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I’m curious what you propose caused the positive changes in the 6 patients over that 7 week time frame, improvements that were correlated with established GABA and glutamate biomarker levels?
And Rett patient improvements correlated with the objective biomarkers gaba and glutamate levels. Would seem tough to attribute that to placebo effect.
Enjoyed that perspective JJ.
And I’ll add to your point of reference that I still can’t find any material negatives with Anavex.
Instead I just see all of our new patents/IP, scientific conferences, investor presentations, peer-reviewed MOA supportive scientific publications this year, and the announced and presented and p/r’d initial very positive pk 7 week RS results in September, and the positive p/r announcement of the PRV and RS rare pediatric disease designation from the FDA this month, growing institutional ownership positions, and Dr M’s heightened excitement and confidence level during the recent 10/4/19 presentation at Janney, everything TO MY EYE seems to point towards a Company navigating full speed ahead with a strong tailwind.
It’s certainly a bizarre dichotomy with the fledgling market cap. But my working premise is that the Company is simply focused on achieving its goals and that the market/SP will be what it will be.
It could easily be argued that the steady and measured and quiet approach is (1) indeed the correct one during this methodical march towards regulatory approval, and (2) indicative of internal confidence in their compound(s) and inherent safety/efficacy to date.
GLTY
Published 11/19/19 re S1R therapy for PD, great find Georgejii.
This paper references two of Veronica Francardo’s papers; and she did the preclinical 2-73 research in Parkinson’s with the MJFF funds.
“The Sigma-1 receptor (Sigma1R)9 is a promising target for the development of therapy for Parkinson’s disease10,11,12,13”
11.
Francardo, V. et al. Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism. Brain: a journal of neurology 137, 1998–2014, https://doi.org/10.1093/brain/awu107 (2014).
13.
Francardo, V. et al. Pridopidine Induces Functional Neurorestoration Via the Sigma-1 Receptor in a Mouse Model of Parkinson’s Disease. Neurotherapeutics. https://doi.org/10.1007/s13311-018-00699-9 (2019).
https://www.nature.com/articles/s41598-019-53413-w
You’re incorrect.
The FDA collaborates with Ariana Pharma, “a provider of decision support software for pharmaceutical discovery, development and safety, in the agency’s efforts to improve the analysis of genomic data in support of personalised medicine” and Ariana’s CEO presented the below regarding our Anavex Alzheimer’s Disease 57 week results.
And also here’s the link to our initial Rett Syndrome US adult study positive efficacy results in the pk 7 week study, as illustrated and presented in September by Walter Kaufmann, leading researcher worldwide on RS and now our CMO and trial PI:
https://www.globenewswire.com/news-release/2019/09/16/1915810/0/en/Anavex-Life-Sciences-Announces-Preliminary-Clinical-Efficacy-Data-of-its-U-S-Phase-2-Clinical-Trial-of-ANAVEX-2-73-in-Patients-with-Rett-Syndrome.html
And as xena reminded you, multiple recent scientific peer reviewed publications support and validate our 2-73 MOA.
