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Perhaps I was being a little too excited with my "it works" exclamation. What the abstract says though is that in the lab A2-73 did indeed do what they were hoping and expecting.
We do not know if A2-73 will halt the progression or even partly or fully reverse MS. For that we need clinical trials.
I would say the implication at this point is that clinical trials in MS will be initiated by someone. Will that someone by Biogen or as I suggested in another post Teva, Celgene, Anavex or some other partner, I do not know.
http://www.professionalabstracts.com/ectrims2017/iplanner/#/grid
From the planner 27th Oct, Hall B at 14:00-15:30
Parallel Session 14: Remyelination: from biology to clinical trials
The bottom of the iceberg is beginning to surface!
So is Teva or Celgene more likely going to be our MS partner?
Celgene
SUMMIT, N.J.--(BUSINESS WIRE)-- Celgene Corporation (NASDAQ:CELG) today announced that its phase III RADIANCE trial, evaluating the efficacy and safety of ozanimod, an investigational oral, selective S1P 1 and 5 receptor modulator, in patients with relapsing multiple sclerosis (RMS), met the primary endpoint in reducing annualized relapse rate (ARR), compared to weekly interferon (IFN) ß-1a (Avonex®).
Our work in MS is not confined to Copaxone® and the relapsing forms of MS. Patients with progressive forms of the disease currently have no approved treatment options. We have an extensive research program investigating a new compound called laquinimod, which we believe has a neuro-protective capability. We are developing laquinimod for both relapsing and progressive forms of MS, in the hope that this new potential medicine will offer patients a much needed option in the treatment of progressive forms of MS.
Ladies and Gentlemen, it works!
238 - Sigma 1 receptor agonists as potential protective and reparative therapy in multiple sclerosis
R.P. Lisak, L. Nedelkoska, J.A. Benjmains Neurology, Wayne State University School of Medicine, Detroit, MI, United States
Objectives: Determine if sigma-1 receptor (S-1R) agonists can provide protection for oligodendrocytes (OL), OL precursors (OPC) and central nervous system (CNS) neurons (Neu) and promote repair. Background: S-1R are endoplasmic reticulum (ER) chaperones upregulated during ER stress, and also regulate calcium homoeostasis via inositol triphosphate at the ER-mitochondrial interface. We reported that dextromethorphan (DM), a S-1R agonist and weak NMDA receptor (NMDAR) antagonist, protects OL and OPC from toxic effects of molecules important in the pathogenesis of multiple sclerosis (MS) and increases OPC proliferation. Other groups have found inhibition of an animal model of MS by DM and another S-1R agonist. We sought to examine the potential protective and reparative effects of ANAVEX2-73, also a S-1R agonist, an NMDAR antagonist and a weak muscarinic agonist, unrelated to DM, on OL, OPC and Neu and extend our studies of DM to Neu. For both ANAVEX2-73 and DM we investigated if protection was due to agonism of S-1R.
Methods: Cell cultures containing >90% OL, OPC or Neu were prepared from neonatal rats and were incubated with staurosporine (apoptosis), glutamate (excitotoxicity), H2O2 (reactive oxygen species; ROS), quinolinic acid (inflammation) or additional medium (control) with or without DM or ANAVEX2-73 (provided by ANAVEXTM Life Sciences Corp, under the SIGMACEPTOR (R) program). Neu cultures were incubated with the same toxic molecules with/without ANAVEX2-73 or DM. We incubated OPC with ANAVEX2-73 and evaluated proliferation as well as maturation.
Results: We found that ANAVEX2-73 inhibited death of OL, OPC and Neu induced by the toxic factors and confirmed that DM also protected Neu as well as OL and OPC. Pretreatment of cultures with S-1R antagonist BD1047 inhibited the protection provided by both ANAVEX2-73 and DM. As reported earlier for DM, ANAVEX2-73 increased OPC proliferation assessed by uptake of a uridinie analog (BrdU). ANAVEX2-73 differed from our published findings with DM as it also increased maturation of OPC to more mature OL based on expression of phenotypic markers.
Conclusions: ANAVEX2-73 and DM protect OL, OPC and Neu from several toxic molecules involved in pathogenesis of MS. Protection appears to be dependent on signaling through S-1R. Both ANAVEX2-73 and DM increase OPC proliferation. ANAVEX2-73 also accelerates OPC maturation to OL. S-1R agonists could provide both protection and help with repair in MS.
Disclosure:
Robert Lisak: Grant funding from Teva, Speakers List: Teva; Consulting: Teva, Syntimmune, Celgene and RedHill Biopharm.
Liljana Nedelkoska: Nothing to disclose
Joyce Benjamins: Nothing to disclose
Research funded by the Parker Webber Chair in Neurology, Wayne State University/DMC Foundation. ANAVEX2-73 supplied by ANAVEXTM Life Sciences Corp.
Do we have a competition going now?
However many AVXL shares anyone owns, I wish good luck to all and most of all I hope the drug works for those who really need it!
