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“Mitochondrial protection by the mixed muscarinic/sigma-1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Ab25–35 peptide-injected mice, a nontransgenic Alzheimer’s disease model”
Frontiers in Cellular Neuroscience, Volume 8, Article 463 (January 20, 2015)
Valentine Lahmy, Romain Long, Didier Morin, Vanessa Villard and Tangui Maurice
View Paper
http://www.anavex.com/publications/
Trial calendar derived from the post below -
PART A, 5 weeks - The last group of patients tested the week ending 10/17. Data presented 11/7.
PART B, 12 weeks - The last group of patients tested the week ending 1/9. Data could be released at any time.
PART B, 26 weeks - The last group of patients tested the week ending 4/16. Data might be released at this conference-
33rd Camerino-Cyprus Symposium
Event: Presentation by Christopher U. Missling, PhD, President and Chief Executive Officer
Date/Time: Tuesday, May 17, 2016 15:40 to 16:10
Location: Palazzo Ducale Piazza Cavour, Camerino, Italy
Miss Australia Tuesday, 01/19/16 05:55:02 PM
Re: Mikesc post# 50948
Post # of 59605
Well I would say it is imminent . My family member went through their tests on the 4/5th January and as I have said before, I am pretty sure they were in the last group to start the original trial. Wasn't there another medical conference coming up soon?
MabVax Therapeutics' Fully Human Antibody Approach to Cancer Therapeutics and Imaging Featured in Three Presentations at AACR Annual Meeting in New Orleans
PR NEWSWIRE 7:00 AM ET 4/18/2016
Symbol Last Price Change
MBVX 0.83up 0 (0%)
QUOTES AS OF 03:59:53 PM ET 04/15/2016
SAN DIEGO , April 18, 2016 /PRNewswire/ -- MabVax Therapeutics Holdings, Inc. , a clinical-stage immuno-oncology drug development company, announces that its fully human antibody approach to cancer therapeutics and imaging will be featured in three separate poster presentations at the American Association for Cancer Research (AACR) Annual Meeting currently underway in New Orleans.
"We are an innovator in using fully human antibodies to identify and combat cancer antigens that have historically proven difficult to target," said David Hansen, CEO of MabVax. "It is highly gratifying that our novel approach to harnessing the human immune system is being recognized in multiple presentations at the prestigious AACR Annual Meeting. We are currently in a Phase I trial with our lead candidate MVT-5873 as an immunotherapy for patients with metastatic pancreatic cancer. Preparations are also underway to begin a second Phase I trial in May, which will evaluate MVT-2163 as a next-generation PET imaging agent for the diagnosis and management of pancreatic cancer. We look forward to announcing preliminary data from both trials during the third quarter of this year."
An overview of the poster presentations at the AACR Annual Meeting are as follows:
"Phase I trial of HuMab-5B1 (MVT-5873), a novel monoclonal antibody targeting sLea, in patients with advanced pancreatic cancer and other CA19-9 positive malignancies" (O'Reilly, et al.) is being presented today by Paul Maffuid, Ph.D., MabVax's Executive Vice President of Research and Development. The poster provides an overview of the development and rationale for evaluating MabVax's HuMab-5B1 antibody in patients with the CA19-9 tumor biomarker that is expressed in approximately 90% of pancreatic cancers. As background for HuMab-5B1's clinical development, the poster covers antibody discovery, tissue binding selection, cytotoxicity profile, antitumor efficacy and pharmacokinetics. The poster features MabVax's Phase I development platform for evaluating HuMab-5B1, which includes the ongoing trial as a therapeutic antibody in patients with pancreatic cancer, as an immune-PET imaging agent with the trial slated to begin in May 2016, and as a radioimmunotherapy targeting pancreatic and other CA19-9 positive tumors, with that trial expected to commence in early 2017.