[cited from the October 2017 PK/PD presentation outlining Ariana’s & Anavex’s representations regarding dose/concentration relationships (from our 57 week ph2a AD participants):
http://www.anavex.com/my_uploads/ANAVEX2-73-PKPD-Phase-2a-2017.pdf
· Slide 3: in depth analysis using Ariana technology demonstrates “relationship between Anavex2-73 measured exposure and dose (PK) are consistent across study periods”
Slide 3: in depth analysis using Ariana technology demonstrates “strong drug concentration / response relationship revealed for key Alzheimer’s disease trial endpoints cognition and function, MMSE and ADCS-ADL (PK/PD). This relationship is consistent across multiple time periods”
· Slide 3: “same applies for the brain activity biomarker ERP (PK/PD)”
· Slide 6: across the 5 weeks and the 52 weeks their slides say that the achieved (check mark) “dose-effect relationship”
Slide 12: Ariana indicates “confirmed reliable inter-individual variability (dispersion) for the Anavex2-73 phase 2a study with 32 patient cohort” and that “this is confirmation that the sample of 32 patients of the Phase 2a provides reliable information regarding dispersion and as such allows for meaningful predictions for larger populations”
· Slide 13: Ariana indicates “relation between Anavex2-73 exposure and dose (PK) are consistent across administrations”
· Slide 14: “High Dose of Anavex2-73 correlates with exposure”
Slide 19: “ERP Biomarker Shows Significant Drug Response: P3a Amplitude Increases with Anavex2-73”
· Slide 24: through Ariana’s KEM Systematic Analysis, they found 83 rules (possible relations across variables, endpoints, PK parameters and time) and “97% of them showing coherent dose-response relation”
Slide 25: entitled “Robust Dose (Concentration) / Response Effect of Anavex2-73” and their KEM analysis provided “consistency for 6 main exploratory endpoints cognition, function and biomarker (MMSE, ADCS-ADL & EEG/ERPs) demonstrated through systemic exploration of the full data matrix”
· Slide 25: “97% consistency: MMSE, ADCS-ADL and EEG/ERPs: Identified relations show that high dose (concentration) is linked to improved response and low dose (concentration) to poor response”
Slide 26: chart shows that for our participants that achieved >4ng/mL blood concentration level (9 total) during the 57 week study, that 4 improved on the MMSE tests and 1 remained at baseline (5 out of 9 is a majority)
· Slide 28: “an increase of MMSE is a rare event.” And “a patient receiving a higher concentration of Anavex2-73 has a +110% (2.1 fold) chance of improving its MMSE during 57 weeks”
Slide 29: “KEM identifies strong non linear relations linking concentration with response for both MMSE and ADCS-ADL”
· Slide 30: High Anavex2-73 concentration linked to improved response consistently across all analytes and periods” and “both Anavex2-73 and metabolite show a consistent response across the 3 different time frames”
Slide 32: “KEM analysis has identified exclusion / inclusion criteria. Each criteria has the potential to improve MMSE / ADAS-Cog for mild to moderate Alzheimer’s patients treated with Anavex2-73” and “these criteria will be incorporated into the upcoming Anavex2-73 phase 2/3 trial”]
Where do you read in the below that our flight has been canceled?
https://www.anavex.com/anavex-life-sciences-receives-rare-pediatric-disease-designation-from-fda-for-anavex2-73-blarcamesine-for-the-treatment-of-rett-syndrome/
https://finance.yahoo.com/news/anavex-life-sciences-announces-publication-120000021.html?bcmt=1
https://www.anavex.com/anavex-life-sciences-issued-new-u-s-patent-for-composition-of-matter-covering-anavex2-73-for-the-treatment-of-alzheimers-disease/
https://www.anavex.com/anavex-life-sciences-announces-preliminary-clinical-efficacy-data-of-its-u-s-phase-2-clinical-trial-of-anavex2-73-in-patients-with-rett-syndrome/
8/7/19
“ANAVEX®2-73 (blarcamesine) Program Update:
Enrollments for the U.S. Phase 2 Rett syndrome study[1] and the AVATAR Rett syndrome study[2] of ANAVEX®2-73 (blarcamesine) are advancing with high priority.
The independent Data Safety Monitoring Board (DSMB) for the U.S. Phase 2 Rett syndrome study of ANAVEX®2-73 (blarcamesine) completed its recent pre-planned review of the preliminary Phase 2 efficacy and safety data. Upon review of the most recent data, the DSMB made the recommendation to continue the study without modification.
The enrollment of the Phase 2 ANAVEX®2-73 (blarcamesine) Parkinson’s disease dementia (PDD) study[3] is proceeding well and is getting closer to reach completion. At the request of investigators in order to offer all participants of the clinical study access to ANAVEX®2-73 (blarcamesine) a voluntary extension of this study is in preparation including microbiome assessment.
