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Pretty sad to be here at this level. Not much else to say about it.
Hope our chess master has a plan other than attend conferences.
I wonder what file as early as possible in 2024 means. Clear as mud.
I wonder what Kun’s probability of a successful filing is. Since it’s almost solely Missling’s decision to determine whether to try to file right away, wait for more data or do another trial.
I imagine that Kun’s input weighed heavily on the decision.
If it was, I think we have a good shot Chris, they would have filed immediately. They didn’t.
It was probably more like, it’s good, but if we get this and this, it will be better. And we eventually got what we needed. So here we are. Whether or not that includes some OLR data, I don’t know.
If it was, it’s not good enough or we have a small chance even if we get extra data, I think we would have seen all the data by now and plans to do another trial would be in the works.
Kun knows the data presented thus far is incomplete. They have “heat” on them already with the pending lawsuit. The truth will come out eventually. Obviously for now they’ve “fooled” the EMA into letting them proceed.
Do we/they really think all these inconsistencies pointed out will not come to light? Do we really think that maybe if they just try to proceed that maybe no one else will notice? I don’t think so.
Or do we think the data driven Chris Missling said, I don’t care, let’s move forward anyway. They’ll never catch us. Ha ha! Evil laugh. I’m guessing no.
So we’re in the dark a little longer and that’s ok cuz I’m pretty confident the smart people at Anavex aren’t trying to be middle school slick here.
Common sense tells me things are moving along nicely but slow as F
Although I agree with you, removing Missling at this time may do more harm than good.
Unfortunately we are stuck for the foreseeable future.
It’s difficult to play armchair CEO without knowing all the facts even though I’m often guilty of doing it.
Hope the peer review brings several, “oh now I get it” moments.
Peer review drop right before Needham.
Ha! Someone had to say it.
I’m gonna sue these mofos. Can’t let them get away with this.
Oh look honey they were actually sued before.
Let’s call them to see if we can get them to do it again since they’re familiar.
Ring ring. Ok. We know the recipe
Or it could be the short hedges. Either way it’s not fun and doesn’t change what we need to or can do about it.
At this point, even those of us trading to make a little extra coin are in a tough spot.
For now
It’s just a coincidence that all these events happened so close together. I don’t see any hidden agendas by any “secret cabal” trying to destroy our company.
Someone thinks they have a legitimate grip and is angry about losing money.
Peer review is sorely needed to increase morale and put to bed some silly assumptions.
Sad to have this lawsuit overhang in what arguable could be the most important time in our history.
Words matter and you can’t just blurt out whatever you want. Hope he’s learned that by now. I see this as just an annoyance in our path to success. Missling is a rule follower. I have no doubts that everything was done by the book. And if he needs to throw outa few Benjis to get rid of these pests, so be it.
It doesn’t take away from what we have. This little mini PR campaign if that’s what you want to call it may be a sign that the peer review is close. A little teaser if you will.
I don’t think it’s just one of his bright ideas that he thought of while playing battleship thinking it could make a difference to anyone.
Is Missling capable of any surprises?
We see the road ahead. The timelines are predictable with the ema and will be once it starts with the fda.
The peer review will shed light. I believe better than we expect. However, the predictability means no parabolic moves and an easily manipulated SP considering our low float.
Rett could be a surprise. Hopefully something else unexpected in the works.
It’s amazing how slow the peer review process is especially for small companies. Maybe AI can help speed up the process soon on all fronts of drug development.
It’s almost gonna be painful to hear Missling repeat himself at Needham.
I guess we’ll search for nuggets. Oh yeah. And hope some more.
How about some out-licensing? Missling spoke about that once many moons ago.
It’d be a good way to speed up the science, trials, revenue potential, etc.
I doubt the regulators will make the perfect an enemy of the good.
Especially when our good is already much better than the mediocre that was already approved.
Thanks. I would imagine that since it’s open label, the data at various time points have already been collected and crunched.
Why wait for the complete OLE when a 6 month view can give us a head to head comparison with Lecanamab and others?
I wonder if the 6 month will be part of the MAA. Waiting til July will delay a little more for no reason unless the 6 month was not as good as they thought.
When will the OLE be completed? TIA
Yep, a lot of good stuff happening. The Rett was an unexpected hiccup that we will muscle through. There’s a plan there and it will be revealed in time. Our rare disease franchise is too valuable and Rett gave us a lot to work with.
Everyone is shatting themselves with the silence and the low SP. Yep, it doesn’t feel good with no clear timelines. However an FDA nod to file will change everything.
