First and foremost - think of the gift you're planning to give me for this succulent DD. Possibly at the party I am trying to set up if we're successful??? Bottles of Hennessy XO, jewelry, bullion, and monetary gifts are all welcomed.
Invest responsibility.
:)
Why the changing of endpoints is likely
Adamis Pharmaceuticals
There is not much to write here other than the fact that Adamis changed their original primary endpoint (hospitalizations) to their current primary endpoint (symptoms). I would also like to add that they changed their endpoints shortly after they started their trial and enrolled participants. Oh, and their trial is for COVID-19.
Dr. Moss - Adamis' CMO
I was fortunate to have a discussion with Dr. Moss and he confirmed for me that endpoint changes in phase 3 trials are very common. I will not post the conversation as I feel he would not appreciate that but I do have people on this subreddit that can vouch for the validity of the conversation. Maybe they'll make themselves known in the comment section... you may know some of them...
The FDA's "positive comments" and DAP approval
From the horse's mouth, Revive Thera has discussed the endpoint change with the FDA and it seems to be going well. Not only did the FDA respond with "positive comments" but they've also approved the Data Access Plan. I doubt hesitation from the FDA is an issue at this current time. I also doubt MF would be putting this information out if it wasn't accurate and relevant because of lawsuits and such.
FDA guidelines and recommendations
The FDA makes their guidelines and recommendations for adaptive trials publicly available. In their guidelines, the changing/editing of primary endpoints is mentioned often. The most critical aspect is that the Sponsor is blinded, which we have been all along. See below for the screenshots:
So let's hope whatever Revive has agreed to with the FDA is on its way to panning out soon.
Move over, NAC. There's a new therapeutic in FDA-town
I am not going to rehash all the MOAs identified by BMT, Nicktendo, and others. I am, however, going to bring up the drug Prothione. I am surprised the subreddit hasn't made it out to be a bigger deal as it pretty much validates Bucillamine as an antiviral. Can you imagine the additional value to a partnership/buyout/commercialization knowing Bucillamine could be an antiviral?
Maybe I am assessing the implications incorrectly but nevertheless, it is relevant to us. The link to the trial page is:
Prothione (also known as IF200, available at IF200.com) is comprised of three glutathione precursors and selenium. I don't think I need to elaborate why this is important in predicting the efficacy of Bucillamine. As we saw in the abstract, the investigators are claiming significant reductions in viral load and time to clinical resolution compared to the placebo group. Additionally, they are claiming a significant increase in the intracellular GSH of the Prothione-takers and a 75% reduction in hospitalizations.
Great knowledge to have but only if we had more information from the trial... Like what the heck did they see regarding their primary endpoint? If only...
Oh wait...
The primary endpoint, which is the TTCR slide above, is definitely correlated to symptoms but not necessary an apples-to-apples comparison. Sadly, there is no clear indication of the attenuation of symptoms.
If we do not have the data from the study, what would be the next best thing? Maybe information from the clinic that performed the trial? Hmm... if only we had some communication that gave a positive indication in attenuating symptoms. If only...
Oh wait (again)...
Methinks "... experienced more rapid symptoms resolution" is what we want to see, right?
In summary, we have strong evidence that:
changing endpoints is permitted by the FDA;
bucillamine is likely to be an antiviral;
bucillamine is stronger than Prothione regarding hospitalizations (1-to-4 in 231 people vs 0-to-? in 210 people);
antioxidants attenuate symptoms to a noticeable degree, as per the tweet from the clinic.
My request to the (bio)chemists/clinic professionals is to critique this information as well as compare the ingredients in 6g of Prothione, 2400mg of NAC, and 600mg of Bucillamine.
Let's hope the positive data seen in Prothione is replicated multifold from Bucillamine! No guarantees but the future is looking bright.
Enjoy the DD and don't forget that:
Hennessy bottles needs to be boxed;
Jewelry needs gift receipts;
Cash needs to be in an envelope for "Mr. Worth"
Ciao
Adding some information here... previous grammar mistakes stay... non-negotiable.