Enrollment for the Phase 2b/3 ANAVEX®2-73 (blarcamesine) Alzheimer’s disease (AD) study[4] is proceeding as At the request of investigators in order to offer all participants of the clinical study access to ANAVEX®2-73 (blarcamesine) a voluntary extension of this study is planned.
A recent peer-reviewed scientific publication titled, Neuronal Sigma-1 receptors: signaling functions and protective roles in neurodegenerative diseases, details the mechanism of action of Sigma-1 receptors (S1R) and references ANAVEX®2-73 among the relevant S1R ligands. The paper summarizes: “In conclusion, S1R is incredibly versatile in its ability to foster neuronal homeostasis in the context of several neurodegenerative disorders.”[5]“
https://www.anavex.com/anavex-life-sciences-announces-initiation-of-the-excellence-anavex2-73-rs-003-clinical-study-in-pediatric-patients-with-rett-syndrome/
https://www.anavex.com/anavex-life-sciences-receives-positive-opinion-for-orphan-designation-from-the-european-medicines-agency-for-anavex2-73-for-the-treatment-of-rett-syndrome/
https://www.anavex.com/anavex-life-sciences-presents-new-clinical-data-identifying-gut-microbiota-biomarkers-associated-with-improved-clinical-response-in-patients-treated-with-anavex2-73-at-2019-alzheimers-a/
https://www.anavex.com/rett-syndrome-association-of-australia-and-anavex-life-sciences-announce-initiation-of-the-phase-2-avatar-clinical-study-in-patients-with-rett-syndrome/
https://www.anavex.com/anavex-life-sciences-reports-publication-of-new-data-that-show-anavex2-73-induces-cellular-recycling-process-linked-to-the-prevention-and-treatment-of-age-associated-diseases/
https://www.anavex.com/anavex-life-sciences-announces-the-appointment-of-walter-e-kaufmann-md-as-chief-medical-officer/
“.. this is what is in the works
Why Institutional is accumulating while retail dumps..”
It makes sense to me. I didn’t know about it until jwc3 and xena discussed it last month.
If Anavex was not applying for AU provisional approval then I’d be pissed. And if our compound’s “preliminary clinical data” doesn’t meet the TGA’s standards then something’s rotten in Denmark (no offense to our Dane).
That’s right, and I believe first approval may’ve been in April 2018, then keytruda obtained a provisional approval in July 2019 too.
The provisional approval program itself was officially put into effect in March 2018.
Good point McMag, and based on the reading of the new AU rules, as others such as jwc3/xena have alluded to before, it would seem somewhat absurd at this point if Anavex did not apply.
If the efficacy results we’ve heard and seen to date in our preliminary AD and RS studies, including quotes from our own Australian AD trial PI in interviews still hold true, then what else could the TGA want in terms of this new provisional approval program??
And we apparently not only have a safe compound, but also one that our AD participant caregivers reported positive RWE quality of life improvements as well.
You’re probably right, he likely moved the RS and PDD to AU as part of a plan to apply for this new AU provisional approval based on the “preliminary clinical data” in those trials and indications.
Absurd to not apply based on what we know at this time.
JJ, I guess the question is whether 2-73 meets this definition currently:
“Approval through the provisional pathway will be on the basis of preliminary clinical data where there is the potential for a substantial benefit to Australian patients.”
Basically: PRELIMINARY CLINICAL DATA that can form the basis for “improved efficacy” and a “better safety profile”.
That’s what they’re asking for in order to grant Provisional Approval in the land Down Under.
My personal opinion based on known-knowns would be that yes we should qualify under these new rules based on our 4+ years of AD trial data in Australia along with our various available open label extension data in PDD and RS trials. [That is IF the Company can illustrate how they plan to get AD patients up to the > 4ng/mL blood concentration level.]
It just has to be “preliminary clinical data”. I guess the question is if/whether Anavex has or will apply under these new 2019 rules.
Seems a good question for one of our hard-hitting conference call analysts!
ALSO “Sponsors are strongly encouraged to organise a pre-submission meeting with the TGA to discuss planned applications for provisional determination.”
