarca could offer powerful anti-dementing that might over some time frame largely halt progression.
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Re: Celebration Thread: Anavex273 Blarcamesine!

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So much to celebrate; it's difficult even keeping the countdowns up to date.

Here's the CTAD Blarcamesine phase 2b/3 countdown:

https://www.timeanddate.com/countdown/v ... nt=cursive
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Re: Celebration Thread: Anavex273 Blarcamesine!

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Re: Celebration Thread: Anavex273 Blarcamesine!

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Whoa! Blarcamesine appears to have hit the numbers!
https://www.anavex.com/post/anavex-2-73 ... -endpoints


ANAVEX®2-73 (BLARCAMESINE) PHASE 2B/3 STUDY MET PRIMARY AND KEY SECONDARY ENDPOINTS,

SHOWING STATISTICALLY SIGNIFICANT REDUCTION OF CLINICAL DECLINE IN GLOBAL CLINICAL STUDY OF PATIENTS WITH EARLY ALZHEIMER’S DISEASE

Robust, Statistically Significant and Clinically Meaningful Absolute Improvement in Cognitive Function as Measured by ADAS-Cog and ADCS-ADL

Key Secondary Endpoint CDR-SB Also Met, Demonstrating Statistically Significant Results


Plan to Meet with Regulatory Authorities to Determine Next Steps
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Re: Celebration Thread: Anavex273 Blarcamesine!

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The AD patients got BETTER? Wow!


https://finance.yahoo.com/news/anavex-2 ... 00796.html

Robust, Statistically Significant and Clinically Meaningful Absolute Improvement in Cognitive Function as Measured by ADAS-Cog and ADCS-ADL

Key Secondary Endpoint CDR-SB Also Met, Demonstrating Statistically Significant Results

Plan to Meet with Regulatory Authorities to Determine Next Steps

NEW YORK, Dec. 01, 2022 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) disorders, today announced positive topline results from its Phase 2b/3 ANAVEX®2-73-AD-004 clinical trial of oral ANAVEX®2-73 (blarcamesine) for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD). ANAVEX®2-73 met the primary endpoints ADAS-Cog1 and ADCS-ADL2 and key secondary endpoint CDR-SB3 with statistically significant results. Next step, in light of this data, is meeting with regulatory authorities to discuss this data in the context of ongoing development with an aim to bring this therapy to patients in Europe, Asia-Pacific, and the U.S.

ANAVEX®2-73 (blarcamesine) is an orally available, small-molecule activator of the sigma-1 receptor (SIGMAR1), which, data suggest, is pivotal to restoring neural cell homeostasis and promoting neuroplasticity.4

ANAVEX®2-73-AD-004 was a randomized, double-blind, multicenter, placebo-controlled 509 patient Phase 2b/3 study (randomized 1:1:1 to mid or high dose of ANAVEX®2-73 or placebo), for the treatment of early Alzheimer’s disease over 48 weeks. Top line data will be presented later today in the late breaking oral communication presentation at the Clinical Trials on Alzheimer’s Disease (CTAD) Congress 2022, December 1, 2022, at 4:30pm PT in San Francisco, CA. Further analysis of the data remains ongoing, and the Company plans to submit the data for publication in a peer-reviewed medical journal. The open-label extension study ATTENTION-AD will continue to follow participants over a 96 week period.

ANAVEX®2-73 treatment met the primary endpoints and reduced clinical decline on the global cognitive and functional scales over 48 weeks in the analysis of the Intent-to-treat (ITT) population.

ANAVEX®2-73 demonstrated visible improvement in patients with Alzheimer’s disease. Patients treated with ANAVEX®2-73 were 84% more likely, to have improved cognition by ADAS-Cog score change of -0.50 points or better from baseline to end of treatment than patients on placebo, Odds Ratio = 1.84 (p = 0.015). On average, patients, who improved cognitively with ANAVEX®2-73 treatment, improved by ADAS-Cog cognition score of -4.03 points. ANAVEX®2-73 treatment was 167% more likely to improve function compared with placebo, at a clinically meaningful improvement of ADCS-ADL score change of +3.5 points or better, Odds Ratio = 2.67 (p=0.0255). This reflects a robust improved and clinically meaningful outcome in cognition and function from baseline.
Additionally, treatment with ANAVEX®2-73 statistically significantly reduced cognitive decline, measured with ADAS-Cog, compared to placebo at end of treatment by 45%, representing a treatment difference in mean score change of -1.85 points (p=0.033).

ANAVEX®2-73 treatment also met the secondary endpoint of reduction in clinical decline of cognition and function assessed by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) compared to placebo, by a treatment difference in mean score change of -0.42 points (p=0.040), representing 27% reduction in the ITT population.

ANAVEX®2-73 (blarcamesine) was generally safe and well tolerated. The incidence of treatment emergent adverse events (TEAEs) was similar in the active and placebo arms with dizziness being the most common TEAE. TEAEs ≥7.5% threshold were predominantly mild or moderate. No clinically significant changes in vital signs, laboratory values and ECG parameters in active and placebo arms were observed. Safety findings in the study were consistent with the known safety profile of ANAVEX®2-73.

In addition to safety and efficacy demonstrated on the primary and key secondary endpoints, a pre-specified analysis of patients without SIGMAR1 gene mutation provides further confidence of the robustness of the SIGMAR1 activation in the treatment of neurodegenerative diseases. Approximately 80% of the total worldwide population lack a SIGMAR1 gene mutation.5 ANAVEX®2-73 was more efficacious in this pre-specified population. This effect is consistent with prior clinical trials of ANAVEX®2-73.6
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Re: Celebration Thread: Anavex273 Blarcamesine!

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Oh Yeah!

phase 2b/3
N= 509
measured at 48 weeks
oral dose

Co-Primary ADAS-Cog 45% reduction in decline difference of -1.85 points (p=0.033).
ADCS-ADL also hit this co-primary, though I am unclear about the numbers

Secondary 0.42 benefit on CDR-sb 27% reduction in decline over placebo p=0.04


Gene variants in Sigmar1 confirmed as inhibiting response.
80% of people lack these variants.
variant of interest rs1800866

also COMT rs113895332, rs61143203
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