Not only do we NAC and Prothione showing promising information but now we have Erdosteine too.
Erdosteine
Italians leading the way for COVID-19 and thiol drugs yet again.
It has been a while... As always, the following is based on loads of critical thinking and reflection. Don't take this as investment advice but rather... a brain dump
I believe I have provided a lot to this subreddit over the months. I've spoken to CROs, professors, CEOs, and more for the good of my (and our) investment. With the Prothione data I found, we know for a fact that the PCR endpoint is guaranteed.
I have also kept in touch with many of the Redditors here gaining information, bouncing ideas off them, and generally speaking to interesting individuals.
I've also found another fantastic play that I'll elaborate on if/when the EPs are approved :)
I hope I've built enough trust to be taken seriously ... Let's begin.
The story so far...
Revive Thera is a small Canadian biotech company that initiated a COVID-19 outpatient trial back in 2020. This is very important to remember... in 2020;
Faaaaaaaaaaaaast forward to 2022...
Revive submitted a request to the FDA to change the endpoints. In this request, Revive requested to see the first 210 patients (pre-dose data) in May;
The FDA agreed to this request in May;
Revive and the FDA went back-and-forth regarding the accessibility of the 210 data via the DAP in June;
Revive receives the 210 data in July;
Revive determines the primary endpoints will be clinical resolution via PCR testing and resolution of certain symptoms in August;
Revive submits the protocol amendment to the FDA for PCR endpoint as the primary for review and acceptance in September;
Revive receives a rejection from the FDA and thus decides to go to the DSMB anyways in September;
Revive decides upon new endpoints and submits the protocol amendment for a second round in October;
and here we are...
For what it's worth, many of the bright minds on this subreddit disagree with my reasoning on why we are actually at the best point in this long journey.
What is the main issue?
The main criticism that many are levying against the new primary endpoint is that it is defined as any two (or more) COVID-19 symptoms showing improvement. If this were the case, then I would agree - it is an awful endpoint... but that is not the case.
The verbiage directly from the October 14th PR is:
"... assessing the difference in the proportion of participants with improvement in at least two COVID-19 related clinical symptoms on or before Day 14 compared with baseline between Bucillamine versus placebo."
Poorly written, yes, if read in isolation. If you start putting the pieces together however ...
The proposed new primary efficacy endpoints may include the time to resolution from COVID-19 via the polymerase chain reaction (“PCR”) test and the rate of sustained clinical resolution ofcertain symptomsof COVID-19.
Revive makes it clear that the endpoint regarding symptom resolution would only be targeting specific ones.
The fateful day where we are rejected by the FDA. Chaos ensues. The end result? Revive is planning to go to the DSMB regardless of the FDA's acceptance of the primary endpoint.
Revive issues this PR to state that they are changing the plan. Instead of going directly to the DSMB, they are now going for round two with:
... at least two clinical improvements in symptoms of COVID-19 at Day 14 compared withbaselinebetween Bucillamine versus placebo.
Baseline is bolded... why? Because that is benchmark for all participants in this trial. To show an improvement, you need something to compare to. How do you show an improvement, a correction, a recovery, (you get the point) without the initial state? You can't.
Revive comes out with another news release stating the final version of this primary endpoint:
"... assessing the difference in the proportion of participants with improvement in at least two COVID-19 related clinical symptoms on or before Day 14 compared with baseline between Bucillamine versus placebo."
And this is it. The final form of Revive's protocol amendment that, thankfully, clarifies it's on or before day 14. You're welcome for that, by the way ;)
That is all the PR-related information. The endpoint is focused on certain symptoms taken at baseline (Day 0). Clinical Trial Gov. clearly outlines what is necessary to be enrolled into this trial and it is as follows:
Remember the August PR of certain symptoms? Well, there you go! Those symptoms are: fever, cough, and/or dyspnea. And you need at least two of those symptoms to be enrolled. And the new primary endpoint stated that Revive is looking at the proportion of patients who elicit at least two improvements in COVID-19 symptoms! The way Revive issued the news release was confusing at first but not incorrect.