QUESTION: Didn’t Dr Missling travel to Australia in October? Did he really fly around the world just to give a 20 minute presentation at an Australian scientific conference? Could be have been there for a pre-submission meeting for AD?
https://www.tga.gov.au/provisional-approval-pathway-prescription-medicines
“As part of the Government's response to the Review of Medicines and Medical Devices Regulation (MMDR review), we are implementing a pathway for the provisional registration of prescription medicines. Approval through the provisional pathway will be on the basis of preliminary clinical data where there is the potential for a substantial benefit to Australian patients.”
And
“The eligibility criteria are:
New prescription medicine or new indications medicine
For treating a serious condition
Favourable comparison against existing therapeutic goods
Major therapeutic advance
Evidence of a plan to submit comprehensive clinical data.”
https://www.tga.gov.au/first-provisional-approval
Furthermore:
“Justification of significant improvement in safety or efficacy
You must demonstrate, based on preliminary clinical evidence, that the medicine provides a clinical benefit over existing therapeutic goods for the indication that is the subject of the determination application (for either treatment, prevention or diagnosis of the condition) by addressing either of the following:
improved efficacy for the entire population relevant to the therapeutic indication
OR
a better safety profile for the entire population relevant to the therapeutic indication
Base the supporting evidence on clinical trial data. Surrogate endpoints require a justification, as explained in Clinical data supporting provisional determination.”
If clarity is what the market is looking for then today’s updated clinical trials dates shed light on where enrollment is and when full enrollment is expected.
I’m also expecting specifics from the Company by early Dec on exactly what’s going on with enrollments in all of the trials, and information about the PDD extension, and how many patients have been moved to the open label extensions in each trial and any known publication date for the AD blarcamesine peer reviewed publication deep dive.
A 208 week RWE/efficacy update for our ph2a AD participants would also be welcomed.
And when the world’s leading Rett Syndrome researcher tells the European Rett conference and RS community in September that Anavex 2-73 blarcamesine on a low 5 mg liquid dosage significantly improved the initial 6 patients and their behaviors on a biomarker correlated basis, my hunch is that Dr. Kauffman received many new requests for patients to be allowed into the trial(s).
That seems very reasonable to me at least.
Perhaps the reasons relate to expanding PDD sites in Australia from Spain mid 2019. And over enrollment in RS.
They’ll assumably provide clarity on Dec year end cc or earlier p/r.
Clinical trials website finally updated and the completion dates have been pushed back between three and seven months for RS and PDD. C’est la vie.
https://clinicaltrials.gov/ct2/show/NCT03774459?term=Anavex&draw=2&rank=2
Actual Study Start Date : July 9, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : July 31, 2020
https://clinicaltrials.gov/ct2/show/NCT03758924?term=Anavex&draw=2&rank=4
Actual Study Start Date : February 28, 2019
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : May 31, 2020
Regarding your prior message, I concur with your thought McMag:
“Because the ...........’s are on
Anavex for a reason other than shorting a poorly managed or over valued stock..”
There is only around 150 million of market value left on the short bone here. Shorts could instead make BILLIONS shorting certain inflated and artificially pumped big pharma names (with a MUCH lower risk of a binary large short loss).
The psychological and financial warfare online against Anavex is designed to stunt the growth and clinical progress and fundraising abilities.
AND in my opinion to condition the large majority of retail-held shares to be freed up on the first future price spike.
Whether it’s 1 or 2 billion market cap or even lower, the goal is to wear us down and condition us to view a relatively low stock price as a point to cut bait and exit positions with some nominal gain.
The machine does not want us to succeed, first and foremost, but if we do, they certainly want to buy up our retail held positions at low prices.
Again IMO there’s very little chance that retail shorts would be still trying to short down this last 150mm of value based on all of the positive momentum for Anavex.
It’s absurd otherwise, which is why I believe the Company should be exploring the derivation of the attacks.
My opinion and informed speculation only.
