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Joseph...out of respect for Annelise and her family's privacy, I think you should remove the link.
Thanks
Any idea how long ago they posted that message on FB?
Thanks
When Anavex submits the NDA for Rett, the FDA requires them to submit all of the data related to A2-73...so they will most likely submit the OLE data using the ~350 patients...rather than wait for the completion at the end of July, 2024.
Side note: If Anavex has had this information for some time, I would think the TGD is privy to the results...and thus, it could be another reason why Dr. Missling chose to buy the 320,000 shares of AVXL when he exercised his options.
(I'm pretty sure this doesn't violate FCC insider rules because TGD was forced to exercise his options before they expired...but maybe SAB or boi can enlighten us?)
Yup. Thanks
Mr. Palmer...I think he said that he was going to aggressively approach the FDA...which is much different than claiming that he was going to pursue the FDA for Accelerated Approval.
And remember, Dr. Jun Kin came aboard in early January and has undoubtedly made several recommendations to TGD that will increase our chances of getting FDA approval.
Perhaps Dr. Jun Kin told Dr. Missling to wait for the OLE before approaching the FDA. Or...Perhaps Dr. Jun Kin told Dr. Missling to wait for FDA approval for Rett...and then repurpose the drug for Alzheimer's Disease. (Which was the original game plan anyway, IMO)
One other thing to remember, TGD told everyone at the ASM that we will enjoy seeing the P2b/3 data once it is presented in the 2H of 2023. (paraphrasing)
The next 3 - 4 months should be very exciting for those of us that have the patience to wait.
Scratch that request.
Notice he said that AVXL is his top holding within his portfolio.
Some encouraging news after the Maui fire
Quote: "This is likely music to the ears of someone like Emil Kakkis, M.D., Ph.D., CEO of Ultragenyx, who’s long been advocating for expanding the use of accelerated approval for rare disease patients. Core to his argument, described in a previous interview with Fierce Pharma, is that if the FDA leaned into surrogate endpoints for rare disease patients, then the development process would hasten and there’d be a more viable commercial landscape."
Another quote: The FDA doesn’t “have to get to 100% certainty between an accelerated approval endpoint and a clinical endpoint," Marks added.
“If that were the case, there wouldn't be a difference, then we wouldn't have accelerated approval,” he said. The agency can mitigate uncertainty by “using science to the fullest extent," according to Marks—be it available animal data or strong human biomarkers related to, for example, the expression of a particular protein."
"Though we're still in early days here and I think we'll see some refinements, and I think we don't want to be overly dogmatic with this, I think it's overall an advance," said Marks.
This is a great article. Thanks bb8675309
Thanks Joseph.
Can someone post the entire article?
I already receive too many emails from other companies.
Thanks
Great post falconer. It's always nice to read your background every now and again.
We have a lot of great members that contribute to this board...and I especially appreciate your posts.
abe
Have you started buying back in yet, Raja?
If not, I think you might want to start buying now because the price could jump into the $20s if Anavex releases really good Rett results...or AD publication.
Good question. If it is a one and done, then it comes down to cost and long term effectiveness.
Let's hope their treatment is safe long term. I think Serepta just barely received FDA approval with a vote of 6-5
Serepta's gene therapy costs $3.2 Million per patient...so I'm wondering what Tasha is going to charge?
Going to be hard to compete with A2-73...even at the initial cost of $500k/year.
You have to have a market that will pay for your drug before you can make any money...and there's not too many people that can afford $3.2 Million for treatment!
Some of the issues highlighted in the article below.
https://www.investors.com/news/technology/srpt-stock-halted-sarepta-wins-fda-approval-for-duchenne-gene-therapy/?src=A00220
It's not a matter of you granting the definition to me...it is the procedure that is used for repurposing a drug. Plain and simple.
If you've finally seen the light on this subject, good.
Yes it most certainly is.
Once A2-73 has obtained FDA approval for Rett, that is the disease the FDA has assigned to that drug.