Has he actually said dosing did not change from part B to C, the new 104 week extension trial? It would be good to know where he said that, thanks.
I'm impressed!
I believe I know the company you are referring to, which has that and another horse running both of which I rate with a good chance of approval!
Why is that even a question?
How many times has the company now confirmed in writing and verbally that 3 trials are starting this year: Rett P2, Parkinson's P2 and Alzheimers P2/3.
If you question that, which is fair enough, then it can only imply that the company must be lying or is just incompetent and frivolous with information.
Could be the case for sure. However, as it will be a P2/3 trial, I suspect there will be further dose differentiation in the P2 part informed by the KEM data being produced now. This will adaptively inform the doses needed for each arm for confirmatory outcomes as we slide seamlessly into P3.
More data, as promised by Missling, could by inclusion of DNA, RNA and gut biome data in the KEM analysis and perhaps also PART C longitudinal data. I mean, what else could it be?
Lol, I know even less about football than medicine. Anyway, I think I agree with you.
Thanks. I am impressed if you are fishing out all the links and quotes mainly on a phone to post here. It would drive me nuts to try, so kudos.
Of course. The important thing here is an emphasis on merits, as opposed to the many previous phase 3 trials that failed because they did not analyse their phase 2 data properly. In fact they could only do post hoc subgroup analysis because their trial design was not adaptive.
You see, medicine is tricky!
But but but, even if the 'statistical thing' from other studies has indicated improvement in patients based on data, in reality there was no clearly apparent real-life improvement expressed by patients themselves, their families and carers.
This is the sentiment we heard from MacFarlane and now Dr. Perry.
If you really care about this and many other great question - Can I ask, why do you suggest others should write to Dr. Perry in place of yourself?
I take it you are being sarcastic
It was though a cringe-worthy experience to stop, reverse and start the tape, while trying to capture and transcribe with the short memory of my ageing brain.
I listened too and took the following sentiment from it.
What Dr. Perry is saying is what we have also heard from MacFarlane. Namely, that apart from looking at the statistical thing, patients are actually improving, which have never before been seen. Only a slight decrease in the rate of decline.
Here is what Dr. Perry actually said as close I can transscribe it. Check for yourselves, always good to ensure what is being quote here is accurate and in context.
"Further it is important to note that the data that is shown, I'm talking about the statistics thing, that this approach actually has been effective in benefiting patients, they are actually improving. That has not been shown in any prior studies, even at the phase 2, it has always been instead a focus on the rate of change in decline. The sort of Aricept type model, which does benefit patients and families, but the results are very narrow and limited.
The most exciting part about this is the personalised medicine approach. Instead of grouping everyone together, people are looked at more individually and then data mining is used to, objectively and unbiasedly, be able to analyse subgroups, and this has a lot power compared to the approaches used for subgroup analysis after the fact post hoc analysis. What is being done here is looking at each of the data and is really compelling. There is quadrant analysis, which I have never seen applied to Alzheimer's disease, [that] shows a sub category of patients that actually improve and it is related to dose response. Well this doesn't still prove that this is going to be an effective drug, but it does show that the drug merits further study in phase 3. Further it suggest that the chance of phase 3 failure, which is 99.6, if not more because there has been some really recent failures, maybe 99.8% of drug trials in the last decade or so have failed, is because they haven't analysed the phase 2 drug data correctly. This sets a new standard for that type of analysis."
The purpose of the Ariana KEM analysis is to design the next trial optimally by knowing which patient profiles will respond well and stratify trial arms accordingly.
This is a new and intelligent way to reduce the risk of P3 trial failure, as per D. Perry on the call. So far we have only seen this Precision Medicine approach at work in Oncology, with Anavex being the first to take this approach together with Ariana in a CNS disease and then as complex as Alzheimers's.
This is quite different from the notion that data mining is being employed in a desperate attempt to squeeze plausible efficacy out of less than good results.
Medicine is tricky!
I think tom123 would say today's larger volume is not born out in the price action.
In fact despite the price increase, the Chaikin Oscillator has turned sharply negative today.
There is no doubt manipulation is rampant here.
This will not stop until we get, hopefully, positive trial results in Rett.
In my mind your statement:
@Investor2014: If randomization was appropriate then there is no reason to expect that the AVERAGE dose was any different between the 1st and 2nd period (slide 7)
Yep, I overlooked the Source.
Thanks for the extra commentary on slide 19. However, we have to remember the switch in dosing between patients in the 1st and 2nd period (slide 7).
We don't know the profile (no KEM selection quite yet) of each patient and exactly how they may respond. Nevertheless, I think it may be expected that improvement initially accelerates and then improves more gradually for responders over time.
Slide 18
"20 subjects: P3a amplitude is associated with verbal memory performance"
So is that how many patients were left at 57 weeks?
I continue to like the risk/reward ratio.
As I heard Missling, in Part B patients had continued on the dose they where on in Part A. The strong correlation coherently across all measures were that those on the higher doses continued to improved and those on too low doses did not.