GLTY
You’ve quite the way with words, Jimmy. Good stuff.
Nidan, by the way Peter has a few interesting theories about the importance of Anavex’s upcoming December CTAD presentations:
https://piotrpeterblog.com/2019/11/04/unified-alzheimers-theory-avxl-is-doing-what-no-company-has-ever-done-blarcamesine/amp/?__twitter_impression=true
https://piotrpeterblog.com/2019/11/14/avxl-some-other-musing-on-ctad-2019-upcoming-presentation-blarcamesine/
https://piotrpeterblog.com/2019/11/11/augmented-phase2a-data-validates-blarcamasine-as-alzheimers-greatest-hope-even-before-phase-2-3-results-avxl/
I couldn’t have summed it up half as well; thanks for making sense of the nonsense that is seemingly our current CNS drug development system, and the why/how of Anavex’s steps in AU/Spain.
As you alluded to, case in point being the NIH/ACTC’s puzzling selection of BAN2401 and elenbecestat as its trial candidates to date.
Of course Eisai And Biogen announced in September 2019 that they’d discontinue Phase III Clinical Studies Of the BACE inhibitor Elenbecestat in early Alzheimer's Disease, including discontinuing the extension study, based on the Data Safety Monitoring Board recommendation. They’re apparently still pushing ahead with ban2401 (which is similar to the futile aducanumab beta-amyloid hypothesis).
This despite the fact that Anavex has been front and center at annual Alzheimer’s Disease scientific conferences the past few years with late breaking oral presentations illustrating biomarker correlated and dose/concentration dependent stabilization & improvements in AD patients at their therapeutic blood concentration levels). Presented and illustrated by the Precison Medicine data analysis firm, Ariana Pharma. (“The US Food and Drug Administration is collaborating with Ariana Pharma, a provider of decision support software for pharmaceutical discovery, development and safety, in the agency’s efforts to improve the analysis of genomic data in support of personalised medicine”)
As you say “The system is hopelessly rigged and is non productive”. You hit the nail on the head there.
BTW let’s hope the EMA will follow through on this guidance they issued in early 2018:
https://www.reuters.com/article/us-healthcare-alzheimers-europe/europe-follows-fda-with-plans-to-help-early-alzheimers-drugs-idUSKCN1GC2BU
Perhaps these institutional investors significantly added after hearing recent Anavex presentations, such as the one at Janney on September 10th.
And after our three positive p/r’s in July & September regarding the significant efficacy and behavior outcomes for our 1st 6 Rett patients (biomarker gaba and glutamate correlated per Dr Kaufmann).
https://www.anavex.com/wp-content/uploads/2019/09/Janney-Audio-Presentation-Sept-2019.mp3
And no, I do not believe the bulk of the adds were index based. Blackrock now owns over 5% of the outstanding shares of Anavex. I do not think an index position would entail purchasing over 5% of the Company.
Thanks nobrainer, I never said I was smart, just handsome and somewhat charming
Yes, something tells me that the medical & treatment Establishment (and its prideful researchers who helped waste billions of research resources for 3 decades) does not want a safe compound (that would work across numerous CNS disease indications) to be approved by a small little-known biotech which would cause patients to improve or stabilize from baseline.
The status quo is working just fine by them.
Something also tells me that the Establishment and Big Pharma have agents of influence embedded within our government and our decision-making bodies and financial markets to safeguard their positions.
IMO of course.
That’s a great find Georgejii, date of patent October 15, 2019.
Also the important Composition of Matter patent No. 10,426,754 was announced on October 2, 2019.
Has been a very productive year for Anavex with positive developments across the board, much to the chagrin of our daily detractors here.
GLTY
Patent History
Patent number: 10441563
Type: Grant
Filed: Oct 19, 2015
Date of Patent: Oct 15, 2019
Patent Publication Number: 20180177756
Assignee: ANAVEX LIFE SCIENCES CORP. (New York, NY)
Inventors: Missling U. Christopher (New York, NY), Durrant Cameron (Califon, NJ)
Primary Examiner: Sahar Javanmard
Application Number: 15/571,877
Posted today by the Rett Syndrome Association of Australia on Facebook:
“Another leap forward by Anavex after receiving Rare Pediatric Disease Designation which basically means they can receive priority review from the FDA.”