We always say that Missling keeps things close to the vest. Before it was a little too close and I thought more transparency was needed. However, now at this moment, it may actually be wise to keep things close. We are in striking distance for a real seismic shift in how Alz and other CNS diseases are treated and viewed.
We have a solid platform with a boat load of Sigma one research backing our theories. We’re stepping on some big toes and we need to be selective on what we release and when.
We still don’t know what the peer review will reveal. If it does reveal some super responders as many here have speculated for some time then it might be better to make it a surprise. If QOL and other RWE measures are anything like we’ve seen the the 2a then watch out.
Patience and Perspective as one of our posters would often say. Steady?
Maybe that rebuke of the Alz Asoc in the Journal of Alz Disease is a precursor to the release of our peer review.
Timing is ripe with everything that’s happening in MAB and regulator land.
I’ll use Missling’s favorite word. Intriguing
It’s intriguing to see the lecanemab launch failure.
The slowing of brain atrophy is intriguing.
The very nice correlations between everything we have done is quite intriguing.
Missling pisses me off too but the unfolding events are intriguing to say the least.
It’s a gift for people getting in at this level. The Blank Check Preferreds help keep the vultures at bay.
I vividly remember that full page colored mailing about that vote. On nice card stock.
EMA. Uhm should we grant approval to this better, safer, cheaper, easily accessible drug that can given to ALL Alz patients while we face a huge economic burden that’s only getting worse with not many other available options is sight?
I vote no.
Ha!! Sure. That might happen in Bizzaro World but not on Earth.
Missling will bring this home and it will pay off handsomely despite his faults and past blunders.
I was referring to complete vs conditional MA. I thought Missling said they were going for “complete” MA through the centralized procedure, meaning we have more comprehensive data.
Did he? Can anyone confirm? Maybe I imagined it.
Complete Marketing Authorization (MA) and Conditional Marketing Authorization (CMA) are two different pathways for obtaining approval to market and sell medicinal products within the European Union (EU) and European Economic Area (EEA). Here's a comparison of the two:
1. **Complete Marketing Authorization (MA):**
- Process: Under the complete MA pathway, pharmaceutical companies submit comprehensive marketing authorization applications to regulatory authorities, such as the European Medicines Agency (EMA), for review and approval.
- Data Requirements: Companies are required to provide extensive data on the quality, safety, and efficacy of the medicinal product, including results from preclinical studies and clinical trials, manufacturing processes, and pharmacovigilance plans.
- Approval Criteria: The regulatory authority evaluates the application and assesses whether the medicinal product meets the necessary standards for safety, efficacy, and quality. If the criteria are met, the regulatory authority grants full marketing authorization, allowing the product to be marketed and sold in the EU/EEA.
- Conditions: Full marketing authorization is granted without specific conditions or obligations, although post-authorization surveillance and monitoring may be required.
2. **Conditional Marketing Authorization (CMA):**
- Process: Conditional marketing authorization is granted for medicinal products that address unmet medical needs and provide a significant benefit to patients, but for which comprehensive data are not yet available.
- Data Requirements: Companies must provide preliminary data on the quality, safety, and efficacy of the medicinal product, but additional confirmatory data may be required to support full approval.
- Approval Criteria: The regulatory authority evaluates the available data and assesses whether the benefit-risk balance justifies granting conditional marketing authorization. If the criteria are met, conditional marketing authorization is granted, allowing the product to be marketed and sold in the EU/EEA.
- Conditions: Conditional marketing authorization is granted with specific conditions or obligations, such as the requirement for the company to complete additional studies to confirm the product's efficacy and safety. Risk management measures and pharmacovigilance activities are also required to monitor the product's safety and effectiveness once it is on the market.
In summary, while both complete MA and conditional MA pathways allow medicinal products to be marketed and sold in the EU/EEA, they differ in terms of the data requirements, approval criteria, and conditions associated with marketing authorization. Conditional MA is intended for products that address unmet medical needs and provide a significant benefit to patients, but for which additional data are needed to support full approval.
The slow pace is agonizing.
One thing that’s for sure is we are not going away like many one trick pony companies with horrible balance sheets.
Thankfully our pipe is rich and our coffers are full with a low share count. We continue to attract new talent and are still moving forward as slow as it may seem.
Our science is real and continues to be explored, developed and hopefully partnered with to produce even better drugs/effects.
The SP has me sad and frustrated like everyone else here. I will let the story unfold knowing it’s gonna take much much longer than we want.
Any idea what items are being voted on in the next ASM? Hopefully we can send a clear message with our votes.