"Improving the efficacy of pretargeted radioimmunotherapy in preclinical murine models by utilizing bioorthogonal click chemistry" (Houghton, et al) is being presented by Jacob Houghton, Ph.D., Memorial Sloan-Kettering Cancer Center, on Tuesday, April 19. Pretargeted radioimmunotherapy employs the process of attaching a radioactive label to monoclonal antibodies after the antibodies have accumulated at the target site within the body. This allows for harnessing the power of monoclonal antibodies to deliver therapeutic radiation to cancer cells while limiting high radiation doses to healthy organs. Recently an innovative approach based on the use of a radioligand and modified monoclonal antibodies has yielded PET images with high contrast while delivering only a small fraction of the radiation dose produced by directly labeled monoclonal antibodies. This novel approach also overcomes intrinsic problems with past pretargeted radioimmunotherapy such as immunogenicity and noncovalent binding. Research in the poster evaluated leveraging this novel technology for the development of a safe and effective therapy. Single-dose therapy using this approach in studies in mice bearing human xenografts cancer showed marked reduction in size or complete elimination of the tumors, while reducing the effective absorbed dose of radiation. Studies to expedite clinical translation are currently underway.
"Novel fully human anti-GD2 monoclonal antibodies with potent therapeutic activity against neuroblastoma, sarcoma and melanoma" (Ragupahti, et al.) is being presented by Wolfgang Scholz, Ph.D., MabVax's Vice President of Antibody Discovery, on Wednesday, April 20. Gangliosides such as GD2, GD3 and GM2, are promising targets for antibody-mediated cancer therapy since they are expressed at high levels on the surface of several cancers, including neuroblastomas, sarcomas and melanomas. Monoclonal antibodies with anti-GD2 abilities have shown promising clinical outcomes in neuroblastoma and a chimeric anti-GD2 antibody was recently approved by FDA. However, murine-derived antibodies discovered so far show adverse effects that limit their clinical utility. The research presented in this poster evaluated the ability of two select fully human antibodies derived from immunized patients to overcome the limitations of murine-derived antibodies. The development candidates used in this research were derived from vaccinated, patient-produced antigen-specific antibodies with single and dual specificity for GD2 and GM2. These antibodies were shown to be very active in functional assays. Based on favorable in vitro and in vivo studies conducted in this research, the two selected fully human monoclonal antibodies merit further development efforts to evaluate potential utility for treatment of GD2-positive cancers.
About MabVax:
MabVax Therapeutics Holdings, Inc. (MBVX) is a clinical-stage biotechnology company focused on the development of vaccine and antibody-based products to address unmet medical needs in the treatment of cancer. MabVax has discovered a pipeline of human monoclonal antibody products based on the protective immune responses generated by patients who have been immunized against targeted cancers with the Company's proprietary vaccines. MabVax also has the exclusive license to the therapeutic vaccines from Memorial Sloan Kettering Cancer Center. MabVax has two cancer vaccines targeting recurrent sarcoma and ovarian cancer in proof-of-concept Phase II multicenter clinical trials. Additional information is available at www.mabvax.com.
Forward Looking Statements:
This press release contains "forward-looking statements" regarding matters that are not historical facts, including statements relating to presentations at the AACR Annual Meeting. We have no assurance that all of the product development pipeline will be fully developed by the Company. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "anticipates," "plans," "expects," "intends," "will," "potential," "hope" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon current expectations of the Company and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties. Detailed information regarding factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release relating to the Company may be found in the Company's periodic filings with the Securities and Exchange Commission, including the factors described in the section entitled "Risk Factors" in its annual report on Form 10-K for the fiscal year ended December 31, 2015, as amended and supplemented from time to time and the Company's Quarter Reports on Form 10-Q and other filings submitted by the Company to the SEC, copies of which may be obtained from the SEC's website at www.sec.gov. The parties do not undertake any obligation to update forward-looking statements contained in this press release.
Investor Contact:
Jody Cain, Senior Vice President
LHA
310-691-7100
jcain@LHAI.com
To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/mabvax-therapeutics-fully-human-antibody-approach-to-cancer-therapeutics-and-imaging-featured-in-three-presentations-at-aacr-annual-meeting-in-new-orleans-300252654.html
SOURCE MabVax Therapeutics Holdings, Inc.(MBVX)
Dr. Macfarlane is the director of Aged Psychiatry at Alfred Health. He has been running AD trials for 16 years. No connection to Anavex.