They also linked the p/r:
https://www.anavex.com/anavex-life-sciences-receives-rare-pediatric-disease-designation-from-fda-for-anavex2-73-blarcamesine-for-the-treatment-of-rett-syndrome/?fbclid=IwAR2-CTYMuhWmiyLVtriI6bJiytpP9ZKdCRJrnjvKT7WmbUlqv8tFqZ8NQ0I
Thanks for that chart Roy showing the 32 PRV issuances by FDA since 2007 passage.
Here’s updated FDA guidance from
7/29/19:
https://www.fda.gov/news-events/fda-brief/fda-brief-fda-updates-draft-guidance-rare-pediatric-disease-priority-review-voucher-program
““Despite continued progress, too many rare diseases still have no approved therapies. One of the FDA’s top priorities is to provide incentives and clear advice to medical product developers so that they can advance innovations that can help address the significant unmet medical needs for patients with rare diseases. This holds especially true in rare diseases that impact children,” said Janet Maynard, M.D., director of the FDA’s Office of Orphan Products Development, which along with the Office of Pediatric Therapeutics, oversees the Rare Pediatric Disease Designation program. “One program in place intended to advance the development of drugs and biologics for certain serious and life-threatening rare pediatric diseases is the Rare Pediatric Disease Priority Review Voucher Program. Under this program, a drug company that receives an approval for a drug or biologic for a rare pediatric disease may qualify for a voucher that can be redeemed to receive a priority review of a subsequent marketing application for a different product. To provide clarity and advice to drug developers, today we are issuing an updated draft guidance about how this program works. This updated draft guidance reflects input from rare disease and pediatric experts from across the agency, highlighting our commitment to addressing the needs of patients with rare diseases. When finalized, this draft guidance will provide the agency’s current thinking regarding the updated definition of rare pediatric disease and explain the statutory requirements to earn a rare pediatric disease priority review voucher.””
That’s very interesting indeed... I looked that up as well and Wikipedia (I know I know) says that there’ve only been 14 priority review vouchers awarded through 2017.
4 for tropical diseases and 10 for rare pediatric diseases.
Whether it’s 32 or 14 since the 2007 passage, it’s still a VERY encouraging sign IMO.
“As of 2017, fourteen priority review vouchers have been awarded, four for tropical diseases, and ten for rare pediatric diseases. The first priority review voucher was awarded in 2009 to Novartis for its approval of Coartem. The next voucher was not awarded until 2012.[2][8]”
https://en.m.wikipedia.org/wiki/Priority_review
Today’s news is one of several reasons as to why I added to my position this morning. Seems to indicate that there’ve been constructive meetings with regulators since September’s positive initial Rett results were presented.
I personally am still only able to find positive news and scientific developments for Anavex, including various supportive peer-reviewed publications confirming our unique MOA, across numerous CNS disease indications (areas of significant unmet need).
Just my personal opinions of course.
GLTY
Strong move recently; thanks Jimmy667 for the tip last year around $12/share.
Last quarterly call was impressive as well.
https://www.google.com/amp/s/www.fool.com/amp/earnings/call-transcripts/2019/08/05/arrowhead-research-corp-arwr-q3-2019-earnings-call.aspx
“Arrowhead price target raised to $59 from $46 at B. Riley FBR B. Riley FBR analyst Mayank Mamtani raised his price target for Arrowhead Pharmaceuticals to $59 from $46 after hosting meetings with management. The Landsat came away "incrementally encouraged" with the strength of data being presented for Arrowhead's three lead RNAi programs "aimed at large population diseases," including hepatitis B and mixed dyslipidemia. He sees a "healthy catalyst profile" for Arrowhead shares and reiterates a Buy rating on the name.”
