From: Erica Santoni [mailto:esantoni@accelclinical.com]
Sent: Wednesday, April 5, 2023 11:24 AM
To: Marc Anderson
Subject: Screening on pause
Good morning,
I received an email late last night, that Sponsor has decided to pause all Screening activities effective immediately. They have had an increase in patients and not enough study drug now, supply and demand.
I apologize for the inconvenience as soon as they open Screening I will notify you and get you scheduled.
Kind Regards,
Well that stinks. I had received an email a few months earlier that they would be expanding sites closer to my Chicagoland area.
Really. I was screened yesterday, but don't know if they'll go forward with me.
Seems pretty bad to launch a trial for 450 people then find out you don't have enough drug
I hope thats not the case. If I hear anything regarding me last email I will let you know.
I thought your PTT would exclude you.
I was afraid it would, too, but not so - far.
it means that your PTT FUS effect is gone? Why do you need this trial?
The PTT benefits are still in place. The PTT didn't resolve everything. I didn't expect it to. I still am progressing. Gait, speech, GI issues, etc.
so it means the benefits are not in place, if your gait and speech worsening neans that you had the benefits only for a couple of years, wow I had high hopes for this procedure.😥😥😥😥😥
Can you please tell me what benefits did you have and what percentage of the benefits are still there
"...so it means the benefits are not in place..." I consider all the benefits still in place.
I don’t know that your expectation that PTT (claims to) resolve gait and speech is correct.
Where did you read that?
The procedure completely resolved tremors, dystonia, rigidity, and mostly resolved bradykinesia and back pain.
I have several posts regarding the procedure under my profile.
I wouldn't rely on one person's experience to make such a momentous decision.
thank you
I will try to find and read your posts.
So can I conclude that the relief in bradykinesia, tremor and dystonia you got is holding 90% and not fading🙏🙏🙏🙏🙏🙏🙏🙏
yes
other good information is at "Focused ultrasound for Parkinson's disease" on Facebook
Will it be 4x per day dosing, Marc?
Art
1/day
Having enough drug to cover the number of participants is so fundamental, it raises questions about their explanation.
It could be a packaging problem...hard to know
Unexpected supply chain issue?
could be but after reading many of the other posts on this chain I am leaning towards lackluster results from the interim analysis and cash flow problems...
That just sounds SOOO unlikely. I could believe it of zhittya genesis, but Annovis? Really. The trial launched on the basis that depending on the early results they might need to expand significantly, and they announced they would be launching trials in EuropeAnd they ran out of pills? 🤔🙄
Shortly after analysing those preliminary results and issuing a press release that damns with faint praise they run out of pills!
I suppose maybe
Anything to do with the concurrent study using it with AD? Maybe overstretched resources. Very disappointing.
450 people in the trial. Two thirds of them get the real drug for six months. 300×180 = 54,000. 27,000 doses of 10 mg & 27,000 doses of 20 mg
How hard can that be?
Maybe they ran out of placebo ☹️
I don't think the entire trial has been put on hold or, as a participant, I would hope they would have notified me. HOWEVER, I have reasons to be very disappointed.
1. In the Phase 2 trial, UPDRS improvements were supposedly realized after just 25 days. I am in my fourth month in the Phase 3 trial and have not noticed any improvements other than perhaps improved memory, but that is subjective and could be placebo effect.
2. I have been in contact with at least three other trial participants on this site. I will gladly be corrected on this, but I don't think any of us have noticed any dramatic improvements.
3. Annovis Bio recently gave an interim report which was allegedly related to whether or not they needed to increase the number of trial participants. They didn't publicize it much, but they concluded that an increased sample size was not necessary. That lead me to believe either (1) They were having obvious success so additional participants were unnecessary or (2) They were obviously failing and having more participants was pointless and expensive.
The email to Marc with such a flimsy explanation, plus the factors set forth above, lead me to conclude that Buntanetap is not our silver bullet and I have wasted time and money flying or driving to Kansas City each month since December.
Dang.
I’m starting to wonder too. Anavex 2-73 is next thing I’m pinning my hopes on if this doesn’t work. I think of this condition as being analogous to a selection test for the special forces - an exhausting, increasingly hard, slog between mountains with the aim of being selected for a new lease of life. (This is my way of coping anyway.)
Jim,
What you said in #2 concerns me because the odds of all 4 of you getting the placebo are tiny. (Can any of you math wizards figure what those are?)