Therefore, if Anavex plans to submit an NDA using A2-73 for Fragile X (or any other disease) without conducting a P1 or P2, then they are in fact repurposing that drug.
Excellent post Schmiggins. Thanks for your DD.
"The key consideration is scientifically and medically supporting the change in the repurposed drug product by relying on the original drug’s approval data and then “bridging” that data to the repurposed drug under the new conditions of use. Although bridging studies may take the form of pharmacokinetic or bioequivalence studies, in many cases FDA will require the completion of at least one clinical trial to support approval of the repurposed drug. Understanding the nature and impact of the product changes — and what supporting data the FDA will need to see — is therefore critical to receiving approval for a repurposed drug."
https://www.clinicalleader.com/doc/how-to-navigate-drug-repurposing-and-bridging-studies-0001
I guess I missed that point...as did Investor2014.
However, it doesn't change the fact that that was an independent company with their own guidelines for repurposing a drug.
I asked for specific FDA guidelines.
I wholeheartedly disagree.
Once A2-73 is approved for Rett, Anavex will be conducting numerous P3 trials for other rare diseases...especially Fragile X. If the P3 trial for Fragile X is successful, Anavex will most certainly repurpose A2-73 and submit an NDA - immediately!
The same scenario will be executed for Alzheimer's Disease if the FDA agrees that our n=509 P2b/3 and the OLE (along with all of the other P1 and P2 results) are a large enough package to qualify for a drug repurposing NDA.
IMO, this has always been the game plan that Dr. Missling was going to execute.
One thing is for sure, Anavex has filed dozens of patents for neurological diseases that A2-73 can be used for...and I guarantee that our pipeline is going to explode once A2-73 is approved for Rett.
Just sit back and enjoy the ride folks. The second half of 2023 is just the beginning of a long line of successes that we'll experience.
Cheers.
Are you saying that it is unrealistic for Anavex to repurpose A2-73 once it is approved for Rett?
Here is your other post where you changed your tune and now say that a P2 can be skipped.
Investor2014
Re: abew4me post# 427151
Sunday, August 13, 2023
Post# of 427159
Indeed as I said the P1 trial can be skipped when repurposing an already approved drug. As I also said, in some (limited) cases a P2 trial may be skipped or as Anavex likes to do run a P2/3 trial and see if it sticks.
[Note: You never said that it can be "skipped" in your original post. You changed your tune once I showed you that it can in the article you posted.]
This is your original post...and it specifically states that a P2 is "required". Of course, once I showed you that it can be skipped, you changed your tune.
Investor2014
Re: abew4me post# 427132
Sunday, August 13, 2023
Post# of 427158
Repurposing a drug generally refers to discovering that it may have benefits for some indication(s) not originally intended. Of course that would cut out some development time and testing in human P1 trials, but still required at least the P2 and P3 clinical trials per usual to prove that thesis.
Hmm...thought you said that a P2 is "required". Good to see that you agree that it can be skipped.
In any event, I'm most interested in FDA regulations. If you come across any regs for drug repurposing, please post on this board.
Thanks
That chart has nothing to do with FDA regs. It is showing an independent study for EB and how they are approaching a repurposed drug.
Furthermore, after reading the article, it states the following:
Initially a trial may only be carried out on a small number of people in case there are unforeseen side effects. If a phase 1 trial shows a new treatment is safe, it can be trialled on people with symptoms in a phase 2 trial. This stage can be skipped if a treatment already in use for another condition is being considered as it will already have been shown to be safe to use. This is called drug repurposing and is an important part of our research strategy as it has the potential to provide effective treatments more quickly to families living with EB.
I think Doc328 would disagree with you that repurposed drugs are "required at least the P2 and P3 clinical trials per usual to prove that thesis".
Can you show any FDA regs that require a P2 trial for repurposed drugs?
The NIH is currently running a large P3 trial with a basket full of FDA approved drugs to see if they can repurpose those drugs...no mention of a P2. (See below)
NIH funds large Phase 3 clinical trial to test repurposed drugs for treating COVID-19 symptoms
Using an ACTIV master protocol, the trial will focus on potential interventions for mild-to-moderate illness.