Read more at:
https://thefly.com/permalinks/entry.php/id2993375/ARWR-Arrowhead-price-target-raised-to--from--at-B-Riley-FBR
And for the record I am a long term shareholder, not a trader, and I am here to provide my honest opinion and analysis based on the facts as I know them to be, so as to make sense of the current state of affairs of a company that I own and that I truly hope will succeed.
I could not have been more clear that these are my personal opinions and analysis as it pertains to recent events and public presentations.
Glad to recap my personal conjecture and opinion, that with the backdrop of:
• the very confident and clear tone and tenor of Dr M’s investor presentation on 10/4/19 (many others expressed similar thoughts about the more confident presentation and clearly-described efficacy references during same), which I just relistened to yesterday
• and with IMO the 2 very positive efficacy-related p/r’s in September 2019 regarding our preliminary 6 out of 6 significant biomarker-correlated Rett Syndrome blood level GABA and glutamate and behavior improvements in our first 6 RS patients,
• combined with the corresponding highly visible European Rett conference presentation in Finland by the world’s leading RS researcher Dr Kaufmann which outlined on a global stage the same significant 2-73 Rett Syndrome biomarker and behavior improvements in those 6 out of 6 patients on just a low 5mg liquid dosage (which in turn IMO must’ve been expected to give hope to the Rett Syndrome and scientific community)
It is then with the above in mind that I personally form my opinion and position that the real-time and very valuable efficacy/safety/behavior/biomarker-correlation data on these OLE participants (extension data which Anavex has had In its possession & analyzed for many months/years in RS/PDD/AD) must then be supportive of their MOA/efficacy thesis.
Again that’s my take, obviously opinion/conjecture-based, which I’m entitled to do based on available information.
Wouldn’t you agree that it makes
sense that our Rett Syndrome study participants’ extension results since 6/25/19 are likely similarly-and-significantly-positive in efficacy and behavior and biomarker-correlated (similar to the 7 week results p/r’d by Anavex on 9/16/19) in light of the above backdrop?
If not, then one must either assume (a) the 3 months of RS extension results were not available/analyzed in real time (which goes against the definition of open label and uncontrolled extension studies); or (b) that our highly-decorated CMO would present and release information in September that is inconsistent with the available 3 months of extension results.
You may choose to not read the tea leaves the same, or at all. Personal choice of course.
Okay great, thank you, I likely wasn’t clear originally.
The point of it was simply that I do believe the OLE real time data and dose/response/behavior measurements and GABA glutamate blood levels (during the extension period only) is currently available to the Company and that this data must be supporting their MOA/efficacy thesis, for reasons I’ve editorialized earlier. My words not yours.
Enjoy your Saturday
Appreciated the reply, but I’ve yet to find anything that says that Anavex would have no access to the testing results of its OLE participants during each’s extension period “until the last controlled trial’s participant has completed dosing”; that makes no sense to me, and I cannot find that type of limitation stated anywhere.
I understand the bias limitations of such data in an open label extension, but how are Anavex and its trial investigators supposed to monitor periodic safety and efficacy measurements during the extension if they have to wait until all of the other remaining controlled-study participants have completed their controlled dosing?
If enrollment in an AD study takes 2 years in a large study, and participants immediately transition to an OLE after each’s controlled dosing, then you believe that the sponsor and trial investigators cannot access and analyze that 1st extension patient’s OLE performance and measurements until 24 months after they start the OLE?
With all due respect I don’t think that’s the case.