Marc
PS They only stopped screening (for new participants,) so those who are in will continue.
Why didn't you choose Milwaukee?
My son lives in Des Moines, which is enroute to Kansas City and Kansas City is only two hours further away from me than Milwaukee.
.33*.33*.33*.33 = 1.19%
I think that is right.
Move the decimal. How about 0.01185921? 33% X 33% X 33% X33%?
It is the same value. 1.2%
I think. I got your number too, but then I did it in Excel and clicked on percentage for format.
I was just notified I have my baseline visit 4/26
The more I think about it, the more I realize their explanation is BS.
I think Annovis Bio is having a difficult time financially. I think that may have something to do with their hesitation with increasing the number of cohorts in this trial.
Financial Results for the Fourth Quarter of 2022
Cash and cash equivalents were $28.4 million as of December 31, 2022. Research and development expenses for the quarter ended December 31, 2022 were $6.2 million, compared to $2.9 million for the same period in 2021. The increase was primarily the result of an increase of $4.3 million in clinical expenses, as the Company incurred costs related to its Phase 3 study in early PD patients and its Phase 2/3 Alzheimer's study, partially offset by a decrease of $1.0 million in stock-based compensation expense. General and administrative expenses for the quarter ended December 31, 2022 were $1.6 million, compared to $3.0 million for the same period in 2021. The decrease was primarily the result of a decrease of $1.5 million in stock-based compensation expense.
For the quarter ended December 31, 2022, Annovis reported a net loss of $7.7 million, compared to a net loss of $5.9 million for the same period in 2021.
Financial Results for the Full Year 2022
Research and development expenses for the year ended December 31, 2022, were $16.5 million, compared to $8.5 million for the same period in 2021. The increase was primarily the result of an increase of $6.6 million in clinical expenses, as the Company incurred costs related to its Phase 3 study in early PD patients, its Phase 2/3 Alzheimer's study and an increase of $1.4 million in stock-based compensation expense. General and administrative expenses for the year ended December 31, 2022 were $9.0 million, compared to $6.1 million for the same period in 2021. The increase was primarily the result of an increase of $3.1 million in stock-based compensation expense.
For the full year ended 2022, Annovis reported a net loss of $25.3 million, compared to a net loss of $14.5 million in 2021.
$$$ talks!
Interim analysis for Phase 3 study of buntanetap for the treatment of early Parkinson's disease (PD): On March 31, 2023, the Company announced that it had received the results of the pre-planned blinded interim analysis conducted by a data analytics provider based on 132 patients from all cohorts collectively for which baseline and two-month data was available. As the interim analysis was conducted at two months of the six-month endpoint and only on 132 patients, it may not be indicative of the results at six months for the full patient population because as the trial progresses, clinical outcomes may materially change as patient enrollment continues and more patient data become available, or different conclusions or considerations may qualify such results once additional data have been received and fully evaluated. Based on the results of the interim analysis, the Company intends to proceed with the trial as planned in accordance with the previously established protocol.
So they have decided to stick with N = 450.
Could the problem be that the US campaign has simply been much more successful than anticipated, and if allowed to continue unchecked at the 50 US sites, would not leave a reasonable number of places available for the 50 EU sites?
They don't have the cash to get to 2026. They have enough cash to get through 2024. Since they can't sell pills, how are they going to get there? That doesn't sound like they're getting the best results they were hoping for, because they're talking about expanding the trial while the trial is still running, yet no PR hoopla about how well it's doing... No executive who has to raise money is going to miss that opportunity to talk things up publicly, and yet they're not. Doesn't mean the drug is dead it just means it's going to take longer and they have to raise some money without souring the milk of investor interest. Instead, a quietly and indirectly indicate a pause, not acceleration. There's your clue it's going to be a wait. Hopefully it's not because it's a bad drug, but because they just need some more money and resources, and of course, time.
"They have had an increase in patients and not enough study drug now, supply and demand."
I think they said "drug", when they really meant "places".
I think you are correct. As Marc has pointed out, the idea that they would be running out of the drug makes no sense. The email was not an official statement by a company employee, but came from a person employed by the trial site. This may have been a junior level person with little understanding and a lot of misunderstanding.
Could this be related? There are reports of drug shortages in the US, for example, from the New York Times: Drug Shortages Near an All-Time High, Leading to Rationing, nytimes.com/2023/05/17/heal.... This article says the problem is mostly with US-made generics: news.yahoo.com/why-us-drug-....