The FDA and EMA have similar views and processes on drug approvals. With our nod to move forward with a complete MA, it’s hard to believe the FDA would view our data so differently.
With two reg bodies giving us the go ahead, the SP should react accordingly. Missling would not go to the FDA if Kun said we are not ready. Kun’s view holds a lot of weight and most likely helps to drive Missling’s decisions.
The European Medicines Agency (EMA) may recommend a company pursue a complete marketing authorization (MA) rather than a conditional MA for several reasons, depending on the specific circumstances and characteristics of the medicinal product. Here are some potential reasons why the EMA might make such a recommendation:
1. Adequate Benefit-Risk Profile: The EMA may determine that the benefit-risk profile of the medicinal product is sufficiently well-established to support a full MA, without the need for additional data or conditions. This could be the case if the product has demonstrated significant clinical benefits with an acceptable safety profile in pivotal clinical trials.
2. Robust Clinical Data: The EMA may have reviewed comprehensive and robust clinical trial data demonstrating the efficacy, safety, and quality of the medicinal product, providing confidence in its overall benefit-risk assessment.
3. Unmet Medical Need: If the medicinal product addresses an unmet medical need or provides a significant therapeutic advance in treating a particular disease or condition, the EMA may prioritize granting a full MA to ensure timely access for patients.
4. Manufacturing and Quality Assurance: The EMA may assess that the manufacturing and quality control processes for the medicinal product meet the necessary standards for ensuring consistent quality and safety, supporting a full MA.
5. Public Health Considerations: In some cases, granting a full MA may be deemed more appropriate from a public health perspective, particularly if the product addresses a significant public health issue or if conditional approval could introduce uncertainty or risks for patients.
It's important to note that the decision to grant a full or conditional MA is based on a comprehensive evaluation of scientific data, regulatory criteria, and public health considerations by the EMA. The agency aims to make decisions that balance the need for timely access to medicines with the requirement for robust evidence of efficacy, safety, and quality.
If Missling is waiting for some OLE data to include in our package/meetings, how much is sufficient?
6 months? or maybe just long enough to compare with the mabs?
I think we’re almost at the point where the amyloid hypothesis becomes laughable.
Too much proof that shows it doesn’t work. Scientists soon or even now have no choice but to refute it. And the ones that still tout it will be ridiculed.
Even the Alz Association will need to pivot soon to something else as this time has become quite old. The problem is that big money donating BP have nothing else to fall back on.
No marching orders to start pumping this or that approach as the new idea because there not much to pump. Maybe they jump on removing tau bandwagon? Do they risk egg on their face by being g sideswiped with the sigma one? How foolish and behind will they look if Anavex sneaks by without them saying a word about it/us
The pivoting will need to happen or they risk losing face, money, influence, etc. Too much to lose by staying with the same horse. If not us and our science then who?
Once we file MAA, the SP should get a nice pop. It’s gonna be filed. Only way it doesn't is if our data is suspect and doesn't pass the smell test when the curtain is lifted.
Already passed the Kun test. No doubt he would have bolted if the data was suspect, if we didn’t follow sap or if the trial didn’t follow the acceptable protocols. I’m pretty confident they will be able to answer all questions satisfactorily.
No doubt Sabbagh and the gang of new hires have also seen, critiqued and verified.
Once filed, partners and smart money’s ears perk up. Hopefully before then we get some FDA guidance. Maybe in close proximity. 2 very big SP moving events. It will make this wait, pan, etc. worth it.
No, in gatekeeping procedures with two primary endpoints, each endpoint is typically assessed separately against a predetermined significance level, often set at 0.05. The requirement for statistical significance is applied to each endpoint individually, rather than their combined significance. If both primary endpoints individually meet the predefined significance level, they are considered statistically significant.
However, it's essential to consider the overall Type I error rate control when interpreting the results of multiple hypothesis tests. Gatekeeping procedures are designed to control the overall risk of making a Type I error across all hypothesis tests in the trial, including multiple endpoints. Therefore, the overall significance level is typically adjusted to maintain the desired overall Type I error rate, often using methods such as Bonferroni correction or hierarchical testing approaches.
In gatekeeping procedures, if one primary endpoint does not meet its predefined significance level, it's generally not appropriate to combine the other primary endpoint with the secondary endpoint in a statistical analysis. Each primary endpoint is typically evaluated independently to maintain the integrity and validity of the trial results.