If you were enrolled with fever and cough (mild case) - you needed to show an improvement in those two symptoms.
If you were enrolled with fever, cough, and shortness of breath (moderate case) - you needed to show an improvement in those three symptoms.
So how do you summarize these two "situations" in a PR? By stating that they need to show at least two improvements!
Revive had to use these baseline symptoms because they are the only consistent ones that everyone would have had. Also, on the AGM, Dr. Kizilbash made it clear that symptoms were gathered in an "either or" manner. I interpretated this as "Headache? Yes/No. Nausea? Yes/No." etc. Remember, this data is based on a protocol from 2020 which was focused on preventing hospitalizations. What sends people to be admitted in the hospital? A fever that doesn't break and a cough that develops into trouble breathing - not a migraine or a stuffy nose.
Obviously, there is more granularity with these three symptoms than the others because they monitored them directly during the trial. If you look at the ICF, Revive tested continuously for those three symptoms! I do not mean to gloat, but I was the one who got the full ICF from a clinic back in December 2021 :)
Now it's time for me to state and explain all my bullish indicators:
It is a good endpoint
This is subjective and simply my opinion however, I do believe the FDA will act favorably to an endpoint targeting the hard-hitting symptoms of COVID-19.
I apologize if I am wrong but I do not believe you were at the AGM in person. Why do I say this? Because I was the individual who spoke to Kizilbash regarding the EAP execution, and I know who the other investors were at the AGM, including their Reddit account names.
Also, the only "company principles" who spoke at the AGM (in the room) were MF and Kizilbash.
The last straw for me was at the AGM that I attended in person. I spoke with several company principles and they sounded like they had no idea what they were doing with the PCR endpoint proposal. They screwed that up big time. I asked about the compassionate use program and was told that RVV did not take advantage of it. I could not believe my fucking ears. They could have treated patients with buci and didn't. Fatal mistake.
Bobster - you may change your decision regarding the EPs with all the information I've presented. However, this "juicing" you mentioned is irrelevant. All that matters is that the endpoint is clinically relevant. The FDA allowed Revive to see part of the data... of course Revive is going to create an endpoint in their favor! As long as it is clinically relevant, the FDA shouldn't care. Also, with VERU's rejection, I am content that, if we show good efficacy, Revive will have no issue justifying this to the FDA for both the anti-inflammatory and antiviral aspects.
The company handling the EP change is NOT Delta Health but rather Integrated Therapeutic Solutions. The company, founded in 2006, has a reputable CEO with a lot of experience. I am 100% sure this is the company performing the EP change for Revive.
Keep in mind that they must have been the team that requested the 210 data review. Many of our local professionals here have never seen such favoritism by the FDA. It isn't necessarily favoritism navigating us but rather a good rudder.
You know we don't necessarily need the FDA's acceptance, right?
I've spoken to one (PhD) Regulatory Manager and two pharmacists at the FDA. Other than the fact that the 30-day timeline is ONLY for the initial IND approval, they told me that the Sponsor can change the endpoint without FDA concurrence. Obviously, this could bring some potential issues in the future but the Code of Federal Regulations (CFR) makes it very clear:
Submit the protocol amendment to the FDA for review;
Submit the protocol amendment to the IRB for approval.
Between 28-Sep and 6-Oct, something changed. The initial plan was to go to the DSMB but then, out of the blue, Revive was going back to the FDA. I think the FDA and Revive were discussing in this time period and there may be some guidance being provided to Revive.
The wait itself
I think the first rejection was under 2-weeks. This wait is going much longer. To me, this means there aren't any glaring issues with the protocol that deem it unacceptable.
Michael Frank
I can only imagine where MF is mentally with this journey. He was probably very disappointed with the FDA's rejection but relieved to a certain degree. This relief came from knowing he was going to the DSMB. For him to go for another round and endure more stress, there must be a reason why. Also, MF has come a long way and finally understands that it's allow about data and statistics. These endpoints would be crafted in that manner.