Professor Paul Maruff, Chief Scientific Officer of Cogstate. No connection to Anavex.
Not bad???
IMO, FUD doesn't hold up against statements from experts.
Macfarlane, trial investigator -
Five out of the 6 cogstate domains showed improvement, with 3 of these showing large effect sizes. The 'one-back' test within cogitate showed an effect size of 1.1 (meaning the standard distribution curve of the results was improved by 1.1 standard deviations, a huge effect size. A published meta-analysis of donepezil's benefit on the same test showed an effect size of 0.28. The significance of this particular change is underlined by the fact that 75% of our sample had already been taking a stable dose of donepezil for at least three months, so the improvements on the Cogitate battery (and on all the other cognitive outcome measures, were achieved over and above the gains our participants might already have achieved through being on donepezil. The same is true for the improvements noted on MMSE and ADCS-ADL, and the EEG markers (of which one ERP was statistically significant). I gather much is being made in certain circles that the remainder of the EEG markers, as well as the MMSE and ADCS-ADL scores failed to achieve statistical significance, but in a 5-week study of 32 patients it would almost have been beyond belief if this were to have been shown to be the case. The study was not powered to demonstrate significance, but the response on certain outcome measures was so marked that significance was achieved anyway (at a level of p=0.001 in the case of the Cogitate one-back task.
“While it is of prime importance to have confirmed that both the primary and secondary endpoints of the trial have been met, it is extremely encouraging to see the emergence of such strong cognitive signals after only 5 weeks of treatment. Such an outcome in a trial such as this is unprecedented in my experience, and the current results suggest that ANAVEX 2-73 could potentially make a significant difference in patients’ lives,” said Associate Professor Stephen Macfarlane, FRANZCP, Director of Aged Psychiatry at Alfred Health, who conducted the study. “We continue to receive extremely positive feedback about the effects of the drug from our study participants and their caregivers. The results justify a prospective comparison with current standard of care in a larger clinical trial.”
Other medical experts -
Professor Paul Maruff, Chief Scientific Officer of Cogstate commented: “The Cogstate tests measure people’s ability to store and use information. The results of the Phase 2a study demonstrate that ANAVEX 2-73 improves psychomotor function, attention and working memory. For attention and working memory these improvements were statistically significant with a p-value of p<0.05 and p<0.001, respectively and their magnitude clinically important. To my knowledge, we have not yet seen a drug that has improved quantitatively working memory to such an extent as seen with ANAVEX 2-73”.
Professor Harald Hampel, member of Anavex’s Scientific Advisory Board, and AXA Research Fund Chair at Sorbonne Universities’ Pierre and Marie Curie University (UPMC) in Paris, France, commented: “The collective data from this Phase 2a trial supports the concept of targeting the sigma-1 receptor with ANAVEX 2-73 with a degree of confidence that we did not foresee. Sigma-1 receptor presents an innovative interventional upstream approach to impact key cellular events believed to contribute to Alzheimer’s disease pathophysiology. The presented Phase 2a data underlines the importance of rigorously investigating a potential efficacy signal on co-primary outcomes such as cognition and function in larger and well-powered trials”.
To me, medical expert's statements out weigh FUD!!!
Any FDA designation that speeds the approval process and cuts costs is significant and should be described as such in the PR. Most companies realize this.
FDA Orphan Drug Designation is evaluated for drugs from all classes that are intended for the treatment of rare diseases, defined as diseases affecting fewer than 200,000 people in the United States. The designation provides sponsors with development and commercial incentives, including seven years of market exclusivity in the U.S., prioritized consultation by FDA on clinical studies and certain exemptions from or reductions in regulatory fees.
AVXL closed down a whopping .05 the day of the hit piece.
AF foolishly criticized Anavex for this statement -
“We believe that Orphan Drug Designation for ANAVEX 3-71 for the treatment of Frontotemporal dementia is a significant achievement,” said Kristina M. Capiak, Vice President of Regulatory Affairs at Anavex.
The market laughed at him. As a result, hopefully, he has lost some of his influence over AVXL.