The company has since indicated they had enough applicants to fill the study
You don't talk about increasing study participant numbers if you have good results... You talk about increasing study participant numbers when you have soft results and need to extend a bit... Which may be behind the recent comment on believe that they are looking at 2026 before showing marketable results to investors.Meanwhile this also means you're going to have to raise more cash in the marketplace, probably by doing a secondary share offering since they are already a publicly traded company.
The implication in any case is that they might be having to go back to the drawing board on the current study to try and salvage or they need more time as they burn through their cash. At the rate they are burning through cash they might have this year and next year and after that their ability to raise cash is going to depend on the promise of Buntanetap, so if the drug is not coming along as previously projected then they have to find a way to fund the company and its activities for longer than expected, and if that gets out then maybe it'll be harder to raise money to get through the extra time... They have no actual sales, they're clinical late stage development company so their income is based on market capitalization and shares outstanding...
So they have to go back to the well to raise more funds, but who's going to invest in them if they're promises flagging?
Bottom line it means their timetables are having to extend and they have to find the money to fund the extra time as well as deliver more clearly good results.
So this bit about not having enough medication may be a bit of a dodge; the last thing they need is investors getting wind of an idea that the basis for their stock valuation and prospects might be flagging, because that also means it may be harder to raise money by offering more shares into the market, to get through the extended period they're going to need.... And this may be why their stock price has recently taken a big dive and it's down about 50% in the last few weeks...
In any case, they're anticipated target is now 2026, at least per the conversations at Yahoo Financial about what the company said, and I think they were talking about this med.
It might be Chinese whispers. But you would have thought that if the recruitment freeze is due to the preliminary results confirming participation numbers are sufficient, and the trial is "full"
that they would say so. And Ms Santoni would have said exactly that.
Instead of "they ran out of study drug"
Maybe the message from Annovis was clear, and explained that Full enrollment had been achieved, and it was Ms Santoni garbling it.
Unlikely. Possible, but unlikely
On their website they say that there are 100 sites, split 50/50 between the US and the EU. However, they don't say how the 450 places are distributed. The US campaign has been running since August. The EU campaign has only been running for a short time.
I think it's quite possible that the US campaign is at or very near the full mark.
So do I. But you would expect them to say that. Filling their trial quota is a good news story. Normally Annovis are not shy about good news
not the news I’m wanting to wake up to this morning. I am also in the trial and so far have noticed no improvements except maybe less brain fuzziness
how long have you been in?
2 months
That is exactly the same as my experience. I began taking pills in January.
not feeling good about this at all, was so hopeful going in
I did my screening visit on March 17th. On Tuesday April 4th I got the following e-mail:
I just wanted to give you a quick update on the Annovis study. All of your labs came back looking great! We are just waiting on the arrival of the study drug then we will get you scheduled for your baseline visit. As of right now we are looking at the week of April 17-21st. Do any of those days not work for you for a visit?
We will see if they really get the drug in that time frame. . .
Could this be the reason for the shortage?
Dosages: The 10mg and 20mg doses, while perhaps supported by preclinical and pharmacokinetic/pharmacodynamic studies, do not appear as clearly the most efficacious doses from the Phase 2a data. The 14-patient Phase 2a AD data, some of the “strongest” of the trial, used and 80mg/day dose. (Seeking Alpha)
That Seeking Alpha article is in error. 20 mg is the best dosage.
For PD or AD?
Well - it is correct to say
"The 14-patient Phase 2a AD data, some of the “strongest” of the trial, used and 80mg/day dose." That statement is not wrong - except there were 15 patients, not 14
For AD the only doses were 10 on 80mg and 5 on placebo. So , little surprise the 80mg dose had the best results
i thought the 'TRIAL' was already under way??? and you had been accepted and were already taking treatment (although you didn't know if it was a placebo)
New presentation posted on Annovis website. annovisbio.com/_files/ugd/b...
thanks
I had passed the initial phone call, was waiting to set up an appointment for the screening visit and was just informed that the trial has been “paused” for now. They didn’t know why….
I wish that I am wrong but seems to me that Buntanetap could meet the same fate as Prothena's PRX002. In my opinion it's not the demand-supply issue but something else which is being hidden by the company. There are chances that in the coming days they announce the discontinuation of the trial
I would be quite shocked if discontinuation of the trial were to happen.