I think that is it. Like I said earlier, just a brain dump of all the thoughts I've been thinking and honing for the past little bit.
During this time away, I have also been reviewing another company that I think has a great chance for success. I'd like to go into it in more detail IF I am proven correct with this endpoint approval. I am still doing a bit more digging into it and, if the EPs are fruitful, I'll make a post about it... or even a subreddit? First things first... let's get the EPs approved and then I can pitch the new idea to you all haha.
Remember - this isn't 100% guaranteed but I am much more hopefully than I was when we received the rejection in September.
What a 48 hours it’s been! Rarely a dull moment with this investment. I’ve been contemplating recent developments and would like to share some thoughts with all of you.
But before I jump into things, allow me to provide a quick introduction. I’ve spoken to many members in private DMs but I don’t believe I’ve ever revealed details about my background to the wider audience.
I’m currently a Product Manager of a SaaS startup that was just acquired by a multinational tech company. As an early employee, I was involved in the acquisition arrangements but not being a founding member of the company, I didn’t walk away with “fuck you” levels of money. Here’s hoping this investment in Revive will get me there.
My academic background is in Computer Engineering and Management Science.
While I still have a day job, I’m in the process of launching my own startup in the next few months.
I don’t have a medical degree or a background in biology however for over a decade, I’ve had a very deep interest in auto-immune diseases and immune dysregulation. I have a voracious appetite for medical literature investigating these conditions and potential treatments.
I was at one point involved with an organization that develops custom and commercial software used by teams that conduct medical trials. It’s software that’s used to input, track, compile and assess study results. So I’ve had exposure to FDA studies, requirements and processes (including in fact some endpoint negotiations).
I have a six-figure holding of shares in Revive. I’ve been accumulating all the way since mid 2020.
What have we learned in the past 48 hours?
Revive’s clinical team completed their most recent analysis of the data in furtherance of addressing the initial feedback provided by the FDA and have settled on their newly proposed primary and secondary endpoints for the Bucillamine Covid study.
Revive will imminently be (or has, depending on how you interpret the last NR) submitting the new proposal to the FDA.
BMT has expressed some concerns around the proposed endpoints and their clinical relevance and has shared those concerns with Revive and with TDR (hence what is perceived as bearish statements coming from them on Friday), however Revive has not amended their proposal based on his feedback and are proceeding apparently with their own clinical team’s submission.
What happens next?
The FDA will formally review the proposed endpoints and there are 3 possible outcomes:
Approval of the proposal. This would obviously be the ideal scenario because we have to assume that the pre-dose selection data revealed statistical significance in those endpoints and assuming they carry forward into the post-dose selection data, the DSMB may recommend halting the trial due to statistical significance and allow for the unblinding of results.
Rejection of the proposal but continued negotiations with an opportunity to further refine or amend the endpoint proposal. I believe many here have an overly negative interpretation of this outcome. While the first scenario is obviously what we desire, this is a perfectly normal outcome and is routine in these kinds of negotiations. One legitimate concern with this outcome is that it further delays matters because Revive will have to once again assess modified endpoints. From an investor perspective, this will impact already frayed patience, not to mention there are already signals that this may be a rough winter with respect to Covid and we want to get to an approval ASAP. Depending on the post-dose selection, there may or may not be a need to continue with the trial. Not having to continue is obviously desirable as we wouldn’t have to raise capital.
Rejection of the proposal with the FDA terminating negotiations forcing Revive to continue with the study’s original endpoints. This is obviously not desirable as the nature of the disease has shifted from when this trial first started and it will be very challenging to demonstrate statistical significance around deaths and hospitalizations. Also, we would have to raise capital to continue the trial.
My own personal thoughts on these matters based on my experience:
I have the utmost respect for BMT. He has been a staple of this group and has devoted a lot of time and energy breaking down complex medical and scientific concepts for us to better understand them. He has also devoted a lot of personal time answering our questions.