A poster on another board looked up PRs from a few companies that received ODD -
“Receiving orphan drug status is significant”, stated Paul Gunn, President and CEO at Soricimed. “It is an important regulatory milestone, offering special incentives to Soricimed through the development stage of SOR-C13.”
“The FDA’s decision to grant orphan-drug status for Actimab-A is a significant milestone for the Company and recognizes the need for innovative new approaches to treat AML.
"Receiving U.S. Orphan Drug designation is another significant milestone as we continue to advance our pipeline of novel gene therapies to treat rare inherited eye disorders," said Sue Washer, President and CEO of AGTC.
"Orphan Drug Designation by the FDA for multiple myeloma is another significant milestone in the selinexor development program," commented Dr. Sharon Shacham, President and Chief Scientific Officer of Karyopharm.
"Receiving Orphan Drug Designation in the U.S. market for the development of our SBS therapy, NTRA-9620, to benefit SBS patients represents a significant milestone for Nutrinia," said Miki Olshansky, CEO, Nutrinia.
“Orphan drug designation from the FDA’s Office of Orphan Products Development is a significant milestone that will allow Ocugen to accelerate the clinical development of OCU100, which has the potential to be the first approved therapeutic for retinitis pigmentosa,” said Shankar Musunuri, PhD, MBA, founder and chairman of the Ocugen Board of Directors.
“The FDA’s decision to grant BerGenBio orphan drug status for BGB324 is a significant milestone for the company and recognizes the need for innovative new ways to treat AML,” Richard Godfrey, CEO, BerGenBio"
"The FDA orphan drug designation grant is an important regulatory milestone and marks a significant step forward in the clinical development of BPS-804."
ODD provides incentives during the trials as well as after approval. Even if 3-71 doesn't gain approval(heaven forbid), AVXL still benefits from the designation.
Significant -
The designation provides sponsors with development and commercial incentives, including seven years of market exclusivity in the U.S., prioritized consultation by FDA on clinical studies and certain exemptions from or reductions in regulatory fees.
ODD provides significant incentives.
Therefore, obtaining it is significant -
The designation provides sponsors with development and commercial incentives, including seven years of market exclusivity in the U.S., prioritized consultation by FDA on clinical studies and certain exemptions from or reductions in regulatory fees.
Yes, their drug is not a sigma-1 agonist.
Below is why that is bad. Notice the bolded by me. We heard about this in today's PR -
Anavex Encouraged by Data Showing Sigma-1 Receptor Reduces Tau Dysfunction, a Hallmark of Alzheimer’s Disease
New Report Validates Therapeutic Application of Anavex Compounds in Tau Diseases
NEW YORK, NY – May 21, 2015 – Anavex Life Sciences Corp. (“Anavex” or the “Company”) (OTCQX: AVXL), a clinical-stage biopharmaceutical company developing drug candidates to treat Alzheimer’s disease, other central nervous system (CNS) diseases, pain, and various types of cancer, is encouraged by recent data published in the Proceedings of the National Academy of Sciences. The research determines that activating the sigma-1 receptor with agonists can potentially reduce the devastating impact of tau dysfunction. Abnormal tau phosphorylation is a common characteristic in multiple neurodegenerative diseases. Alzheimer’s is the most widely recognized neurodegenerative disease associated with the aggregation of tau protein in the brain, with others including progressive supranuclear palsy (PSP) and frontotemporal dementia.
It has been previously reported that ANAVEX 2-73, targeting the sigma-1 receptor in a dose-dependent study, blocked tau and amyloid-beta (“amyloid”) proteins as well as memory deficits in a mouse model of Alzheimer’s disease. This data was published in the international scientific journal Neuropsychopharmacology. A reduction in these two main hallmarks of Alzheimer’s has the potential to stop, slow or reverse the disease. ANAVEX 2-73 is currently in a Phase 2a study for Alzheimer’s disease, and the Company expects to report preliminary data around the Q3 2015 timeframe.
“We are pleased to see further potential for our sigma-1 drug therapeutics, including ANAVEX 2-73, to prevent tau toxicity in Alzheimer’s and also possibly in other CNS diseases,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “Our team is excited by the findings of this publication and looks forward to the reporting of preliminary data for the Phase 2a Alzheimer’s trial later this year.”