The National Institutes of Health will fund a large, randomized, placebo controlled Phase 3 clinical trial to test several existing prescription and over-the-counter medications for people to self-administer to treat symptoms of COVID-19. Part of the Accelerating COVID 19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership, the ACTIV-6 trial aims to provide evidence-based treatment options for the majority of adult patients with COVID-19 who have mild-to-moderate symptoms and are not sick enough to be hospitalized. NIH will provide an initial investment of $155 million in funding for the trial.
Several drugs currently are recommended for the treatment of hospitalized patients with moderate to severe COVID-19, including the antiviral drug remdesivir, the anti-inflammatory baricitinib, and corticosteroids. Additionally, the U.S. Food and Drug Administration authorized emergency use of intravenous monoclonal antibodies in non-hospitalized patients with mild to moderate COVID-19 who are at high risk for severe disease. However, medications that can be self-administered at home to reduce COVID-19 symptoms are critically needed.
The ACTIV-6 protocol will explore a pool of up to seven drugs approved by FDA for other conditions - an approach called drug repurposing - and test their safety and effectiveness in treating mild to moderate COVID-19. Because the drugs under consideration already have been tested in humans, repurposing could deliver COVID-19 treatment options sooner. Drugs will be administered orally or by inhaler and will be easy for participants to take at home. Participants will be assigned randomly to receive either a placebo or one of the treatments, which will be sent to them by mail.
Enrollment is expected to open in a few weeks to up to 13,500 participants who are at least 30 years old, have tested positive for SARS-CoV-2 infection and have experienced two or more mild-to-moderate symptoms of COVID-19 for no more than seven days. Researchers plan to assess changes in patients' symptoms over a 14-day period, as well as hospitalizations and deaths over a 28-day period. They also will assess long-term COVID-19-related symptoms at 90 days after treatment begins. The list of drugs that will be added to the study arms is still being finalized. All the drugs will have established safety records and early indications from smaller or less controlled studies of effectiveness against COVID-19.
The trial will focus on enrollment of people within minority, rural and other communities that are significantly affected by COVID-19 but lack access to major academic medical centers, where large clinical trials usually take place.
With funding provided by the American Rescue Plan Act, NIH's National Center for Advancing Translational Sciences (NCATS) will oversee the trial. The Duke Clinical Research Institute, Durham, North Carolina, an NCATS-funded Clinical and Translational Science Awards (CTSA) Program hub, will serve as the clinical coordinating center, and the Vanderbilt Institute for Clinical and Translational Research CTSA Program hub at Vanderbilt University Medical Center, Nashville, Tennessee, will serve as the trial's data coordinating center.
To expedite enrollment in ACTIV-6, NCATS and its Duke-Vanderbilt Trial Innovation Center will partner with the Patient-Centered Outcomes Research Institute (PCORI), an independent nonprofit research funding organization. PCORnet, the National Patient-Centered Clinical Research Network, which is funded by PCORI, will support the ACTIV-6 governance and operations. In addition, PCORnet sites will enroll participants from a broad range of communities.
"Getting approval for a new drug to come to market usually takes years," said Joni Rutter, Ph.D., NCATS acting director. "By leveraging drug repurposing and existing national clinical trial networks, ACTIV-6 aims to speed the delivery of definitive answers about available drugs that could help people manage COVID-19 symptoms at home."