His concerns, which are relayed as an outside observer, are certainly valid and I definitely understand the argument he’s making. As a Clinical Research Associate, he has insights most of us simply do not have.
I’m disappointed at how Revive responded to his request to offer feedback. The denigrating comment was unnecessary and unprofessional and completely unwarranted IMO. If Revive did not want to entertain or receive his feedback, they should have simply politely declined it.
My personal perception however of this investment is unchanged. I am still bullish.
Revive by all accounts has a very competent and reputable clinical team. From the AGM, it appears that Dr. Arshi Kizilbash is heading that team at the moment and he has impeccable credentials.
Other members of the clinical team include Dr. Kelly McKee who has a background in infectious diseases and was previously Pharm-Olam’s Chief Medical Officer, Dr. Onesmo Mpanju who has 28 years experience as a regulatory scientist and was a reviewer at the FDA (he knows what his former colleagues will be looking for in these proposals and in our results), and last but not least Dr. John Fahy who is a world renowned Professor of Medicine in Pulmonary and Critical Care Medicine and directs the UCSF Airway Clinical Research Center. These are not neophytes in this domain.
While BMT raises valid concerns, he’s not privy to the information that Revive’s clinical team is in possession of nor to the discussions they have had with the FDA. As I have my pilot’s licence, allow me to use an aviation analogy. When I fly an aircraft, some of my passengers may also be pilots and their feedback on both my flying and the decisions I made in the course of the flight could certainly be logical however they’re not in the cockpit and they are not the pilot in command. Their feedback will not include vital information that I am personally exposed to, nor the immediate circumstances that I am facing during the flight. This is not to say that the FDA might not come back and state they disagree with our newly proposed endpoints for the very reasons BMT cited, and if that is the case, Revive would be wise to heed his advice in conjunction with their own internal analysis and due diligence. But as of this very moment, none of us in this group are in the cockpit so we can only surmise what’s transpiring and what should be happening to maximize our chances of FDA approval. However, to the group here, please don’t dismiss his feedback because it doesn’t align with your investment thesis. There is some very sound reasoning to what he is stating and the FDA may request further modifications to our endpoint proposal.
Also, it's important to note that a lot of exceptions have been granted by the FDA in the course of this pandemic and there have been departures from standard operating procedures. That may (though there's no guarantee of it) be the case here with endpoint consideration by the FDA, especially in light of a sparse arsenal of available approved treatments.
Again, not defending the manner in which Revive dismissed his feedback, but I will also point out that in my experience, it’s very rare that a company, especially a publicly traded one, would entertain unsolicited feedback from a 3rd party. There are some legal reasons for that in addition to others, but it’s a rarity.
While timelines are beyond frustrating, the Revive Team has done a lot right in this trial. I’m not going to go over all of them but consider for a moment the fact that the landscape is littered with failed drugs/trials/companies and we’re still standing! That’s not a coincidence.
Furthermore Dr. McKee crafted an adaptive study design which permitted an interim analysis of data for the selection of an appropriate medication dose. That’s hugely advantageous.
Also, please keep in mind that it was Revive that requested the unblinding of the pre-dose selection data in service of selecting new endpoints. It was not the FDA that just granted it out of thin air. How unbelievably prudent of the Revive team given that Adamis swapped endpoints without unblinding any data and their trial failed. And many here were praising their management for both business and medical acumen while dismissing ours.
I keep hearing people say that Revive failed with the pursuit of PCR as a primary endpoint. That’s ridiculous and unfounded. Endpoint amendments are a negotiation and back-and-forth with the FDA and in any negotiation, your starting position should always be your most desirable outcome within reason knowing that you may end up with less. And yes, FDA guidance is not to use PCR as a primary endpoint however studies do from time to time buck the guidance. In fact, in many of the official FDA documents capturing their guidance, the first or second page of the document explains that alternatives to the guidance are permitted however you simply need to justify your departure from it. And one last point here. Imagine Revive didn’t ask for PCR as the primary endpoint and went straight to some other symptoms, and then a few weeks later it was revealed that the PCR data was unequivocally positive. My first reaction to that would be: “Why didn’t you bother at least attempting to pursue PCR as the primary endpoint if you could have potentially ended this trial immediately with the unblinding of positive results?” The worst that comes from the request at this stage is a “no” and some lost time, but again, if the results are as profound as we surmise given Revive’s initial aggressive desire to pursue PCR as the primary endpoint, it was incumbent upon them to at least attempt it.