The scientific paper, entitled “Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid,” is authored by S.Y. Tsai, T.-P. Su, et al., from the, National Institute on Drug Abuse, National Institutes of Health (NIH), US Department of Health and Human Services in Baltimore, MD.
http://www.anavex.com/?news=anavex-encouraged-by-data-showing-sigma-1-receptor-reduces-tau-dysfunction-a-hallmark-of-alzheimers-disease
One day. This is one of the best responses I have seen from IR -
In terms of the number of participants in the Phase 2a trial, this is because of the adaptive design of the trial (versus a trial that includes patients receiving a placebo). Here is a summary of comments made by Dr. Tasos Zografidis, the Vice President Clinical Operations of Anavex, and Dr. Christopher Missling, President and CEO, in a conference call earlier this year, which provides additional insight into the reasons Anavex is using an adaptive trial design.
+++++
TZ: For background information, there are two approaches in a clinical trial. One is the placebo controlled study. Here you have to estimate the number of patients needed if you are testing a hypothesis since you need a certain power; you need a certain number of patients. However, the methodology that we are using is very different, we just measure whatever effect is there. If you measure the effect and are able to reproduce it mathematically (mathematical modeling), then you can calculate the number of patients needed so as to see the effect. By using the adaptive trial methodology with population PK modeling, we are implementing mathematical modeling along with probability density function statistical methodology. That means that the results are looked at in confidence intervals. In the first approach you first estimate the number of patients and then you "see" the effect. In the second approach you first measure the effect and then you calculate the patients needed so as to truly "see" the effect. So, these are two opposite approaches with same outcome.
CM: We want to get a signal and the adaptive clinical trial allows us to increase the dose or decrease the dose until we see a signal. The mathematical model that Tasos speaks of sufficiently allows us to measure the data from these 32 patients because we are measuring many data points in this trial, from blood samples and the various cognitive tests, which allows for sufficiently precise data to learn how the drug works in order to select the number of patients needed for a Phase 3 pivotal trial. The number could range anywhere from 100 to 300 and the goal is to figure that number out.
The key is to understand the difference between a statistical standard trial, which is based on the placebo versus active dose in a number of patients, and the adaptive trial design statistical method used. The FDA has written a very eloquent guideline which you can find on the fda.gov website (http://www.fda.gov/downloads/Drugs/Guidances/ucm201790.pdf). The FDA states that with the adaptive trial design, which we are using, you need fewer patients, you are able to do this in a shorter period of time, you are more likely to demonstrate the effect of the drug, and you are getting more information on the treatment effect as well as a better understanding of dose response information in subgroups. Lastly, you are able to identify and optimize the parameters needed for Phase 3 effects. So, this Phase 2a trial is a very important stepping stone and building block for a successful Phase 3 trial. We want to avoid the same failure that the other Alzheimer drug trials experienced, and by implementing a different, innovative trial design for ANAVEX-73 in Alzheimer’s treatment, we are leading a more efficient study than a conventional study.
Amazing that the writer (called analyst by MF) highlights the accumulated deficit and leaves out AVXL's $13,800,000 in cash and their meager $600,000 per month burn rate.
( slide 33 ) http://www.anavex.com/files/Anavex_Presentation_Winter_2016.pdf
I suppose he could explain it better, but, he does say that each of the candles represents 30 minutes.
He uses a 30 minute chart. So, the 50 moving average is 50, 30 minute time periods.
Bravo!!!
Your #7 is a classic. I'm sure the medical professionals will enjoy it.
Everyday I see unjustified additional risk assigned to A2-73 based on flawed logic. Placebo effect is often touted as a negative by posters that fail to even mention A2-73's robust dose response curve.
I'm not an expert regarding the correlation of dose response curve and placebo effect and I don't know if Dr. Hooperg is either, but, he certainly has a strong opinion on it -
hooperg83 • Jan 11, 2016 7:15 AM Flag
Dose Response
A 5 week improvement of 2 points on the MMSE at approximately half maximum dosage is monumental. Dose dependence is a great indicator that the drug needs to saturate its ligands as expected, and thus very unlikely that this is placebo. Anavex is the real deal.