“ Open label extension studies typically follow a double blind randomised placebo controlled trial of a new drug. At the end of the double blind phase, participants are invited to enrol in an extension study. The study will normally be longer than the randomised trial (two years is not uncommon but they often continue until the drug is licensed). All participants in the extension study are given the study drug, and both they and the investigators know this. The objective is primarily to gather information about safety and tolerability of the new drug in long term, day to day use.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200598/#__sec1title
Journal article regarding OLEs, while addressing inherent bias issues in such an extension, which I concur, I cannot find any mention of any limitations on access to testing and monitoring results on OLE patients by the sponsor “until after all patients have completed the random controlled trial dosing”.
http://www.jrheum.org/content/jrheum/33/4/642.full.pdf
Example of an OLE below; again I see no mention of limitations on testing and analysis until all blinded participants have completed their dosing.
https://clinicaltrials.gov/ct2/show/NCT00991757
“Detailed Description:
333369EPY3004 is the open-label extension study that follows the double-blind studies 333369EPY3001 and 333369EPY3002 (NCT00425282 and NCT00433667, respectively). In an open label study such as 333369EPY3004, both the physician and the patient know the name of the assigned study medication. In a double blind study such as 333369EPY3001 and 333369EPY3002, neither the physician nor the patient knows the name of the assigned study medication. Patients who complete the double-blind treatment phase of studies 333369EPY3001 and 333369EPY3002 will be eligible to enter the open-label extension study 333369EPY3004 during which patients will transition through a blinded period to an open-label period with carisbamate (also referred to as RWJ-333369). There will be a blinded transition during which patients will take blinded study medication; after this, patients will then take unblinded, open-label study medication. No patients will receive placebo during the open-label extension. Safety assessments include the monitoring of the frequency, severity, and timing of adverse events, clinical laboratory test results, 12-lead electrocardiogram (ECG) recordings, vital signs measurements, physical and neurologic examinations, the Physician Withdrawal Checklist for symptoms of withdrawal for those patients who taper and/or discontinue study drug, and pregnancy tests for females of childbearing potential. Seizure counts will be obtained at every visit. A Quality of Life in Epilepsy questionnaire will be administered during the study. There is no statistical testing hypothesis for this study. Detailed Description update,5 Oct 2009. The Sponsor in conjunction with the DSMB agreed to amend the protocol to withdraw patients who develop signs of a drug hypersensitivity reaction.”
And that’s just for the Alzheimer’s indication. Makes it easy to understand why Anavex seems to be treading lightly and methodically to be sure they get this right.
Exactly
Great thanks that’s how I view it as well, and the efficacy/safety/behavior/biomarker-correlation data on these OLE’s are very valuable and we’ve had real time access to same for months now in RS/PDD and for years now in AD.
All good news & it provides an excellent backdrop to what said OLE data must be showing (when hearing M’s confident tone/tenor on 10/4/19 presentation, as well as Dr Kaufmann’s very positive Rett Conference presentation and two similarly positive p/r’s in September).
My 2 cents worth at least.
I think I follow, however, isn’t it true that if PDD patient #1 finished the controlled trial dosing in May 2019 and immediately patient #1 entered the PDD extension in May 2019, and the last patient #120 enrolled in the controlled trial in October 2019 for example, wouldn’t Anavex have access (today on November 1st) to the extension baseline data on patient #1 from May 2019 to date in an OLE trial?
For instance patient 1’s starting baseline condition in May and additional data/efficacy for patient 1 since May in their hands right now?
They would not have to wait for the entire trial’s unblinding to know what has occurred with patient 1 from May to today in the OLE, correct?
That’s my understanding of how an OLE works.
It’s after midnight in Denmark. Time for your brain-cleansing sleep.
Excellent post Georgejii, thank you very much
Gotcha and I agree they won’t have access to baseline data before the original controlled trial dosing but I believe they would at the start of the of the OLE; which to me still is very valuable as they can have real time access to cause/effect of various measures during the OLE term. Have a good one
If they’re able to do testing of efficacy and behavior during the extension period, I think it makes sense that they could do a baseline test at the start of extension dosing too.
Thanks gernee and I’ve previously read about the typical structure of these OLE trials; here’s one article that discusses them.
First I’m fairly certain the patients are measured at the start of the OLE for a baseline. That’s my understanding at least.
Also generally I’ve read that participants that agree to an extension have to start right away after the blinded trial dosing ends.
http://www.appliedclinicaltrialsonline.com/spotlight-open-label-extension-studies