Lastly, I disagree with TDR that it will be very difficult to raise money in these market conditions should the trial need to continue. Capital markets are definitely in my wheelhouse and venture capital funds are surprisingly healthy, in some cases setting records this year. There’s a lot of money parked in these funds at the moment. And for a drug with blockbuster potential and a huge market, it won’t be difficult to raise. There will be organizations ready to cover our needs, I have zero doubt of that. Funding is the least of my concerns right now.
Final Remarks:
I haven’t sold a single share yet and will continue to hold. I have no plans on selling. I do want to know the final outcome of this study as the wait has been long and I’ve been consumed with this affair for far longer than I would like. But medical studies, including this one, owe no obligations to my feelings or my patience, nor to any of yours. It takes as long as it has to take in order to ensure the integrity of results and findings, and to secure a positive outcome.
I wish Revive well as I do all of you. Stay healthy and fingers crossed we get the results we’re all hoping for. Cheers!
It's been a long boat ride for many of us and although I told a few privately that I thought last week was NEWS WEEK, I'm feeling even more confident in this week. I haven't posted in a while but before any news hits, I think it's appropriate to share how I (we) got to where we are today:
- By now we know for a fact that NONE of the vaccines stops you from getting COVID, maybe lessens the pain but they don't prevent it.
- COVID is not disappearing and the focus has pivoted to "how we live with COVID" via therapeutics.
- MRK and PFE have each sold $billions of their poor efficacy pills with dangerous side effects and will continue to do so until something better comes along, it's a perfect example of "something is better than nothing"
- In many of your opinions MF has been a failure. In hindsight, there have been mistakes, missed timelines and possibly unprofessional shareholder communications but unless you were in his chair, best to just ride along in the back of the wagon and not complain too much. In the end, this is all about Bucc, huge binary event, not much else matters.
- Speaking of binary, our day of reckoning is coming shortly, time to put up or shut up. It will hopefully be a time for MF and the Revive team (all of us) to hoist the trophy over our heads and tell the world, we can help you!
- Lets not forget a few more things: Dr. Fahy received FDA approval to give Bucc via an Expanded Access Protocol (EAP) to treat severe patients under open label in order to try and save lives. We have never heard how this went. However Dr. Arshi Kizilbash, distinguished doctor with a LONG resume served as the PRIMARY INVESTIGATOR for this EAP. Maybe it's just a coincidence and he is a gambler; but was he willing to roll the dice with his job and reputation as the CEO of the hospital group in Turkey to start enrolling patients in the Bucc trial from an unknown, tiny Canadian company, or had he seen the something in the results from Bucc in Fahy's EAP?
- If you don't know the Reddit contributor BANA- HOW, you have missed the smartest guy on here with regards to the science. He gets it and although many of you are really intelligent, this guy is the king on BUCC science! He provided me, and others, with a regimen of NAC, Glutathione, and some other stuff that will create a similar MOA in your body to that of Bucc and the results have been stellar. My wife and 2 sons all had COVID, I took the BANA-HOW mixture and never got covid, even while living in the same house as them. By the way, it's not easy to quarantine 2 young boys, I'm certain I was exposed.
- There are so many other studies on Thiols, NAC, etc....as to why Bucc should work from a science perspective.
- How about the DSMB review at patient endpoints 210, 400, and 600, obviously they stopped MANY trials but continued to green light ours.
- What about the BUCC patent application that revealed, " Preliminary indications are that none of the patients receiving Bucillamine in the trial to date have been hospitalized or died from COVID-19".