Melissa Davis, Feuerstein, and associated message board trolls, you lose.
Prana's drug was a good candidate for failure. It was not reversing the effects of Alzheimer's like A2-73, just possibly slowing progression.
Macfarlane's enthusiasm during the Prana trial was directed at one patient. Currently, his enthusiasm is for the entire A2-73 trial.
Macfarlane said that the drug seems to have slowed the progression of the disease by about 30 percent in patients with mild Alzheimer’s compared to placebo.
https://www.equities.com/news/prana-biotechnology-pran-continues-upward-on-alzheimer-s-disease-drug-news
The previous AD drug failures targeted the symptoms of AD rather than the causes.
“Our approach targets Alzheimer’s disease further upstream and apparently blocks these disease hallmarks, which may be a more promising approach. Combined with earlier findings that ANAVEX 2-73 restores mitochondrial functionality, this new report strengthens our compound’s potential in Alzheimer’s disease to also potentially act as a preventative drug.”
http://www.anavex.com/?post_type=news&p=1406
To be fair, almost 100% of the 99% of drugs that failed were directed at symptoms of Alzheimer's Disease, not the cause as is the case with A2-73.
Even the approved drugs target the symptoms and are near worthless.
Just knowing that data could come at anytime is good enough for me.
I'd like to see the pre-data rally take us to $6.00.
An experts view on placebo effect -
4. Of all the battery of tests which do you think most powerful for AD, and how did Anavex 2-73 perform in that test?
The One-back test (which measures working memory, a key domain of impairment in AD) within the Cogstate battery is the most difficult test, yet showed the greatest improvement. This outcome is unlikely to have been an artefact of any placebo effect...when placebo effects occur they are typically larger for the easier tests. In addition, whilst placebo effects are common with CNS sedative drugs, they are less likely to be present in tests of drugs used to enhance cognition...individuals cannot anticipate, or 'imagine' what a better score would consist of, and are unable to produce improved results through mere 'wishful thinking.'
This quote is from Dr. Macfarlane. He has been running Alzheimer's trials for 16 years.
http://seekingalpha.com/article/3672856-anavex-life-sciences-interview-dr-stephen-macfarlane
IR has already told us what to expect. I added the statement in red -
Pazzo1212 Thursday, 03/17/16 06:39:36 PM
Re: blu_1 post# 57177
Post # of 57652
Here's the email I received from IR yesterday:
Thank you for your email and support of Anavex Life Sciences Corp. (Nasdaq: AVXL).
In the AAT presentation (http://www.anavex.com/files/2016-03-12_AAT_Anavex_Presentation_2016.pdf), slide 24 demonstrates encouraging functional measurement of interim 12-week data, which was originally presented at CTAD. (Dr.Missling reported 12 week data before the end of the qtr)
Complete longitudinal data for the 12-week time point of PART B will be provided once this data becomes available. This is not yet available to the company. As stated in the third bullet point on slide 26 of the AAT presentation, please be assured that it will be issued once available, however we are unable to provide guidance on the timeline. The details relating to pharmacokinetics and pharmacodynamics are being fully analyzed so that there can be no doubt as to the cause-effect relationship of the 12-week efficacy data and this must be completed before it can be released.
The company is excited about the data received to date and by the request for an additional two-year extension from patients and caregivers, as announced in a press release March 10, 2016.
Please do not hesitate to contact our office if we can be of further assistance.
On behalf of Anavex Life Sciences Corp.,
Investor Relations
Toll Free (North America): 1 (866) 505-2895
Outside North America: +1 (416) 489 0092
Fax: +1 (416) 352 5239
ir@anavex.com
I doubt it, and think that is why both are required for approval.
It's going to be interesting to see how long it takes before major drug companies, with major bucks spent on AD (Lilly, Pfizer, Biogen, etc.), make their move for Anavex.