https://www.news-medical.net/news/20210420/NIH-funds-large-Phase-3-clinical-trial-to-test-repurposed-drugs-for-treating-COVID-19-symptoms.aspx
Schmiggins...I agree that 3-71 is fully safe. See results below
ANAVEX 3-71 Meets Primary, Secondary End Points in Phase 1 Study
Jan 12, 2022 Abby Reinhard
A phase 1 study of ANAVEX 3-71 (NCT04442945), an oral small molecule agonist of both SIGMAR1 and CHRM1 (Cholinergic Receptor Muscarinic M1), met its primary safety end point, as well as its secondary end point, Anavex Life Sciences recently announced. The drug is in development for treatment of neurodegenerative diseases and has previously been granted orphan drug designation by the FDA for treatment of frontotemporal dementia (FTD).1
The double-blind, randomized, placebo-controlled trial evaluated the safety, efficacy, and pharmacokinetics (PK) of oral escalating doses of ANAVEX 3-71 in evaluating in healthy patients. Investigators concluded that the treatment, previously known as AF710B, was well tolerated in all cohorts receiving single doses, ranging from 5-200 mg daily. No serious adverse events or significant lab abnormalities were reported. The treatment showed linear PK, which was also dose proportional up to 160 mg and was unaffected by gender. Food was not found to have an effect the bioavailability of the treatment.
“We are pleased with the phase 1 trial results for ANAVEX 3-71 and are eager to advance ANAVEX 3-71 into phase 2,” Christopher U. Missling, PhD, president and CEO, Anavex, said in a statement.1 “These encouraging results provide a proof of concept of our SIGMAR1 product platform and helps validate Anavex’s approach to CNS target selection and drug discovery and increases Anavex’s confidence in the potential of our precision medicine technology to address serious neurodegenerative diseases.”
Meeting its secondary end point, the study also characterized the effect of ANAVEX 3-71 on electrocardiogram parameters, which were not clinically significant in any subject. Across all dose groups, participant QT interval corrected for heart rate by Fredericia’s cube root formula measures were normal, with no differences observed between treatment and placebo groups.
The study included a total of 42 men and women between the age of 18-35 years who were given up to 4 single escalating doses of ANAVEX 3-71 or placebo, administered orally over a 30-day period. Participants were divided into 3 cohorts, the first receiving 5-50 mg oral doses of ANAVEX 3-71, the second receiving 55-200 mg, and the third receiving placebo. Participants were required to be non-smokers, have a body mass index of 19-28 kg/m2, have a body weight of 60-120 kg, and be in generally good health at the time of screening. Women were required to be of non-childbearing potential or using contraception.
Based on the positive topline results from phase 1, Anavex plans to evaluate the treatment in a biomarker-driven clinical development dementia program for the treatment of FTD, as well as schizophrenias and Alzheimer disease. The study will be a quasi-basket trial and is anticipated to being in 2022 and will evaluate longitudinal effects of the treatment.
“In addition to biomarkers…we would like to look at the neurofilament light change, NFL,” Edward Hammond, MD, MPH, PhD, chief medical officer, Avanex Life Sciences, said during a webcast conference call discussing the topline results.2 “We will also look at plasma and serum concentrations of glutamate and other related amino acids. We are looking at TDP43, GRP78 concentrations as well, so it is quite a comprehensive biomarker strategy that will be able to demonstrate the effect of 3-71 on these pathologies, in order to give confidence going into further development.”
REFERENCES
1. Anavex Life Sciences reports positive results from phase 1 clinical trial. Avanex Life Sciences. January 10, 2022. Accessed January 11, 2022. https://www.anavex.com/post/anavex-life-sciences-reports-positive-results-from-phase-1-clinical-trial-of-anavex-3-71
2. Anavex 3-71 Phase 1 Top Line Data Conference Call. Anavex website. January 10, 2022. Accessed January 11, 2022. https://www.anavex.com/anavex3-71phase1toplinedataconferencecall
https://www.neurologylive.com/view/anavex-3-71-meets-primary-secondary-end-points-phase-1-study
Steady...thanks for the PM.
I couldn't find any regs either...which is pretty strange because repurposing a drug is pretty common nowadays. And it has been widely used for Covid-19 https://www.news-medical.net/news/20210420/NIH-funds-large-Phase-3-clinical-trial-to-test-repurposed-drugs-for-treating-COVID-19-symptoms.aspx
Maybe Doc328 can find some regs on repurposing a drug since he was the first one to bring up the subject.
BTW...I stopped my premium membership a few months ago; so I can't respond privately anymore.