Jeff's hypothesis:
Recruitment at the (currently) 35 sites in the EU is proceeding slowly, while recruitment at the (currently) 43 sites in the US is proceeding quickly. To give the EU sites a chance to recruit a reasonable number of patients, a temporary "pause" has been enacted at the screening stage for US sites.
I had sent them an email asking for the reason of holding the trial. They have replied to my email a few moments ago
This may just be regional - I've had progress getting into another site recently.
Just click on the user avatars. These are not fictitious accounts. They have all been here participating for years.
panicking daytrader
Welcome to the group Tanner. There are a lot of nice and helpful people here.
prnewswire.com/news-release...
ANNOVIS BIO TO HOLD LIVE WEBCAST TO REVIEW ALZHEIMER'S DISEASE AND PARKINSON'S DISEASE CLINICAL PROGRAMSNEWS PROVIDED BYAnnovis Bio Apr 13, 2023, 07:30 ETWebcast to be held on Thursday, April 20th at 4pm EDT.BERWYN, Pa., April 13, 2023/PRNewswire/ -- Annovis Bio, Inc. (NYSE: ANVS) ("Annovis" or the "Company"), a clinical-stage drug platform company addressing neurodegenerative diseases, today announced that the Company will hold a live R&D webcast to review its clinical development programs in Alzheimer's disease and Parkinson's disease.As part of the presentation, the Company will discuss why it believes buntanetap is uniquely positioned to address both symptomatic as well as disease modification in early and advanced-stage Alzheimer's and Parkinson's patients. Annovis will discuss its preliminary plans to develop the drug with the FDA for all stages of the disease, short and long term, and discuss the recently announced results from the blinded, interim analysis of the ongoing Phase 3 study in Parkinson's disease. Following the presentation, the Company will hold a Question-and-Answer session.
biobuzz.io/annovis-bio-embr...
Long transcript at link - describes reason for medication issues - key paragraph seems to be:
Maccecchini said, “In Parkinson’s disease, there was a significant increase in both motor function and coding speed, which supports the ongoing Phase III trial. It is expected to recruit all its patients this trial and we hope to have data by Christmas.”
I just wrote a very long comment, but decided to delete it. Ultimately, the results will speak for themselves.
The article says that they have accepted 385 patients so far (N=450) with 3 times more in the US than in the EU. So maybe a little less than 300 in the US and a little less than 100 in the EU, so far. The article also says that "this was complicated by too many bottles of the drug in Europe and not enough in the U.S. They have since been redistributed." Presumably, the recruitment pause (at the US sites) has now been lifted.
So, while they might have originally anticipated a more-even recruitment split between the US and EU, they now seem to be more-clearly focused on completing the trial sooner rather than later.
Regarding the interim analysis, the article says: Maccecchini also emphasized that earlier announcements of the company’s interim analyses were misunderstood, saying, “interim analysis gives probabilities, not data. It only gives a GO/NO GO determination. And it was GO.”
businesswire.com/news/home/...
“On June 3, Annovis announced it had reached full enrollment in the trial in a record nine months. Since the first patient was dosed in late August 2022, over 640 patients were screened and a total of 520 patients enrolled with 67 sites (43 in the United States and 24 in the European Union).
The phase III trial is a randomized, double-blind, placebo-controlled trial investigating the efficacy, safety, and tolerability of buntanetap for early PD patients on top of their standard of care. By lowering levels of all the neurotoxic proteins, buntanetap improves axonal transport (the nerve cell’s information highway), which has been shown to be the cause of nerve cell degeneration and, ultimately, death.
The record enrollment and low drop-out rate in this trial are believed to be due to the drug’s benefits demonstrated in the I/II trial:
It showed improvements in both body and motor function.
It is easily administered as a once daily pill.
It is safe and well-tolerated.
The study is expected to conclude in November with top-line assessment data available by the end of the year.
Annovis announced on June 20 the positive safety review by the Data and Safety Monitoring Board (DSMB) for its phase III trial of buntanetap for PD. The DSMB recommended that Annovis continue the trial as originally designed.
The feedback from the DSMB included:
There were no drug-related SAEs (serious adverse events).
Each AE (adverse event) was less than 2 percent.
The dropout rate was 6 percent – significantly below expectations.
Patients enrolled well ahead of the expected timeline: 9 months to enroll 523 patients.
The planned enrollment has been achieved and based on this DSMB endorsement, Annovis expects topline results by the end of 2023.”
Buntanetap for Mental Illnesses?
"put your own mask on first......'
The Iceman ‘on hold’