However, if one primary endpoint does not achieve statistical significance, it may still be informative to explore the relationship between the other primary endpoint and the secondary endpoint in secondary analyses or exploratory investigations. These analyses could provide additional insights into the overall treatment effect or potential subgroup effects within the study population. However, such analyses should be interpreted with caution and considered exploratory rather than confirmatory.
In gatekeeping procedures, the combination of primary and secondary endpoints is generally not recommended for hypothesis testing if they were not predefined to be combined in the study protocol or statistical analysis plan. Each endpoint, whether primary or secondary, is typically evaluated independently based on its predefined significance level.
If one primary endpoint and one secondary endpoint individually meet their predefined significance levels (typically set at 0.05), they are considered statistically significant on their own merits. However, the decision to combine them for analysis should be carefully considered and justified based on scientific reasoning and prior planning in the study protocol or analysis plan.
Combining endpoints post hoc without prior justification can increase the risk of Type I error and compromise the validity of the study results.
“It's essential to adhere to the predefined analysis plan and statistical methodology to ensure the integrity and reliability of the findings.”
Serious question. Why would he say ADL met if not true? Others have stated that the 2 primaries, ADL and Cog need to add up to less than .05 and that each may have been under that threshold alone but when added together it wasn't.
I have not found anything that says that is a requirement. Anyone? And if the ADL was under .05, he definitely would have released it.
Missling - Oh crap, I really screwed up telling everyone ADL met. Why the F did I do that? Ok, I won't release the number and just wait for the peer review. Maybe if I stall long enough, I can get EMA approval before the real number comes out.
Then when it comes out, no one will care. If EMA doesn't approve, then I'm really F'd.
I've gotta believe Missling knows shareholder disappointment has reached an all time high. This is our first filing and it's a big one. He knows he needs to get it right. Not much news on the horizon, so we stay in limbo until further notice.
-Rett Guidance
-Peer Review
-FDA Alz Guidance
-MAA
That's all. Wait, complain, hope, wait, get angry, hope, wait, complain, etc.. Not much else to do or talk about.
Hopefully Missling will learn from this experience, grow and take us into the next chapter.
His learning curve is painful though.
It seems that our PDD data will/should be included in our MAA. The genetic data which has our patients returning to a more healthy state should be eye opening.
Our cumulative data is quite powerful and this current landscape makes it that much more appealing.
Yes, data from other relevant trials can be used to support a Marketing Authorization Application (MAA) submitted to the European Medicines Agency (EMA). These additional data can include results from previous clinical trials, pharmacovigilance data, real-world evidence, and other studies that provide relevant information about the safety, efficacy, and quality of the medicinal product.
When including data from other trials in an MAA, it's essential to ensure that the trials are adequately designed, conducted, and documented to meet the regulatory standards set by the EMA. The data should be relevant to the indication and patient population for which the marketing authorization is sought, and they should be appropriately analyzed and presented to support the application.
EMA evaluates all submitted data as part of the MAA review process to assess the benefit-risk profile of the medicinal product and determine whether it meets the necessary regulatory requirements for approval. Including data from other trials can provide additional evidence to support the overall assessment of the product's safety, efficacy, and quality.
There is no specific requirement for companies to list statistical methods in a Statistical Analysis Plan (SAP) from "best" to "worst." Instead, the selection and presentation of statistical methods in a SAP should be based on scientific principles, the objectives of the study, and the characteristics of the data collected in the clinical trial.
In general, the statistical methods outlined in a SAP should be selected based on their appropriateness for addressing the research questions and analyzing the data collected in the trial. The SAP should provide a clear rationale for the chosen methods and describe how they will be applied to achieve the study objectives.
While some statistical methods may be considered more appropriate or commonly used for certain types of analyses (e.g., regression analysis for examining associations between variables), the concept of ranking statistical methods from "best" to "worst" is not standard practice in clinical trial analysis.
Instead, the focus should be on selecting the most appropriate statistical methods to address the research objectives and ensure the validity and reliability of the study findings. It's also important for the SAP to provide transparency and detail regarding the planned statistical analyses to facilitate understanding, replication, and interpretation of the study results.
No mention of a hierarchy. From the bot at least. Maybe others have better sources.
As of my last update in January 2022, the European Medicines Agency (EMA) considers slowing of brain atrophy as a potential indicator of a drug's effectiveness against Alzheimer's disease, but it is not the sole criterion. When evaluating a drug for Alzheimer's treatment, the EMA assesses a range of factors including clinical outcomes, biomarker data, safety profile, and overall benefit-risk balance.