I wish I could take credit for this plan, but I'm pretty sure Anavex has been preparing for this scenario from the start. (Had it not been for the Covid virus, we would've already had A2-73 approved for Rett)
Repurposing a drug and applying towards the NDA has been discussed on this board several years ago...and I believe Doc was the first to mention it. (Gotta give credit where credit is due!)
Don't have the BTIG link but I do have the recording for our quarterly financials...that includes a pretty good Q & A!
https://www.anavex.com/copy-of-2022-first-quarter-financial
Getting ready to break 2 Million shares.
The FDA doesn't have any disqualifications of repurposing a drug simply because it was approved under orphan drug designation...because they require the applicant to run a separate Phase 3 trial to prove its efficacy (and safety) with patients that are suffering from the disease they are requesting approval for.
Hope that makes sense.
Although I have done a lot of DD, I should also add that all of my comments are my own opinion and should not be used to buy or sell stock of AVXL or any other symbol.
Yes. I think they'll present the OLE as an alternative to a full-blown confirmatory trial because their NDA (New Drug Application) will be focused on repurposing A2-73.
This has been Anavex's plan from the beginning (IMO)...but the Covid virus delayed the approval of Rett. Now everything is back on track. (See my earlier post below)
****************************************************************************************************
Once A2-73 is approved for Rett, Anavex can repurpose the drug for Alzheimer's Disease...which will expedite the approval process. (See explanation below)
Drug repurposing, or repositioning, is a strategy aimed at identifying new uses for already approved drugs, which fall outside their original medical indication. This strategy has led not only to the successful preclinical and clinical testing in multiple neurological disorders, but also to the reevaluation of disused drugs, epitomized by the remarkable case of thalidomide.
In recent years drug repurposing has covered a wide range of neurological disorders, from neurodegenerative and neuropsychiatric to drug abuse-related disorders.
Alzheimer’s disease and Parkinson's disease, for example, are the two most common neurodegenerative diseases, for which only symptomatic therapies are available, while neuroprotective drugs are still an urgent unmet need. They are therefore in the top list of neurological disorders for the investigation of repurposed drugs, targeting both the disease neuropathology and symptoms.
**************************************************************************************************
The FDA can approve an NDA (New Drug Application) with one successful P3 trial and the repurposing of an FDA-approved drug.
So, if the FDA approves A2-73 for Rett, that would qualify for the first half of our Alzheimer's application. The other half would be our P2b/3 AD trial.
IMO, this is the main reason why Anavex wants the FDA to approve Rett first. Once it is approved, they can expedite the entire process for our Alzheimer's application by simply repurposing A2-73. (Qualifying for the $100M voucher is a bonus)
Our FDA guys know what they're doing...especially Dr. Jin.
TGD and his team know what they're doing. Just sit back and enjoy the ride.
We've been oversold for quite awhile...so I'm glad we're breaking away from the XBI.
Let's hope the broader market doesn't throw water on our momentum.
Volume just broke 1 Million shares. That's a very big deal for this little biotech stock.
Quote: Nice to be well up on the reloads... thanks!
You can say that again!
Heavy Volume. Just broke 500,000 shares traded
I think they had all of the data...they just didn't have the ability to get everything fully analyzed. And that would also explain why they had to take down all of the posters after CTAD.
IMO, of course.
The last CRO didn't even give his data to Anavex until December 4th...so I don't think you can honestly claim that Anavex has had all of their data for one full year.
And as I recall, Anavex reported just two months ago that they "recently received data" that showed surrogate biomarkers that would allow them to apply for AA.
So things may be progressing at a snails pace, but the quality of the data will be second to none...especially with Dr. Kun Jin on board.
I think Sumit Roy is spot on.
Our share price is going to continue to follow the XBI (up or down) until A2-73 is approved for a disease...which I expect next year.
We should get a good bump when the TLR is announced for the EXCELLENCE Rett trial...which is due sometime in the next 3 - 4 months. After that, we should get some spikes in our SP along the way...but the BIG payoff is still 12 - 16 months away.
Just my opinion, of course.