Eli Lilly ($LLY) didn't just surprise investors with its sudden about-face last week on its long-running Phase III program for the Alzheimer's drug solanezumab. Some investigators with years of experience in the field have been puzzling out the move to downgrade function from a co-primary to a secondary endpoint, even though daily function and improved cognition remain a required combined feature for any pivotal trial design approved by regulators on both sides of the Atlantic.
The bottom line is that Lilly clearly thinks its drug--which failed two earlier late-stage studies only to see Lilly double down, convinced that a second look at the data pointed to a clear clinical pathway that would lead it to one of the Holy Grails of drug research--is going to fail at significantly improving function. Facing the prospect of a repeat, high-wire flop for another one of its pricey home run swings, executives decided to retreat to cognition, hoping that the data would be good enough to argue the issue with regulators, who will be feeling the heat from patients and advocates with no truly effective therapies to turn to.
http://www.fiercebiotech.com/story/can-eli-lillys-regulatory-gambit-salvage-its-alzheimers-drug/2016-03-20
In addition to "the emergence of such strong cognitive signals", A2-73 recorded this on function -
In the interim analysis of the first 14 patients at week 12, the PART B portion of the study demonstrated a positive trend towards improvement over 12 weeks of ANAVEX 2-73 treatment on the secondary functional outcome measure, the Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory (ADCS-ADL) by +3.21 points.
http://www.anavex.com/?news=anavex-announces-positive-primary-and-secondary-endpoints-were-achieved-in-a-phase-2a-clinical-trial-of-anavex-2-73-in-alzheimers-disease%e2%80%8e
I picked some up today too.
Donepezil has been shown to work on less than 50% of patients.
Additionally, from July, 2015 -
Kanak Kanti De - Let me see if I understand the science correctly. Is the primary function of Anavex 2-73 to correctly fold back misfolded protein? By stimulating the sigma-1r chaperone? Is there anything else that it does?
Christopher Missling - Correct, however, additionally targeting Sigma-1 receptor and muscarinic receptors, which ANAVEX 2-73 does, is believed to increase cellular plasticity and reduce oxidative stress, inflammation, abeta generation and tau hyperphosphorylation (Note: Please see the publications section on Anavex's website and the following publication for protein misfolding.)
KKD - And adding Aricept to it - that is to reduce the plaque that's already been built up by existing misfolded protein, correct?
CM - Reducing the abeta plaque is also a function of sigma-1 R. Adding Aricept (donepezil) is believed to increase acetylcholine, a messenger for memory and hence work synergistically with ANAVEX 2-73.
KKD - So, A2-73 may work in early stages of the disease, when plaque buildup isn't considerable, but needs a plaque reducing agent in more advanced stages?
CM- Possibly, however, preclinically ANAVEX 2-73 might be sufficient to also reduce abeta by itself. Hence, could be applicable both in MCI and mild-to-moderate Alzheimer's disease. The current Phase 2a is in mild-to-moderate Alzheimer's disease.
KKD - However, since there's no biomarker to properly identify onset of Alzheimer's disease, A2-73 as a monotherapy doesn't work right now, and you need donepezil?
CM - That answer will come from this current Phase 2a. However, preclinical evidence shows ANAVEX 2-73 works very well alone and might have a further boost in combination with donepezil.
Technically, Dr. Missling already did report on 12 week data before the end of the quarter.
IR made sure they pointed this out in their email -
IR has already told us what to expect -
Pazzo1212 Thursday, 03/17/16 06:39:36 PM
Re: blu_1 post# 57177
Post # of 57652
Here's the email I received from IR yesterday:
Thank you for your email and support of Anavex Life Sciences Corp. (Nasdaq: AVXL).
In the AAT presentation (http://www.anavex.com/files/2016-03-12_AAT_Anavex_Presentation_2016.pdf), slide 24 demonstrates encouraging functional measurement of interim 12-week data, which was originally presented at CTAD.
Complete longitudinal data for the 12-week time point of PART B will be provided once this data becomes available. This is not yet available to the company. As stated in the third bullet point on slide 26 of the AAT presentation, please be assured that it will be issued once available, however we are unable to provide guidance on the timeline. The details relating to pharmacokinetics and pharmacodynamics are being fully analyzed so that there can be no doubt as to the cause-effect relationship of the 12-week efficacy data and this must be completed before it can be released.