The way Missling replied would imply no LPC tapping, so where is the funding coming from, Australia?
Anavex will host a conference call at 8:30 a.m. ET today, October 12, 2017. The call will be webcast live at http://www.wsw.com/webcast/cc/avxl2 and slides are accessible through the investor relations section of the Company's website at www.anavex.com. To join the call live via telephone dial 1-866-866-1333 within the United States or 1-404-260-1421 from outside the United States. A replay of the call will also be available for a period of three months through the Company's website shortly after the call.
Just been through the slides. I think we have a winner folks!
The PR says more data at CTAD.
"The stock market is a device for transferring money from the impatient to the patient." -- Warren Buffett.
BAM!!!
Press Release: Anavex Life Sciences Reports PK and PD Data from Phase 2a Trial of ANAVEX(R)2-73 in Mild-to-Moderate Alzheimer's Disease Patients; Conference call today at 8:30am ET
Anavex Life Sciences Reports PK and PD Data from Phase 2a Trial of ANAVEX(R)2-73 in Mild-to-Moderate Alzheimer's Disease Patients; Conference call today at 8:30am ET
ANAVEX2-73 demonstrates desirable PK/PD properties, describing the relationship between drug concentration and the effect observed
Anavex is incorporating advanced Artificial Intelligence platform for the analysis of Phase 2a results with the aim to increase the chances of success in forthcoming Phase 2/3 study
NEW YORK, Oct. 12, 2017 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (Nasdaq:AVXL) today announced pharmacokinetic (PK) and pharmacodynamic (PD) data for ANAVEX2-73 from its positive Phase 2a study in mild-to-moderate Alzheimer's disease patients. ANAVEX2-73 targets the sigma-1 receptor, which regulates neuroplasticity and cellular homeostasis. Anavex previously reported the Phase 2a trial successfully achieved both primary and secondary endpoints at the pre-specified 57-week analysis.
Data announced today establishes a clear concentration-effect relationship between ANAVEX2-73 and study measurements. These measures obtained from all patients during 57 weeks include cognitive and functional scores as well as a biomarker signal of brain activity. Additionally, ANAVEX2-73 activity appears to be enhanced by its active metabolite (ANAVEX19-144), which also targets the sigma-1 receptor with a half-life approximately twice as long as the parent molecule.
"I welcome such a thorough analysis of data before moving into a Phase 2/3. The intriguing ANAVEX2-73 data shown thus far exemplifies a precision medicine approach, to my knowledge, the first of its kind to broaden the scope of drug development in Alzheimer's disease and other central nervous system diseases," said George Perry, PhD, Dean of the College of Sciences at The University of Texas at San Antonio and editor-in-chief of the Journal of Alzheimer's Disease.
The Company is identifying the best responders to ANAVEX2-73 by using Ariana Pharma's KEM(R) advanced Artificial Intelligence technology. This cutting edge trial analysis will be used to more effectively design the upcoming Phase 2/3 clinical study, raising the odds of late stage trial success.
"We continue to be encouraged by the data from our Phase 2a clinical trial for ANAVEX2-73," said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. "We believe that through a systematic analysis of ANAVEX2-73 we might be able to increase the potential impact ANAVEX2-73 may have on this devastating condition."
On the conference call scheduled for this morning, Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex will be joined by Professor George Perry, PhD and Mohammad Afshar, MD, PhD, President and CEO of Ariana Pharma to discuss new findings from the ANAVEX2-73 Phase 2a trial. Further data will be presented at the Clinical Trials on Alzheimer's Disease (CTAD) meeting in November 2017.
Conference call and webcast information
Anavex will host a conference call at 8:30 a.m. ET today, October 12, 2017. The call will be webcast live at http://www.wsw.com/webcast/cc/avxl2 and slides are accessible through the investor relations section of the Company's website at www.anavex.com. To join the call live via telephone dial 1-866-866-1333 within the United States or 1-404-260-1421 from outside the United States. A replay of the call will also be available for a period of three months through the Company's website shortly after the call.
Absolutely right.
But but but, we still haven't seen an OLS fit! We are all doomed.
I think that is fair analysis of the situation.
While we await the trials to start and in turn yield hopefully positive outcomes, share price might move back up in $6 - 8 range once trials are underway.
In between, a potential licensing/partnership deal would move the share price higher. Will there be any such deal in the near term, that is the question...
If they can hold the share price above $2 for a while, then they might finally up-list to, I guess, Nasdaq.
Also the beer and sauerkraut is good.
Presumably there is a purpose to the Anavex Munich office.
Well the conference takes place in New York, and that's the truth!
I can't seem to find the post containing the petition link.
Maybe a sticky for it?
Yes, think about it!
Once AVXL has been revealed to desperately having mined meaningless data and using questionable statistical methods for a glimmer of efficacy, it would look silly to have your name on that petition.
Can I as none US citizen sign the partition?