Slowing of brain atrophy can be an important biomarker in clinical trials, as it may indicate that the drug is affecting the underlying disease process. However, the ultimate goal is to demonstrate that the drug improves clinical outcomes such as cognition, function, or quality of life in patients with Alzheimer's.
The EMA evaluates all available data from clinical trials to determine whether a drug provides meaningful benefits to patients with Alzheimer's while considering the potential risks. If the evidence supports the drug's efficacy and safety, it may receive marketing authorization for use in treating Alzheimer's disease in the European Union.
FWIW Our AI friend says:
As of my last update in January 2022, the European Medicines Agency (EMA) recognizes brain atrophy as a relevant biomarker for Alzheimer's disease in the context of clinical trials and drug development. Brain atrophy, particularly in specific regions of the brain, can be indicative of neurodegenerative diseases like Alzheimer's. In clinical trials, changes in brain volume or structure measured through imaging techniques such as MRI can serve as important indicators of disease progression or response to treatment. However, the specific opinions or guidelines regarding brain atrophy as a biomarker for Alzheimer's may evolve over time as new research and evidence emerge. It's essential to consult the latest EMA guidelines or statements for the most up-to-date information.
Let’s see if they learned a lesson from the previous adcom fiasco.
I’m sure no one wants to resign. Maybe we’ll get another Kun Jin out of it.
Do you expect a PR tomorrow?
Need to get the Parkinson’s trial up and running, at least the imaging one that’s been talked about for some time.
PDD is on deck as well. Slow walking these trials does no one any good. There comes a time when you have to realize you need help. He’s stretched too thin already and has been for as long as I’ve been here.
Get that FN partner. Step on the FN gas with all that data you have.
Let go!!!!
Missling talks a big game with all these potentially addressable markets. How bout a little less talking and a lot more doing. Stop being a btch and get some damn help!!
Do not waste this year Just waiting, analyzing and filing. There’s a lot to do. Many indications to go for and a sht ton of people that need our drug.
Waiting and waiting is not savvy. It’s stupid. Get the right partner and go.
People go on Shark Tank to pour gas and what they have. Waiting for a deal until… that may never come is plain ole stupid.
I like how he emphasized that the genetic data showed our patients returning to a more similar state as the healthy non-alz population.
I think coverage is a possibility given the additional questions by the moderator/analyst.
To answer my own question. AI buddy says.
EMEA (European Medicines Agency) MAA (Marketing Authorization Application) filings can fail to get approved for various reasons:
1. **Insufficient Evidence**: If the submitted data doesn't adequately demonstrate the safety, efficacy, and quality of the drug, the application may be rejected.
2. **Safety Concerns**: If there are significant safety issues identified during the review process, such as unexpected side effects or risks outweighing benefits, the application may be denied.
3. **Efficacy Concerns**: If the drug's effectiveness is not proven to a satisfactory degree, the application may be rejected.
4. **Quality Issues**: If there are deficiencies in manufacturing processes or product quality, it could lead to rejection.
5. **Regulatory Compliance**: Failure to meet regulatory requirements, including documentation and labeling standards, can result in rejection.
6. **Incomplete Data**: Missing or incomplete data required for evaluation can lead to delays or rejection.
7. **Ethical or Legal Concerns**: Issues related to ethics, patient consent, or legal compliance can also result in rejection.
8. **Insufficient Benefit-Risk Profile**: If the benefits of the drug do not outweigh its risks, the application may be rejected.
Each case is unique, and the reasons for rejection can vary depending on the specific circumstances surrounding the drug and its application.
These percentages are not common knowledge to the average investor and institutional money knows they have time to get in. Getting the actual MAA filed will make that 85-95% more of a reality. That's when the smart money comes in.
FDA NDA percentages courtesy of our AI friend Chat GPT
The percentage of FDA NDA (New Drug Application) filings resulting in an approved drug varies from year to year, but historically it has been around 70-75%. However, this figure can fluctuate due to various factors such as the complexity of the drug, the quality of the data submitted, and evolving regulatory standards.
All this talk about percentages has me feeling pretty optimistic about our chances.
It’s pretty obvious that the high percentage of positive opinions due to the thorough examination of the data, trials, processes, etc. by CHMP allows them to weed out the “losers”. These crucial prior steps save them and the drug companies’ time.
Getting through this part seems to be the toughest hurdle that we have evidently passed.
I’m wondering about the reasons for the 5-15 percent failures. Any ideas/guesses as to why this relatively small group didn’t make it?
A closer look at data revealed issues, couldn’t handle the magnitude of the submission, misstep discovered in trial design? Any others?