The company is excited about the data received to date and by the request for an additional two-year extension from patients and caregivers, as announced in a press release March 10, 2016.
Please do not hesitate to contact our office if we can be of further assistance.
On behalf of Anavex Life Sciences Corp.,
Investor Relations
Toll Free (North America): 1 (866) 505-2895
Outside North America: +1 (416) 489 0092
Fax: +1 (416) 352 5239
ir@anavex.com
So many $billions have been spent, and wasted, on treating the symptoms of Alz.
On the other hand, A2-73 works upstream on the causes of ALZ -
Pre-clinical Study Demonstrates ANAVEX 2-73’s Ability to Preserve Mitochondrial Integrity and Block the Oxidative Stress and Cell Death that Leads to Amyloid-Beta Overproduction and Tau Hyperphosphorylation
“We provided clear evidence that the neuroprotective activity of sigma-1 receptor agonists, including the mixed muscarinic ligand/sigma-1 agonist ANAVEX 2-73, involves mitochondrial protection in AD models. Indeed, the drug efficiently protected mitochondria against amyloid-beta caused impairment of mitochondrial respiration, the key energy producing process within the cell,” said Tangui Maurice, PhD, one of the study authors and CNRS Research Director, Head of Team 2 ‘Endogenous Neuroprotection in Neurodegenerative Diseases’, at the University of Montpellier and INSERM. “Mitochondrial dysfunction and resulting oxidative stress are critical hallmarks of Alzheimer’s disease pathology and believed responsible for increased amyloid-beta production and Tau hyperphosphorylation.”
http://www.anavex.com/?news=anavex-2-73-could-prevent-alzheimers-disease-in-addition-to-modifying-and-treating-symptoms
Dane, there are some differences in the new 2 year trial. One notable difference is that donepezil is absent from the trial description.
Current trial -
The multicenter Phase 2a clinical trial of ANAVEX 2-73 consists of two parts and a total of 32 mild-to-moderate Alzheimer’s patients. PART A is a simple randomized, open-label, two-period, cross-over, adaptive trial lasting up to 36 days for each patient. PART B is an open-label extension for an additional 52 weeks.
The primary objective of the trial is to evaluate the maximum tolerated dose of ANAVEX 2-73. Secondary trial objectives include exploratory cognitive efficacy using mini-mental state examination score (MMSE), dose response, bioavailability, Cogstate and electroencephalographic (EEG) activity, including event-related potentials (EEG/ERP), as well as the relationship of ANAVEX 2-73 as an add-on therapy to donepezil (Aricept®).
New 2 year trial -
The new 104-week (two-year) extension of the multi-center Phase 2a clinical trial of ANAVEX 2-73 will follow patients with mild-to-moderate Alzheimer’s disease who have already completed 52 weeks in PART B of the study. Every three months, patients will be scheduled for physician visits to assess primary and secondary endpoints.
The primary endpoint of the new Phase 2a trial is to establish continued safety and tolerability of ANAVEX 2-73. Secondary endpoints are exploratory cognitive as well as functional measures using Mini Mental State Examination (MMSE) and evaluation of Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory (ADCS-ADL), respectively.
PD (pharmacodynamics) = what a drug does to the body
Dose response is an example of this. The five week data on 11/9 didn't include this.
PK (pharmacokinetics) = what the body does to a drug
Includes absorption, distribution, metabolism, and elimination. Half life is an example of this. This wasn't included in the 11/9, five week data.
http://www.themednote.com/2011/07/10/pharmacodynamics-vs-pharmacokinetics/#.Vuvq4Y-cHIU
Thanks for sharing the info!
I have been expecting 12 week top line data and 5 week PK/PD data.
It looks like we're getting complete 12 week data.
I'm really looking forward to this.
"Should be ready" is a lot different than "we all know the 12 week results are available now and could be revealed".
I'm pretty sure there is an outside lab involved. They must have promised results before the end of the qtr. As of March 10th, Dr. Missling didn't have everything.