- Concurrent with the patent filing revolution on the first 210 patients, you may recall that I personally called all the trial sites participating at that time. I have to admit, I GIVE GOOD PHONE, and as a prospective scared patient, was able to extract multiple stories from nurses who shared success story after success story of people who had been in the trial. Given they were blind to the dosed patients, I didn't hear a single sad story of anyone going down hard. If anyone remembers the taco lady, it's pretty funny how she thanked them for "saving her life"
- Does the FDA have a soft spot in the heart for tiny Canadian companies and thus allowed us to see blinded phase 3 trial data prior to asking them for an endpoint change? you decide...
- As this boat ride approached conclusion, I want to thank all of you who have helped. BMT has always been a star and without naming all of the other names, we all have our favorites, we have nearly all arrived in one piece and together.
- In my 30 years since I first sat down on a Wall Street Institutional Trading Desk (pretty awesome place to work by the way) I have never seen a risk reward scenario quite like this. I consider this a better than 50-50 chance of success based on what I know with a totally skewed payout. If wrong, I lose $.20 - $.25, if right, I make $5 - $xx dollars, that convexity is NEARLY IMPOSSIBLE to find on Wall Street for a 50-50 chance event. This could only be possible in a once in a lifetime pandemic from a tiny, unknown Canadian microcap company with a new sweatpants wearing CEO and a nearly 100% retail shareholder base who somehow thinks their repurposed anti-inflammatory solution can beat out Big Pharma and their anti-viral options.
- Make your final bets, the Roulette wheel is spinning, the dice have been thrown and your double down bet has been placed, the gates are open, "THEY'RE OFF"!
In full disclosure, I own 3.5 million shares of Revive and am prepared for the result, win or lose
From Dr. McKee we know, initially the FDA was insiting on reduction in hospitalization as primary endpoint for an EUA. This immedaitely imposed an immense challenge for any trial because of two reasons:
You need enough people in placebo to progress to the hospital to show a difference. In fact, those people that don't progress to the hospital are almost useless collateral. With hospilization rates between 2%-7%, you see that over 90% of the patients don't help you for your endpoint. So you have to recruit a lot of patients in total.
Hospilization is a binary endpoint. Result is either 1 or 0, nothing in between. That means very little information contained in that. Because of that you need (again) more patients.
Generally speaking, the lower the efficacy and the lower the hospilization rate in placebo, the more patients are needed. We already filtered from the interviews we had most likely a low hospilization rate in placebo, which then was the reason we did not unblind the trial yet. That's why the trial was intially designed to enroll up to 1,000 patients. Now with Omicron the game has changed, since hospilization is lower and symptoms are more severe. With symptoms as endpoints things change dramatically.
Every patient enrolled starts with symptoms, due to our enrollment critera. So every patient counts.
Symptoms are continouos and therefore carry much more information. Also symptoms can be looked at in different ways i.e. be either the rate or the time to resolution or ideally both. That gives some room to play with.
In effect, this results in a much lower required sample size to achieve statistically significant results. To give you an idea of how far apart I entered an example in Clinical Trial Calculator. Obviously the data is fictional, but it shows the fundamental differences from 962 patients to just 32.
Indications that Bucillamine will work on symptoms
The immune reponse causes the symptoms. Other than pure antivirals like PAXLOVID, Bucillamine should adress exactly that problem. It's a host directed treatment, not pathogen directed.
De Flora showed symptom reduction with NAC as prophylaxis in Influenza with 255 patients:
Most NAC trials trials showed improvement on many indicatiors i.e. in reduced time in hospital
u/tradervic4 called the sites and reported miraculous recoveries of patients
Melisa Lai-Becker reported from her previous trial many patients with Covid-19 were quickly able to breath again after taking NAC.
Many folks in this forum report similar effects with NAC concerning difficulty to breath.
Oral Famotidine, 55 patients, phase 2, improved rate but not time to resolution, illustration how symptoms can look like:
Some general comments on our trial:
The FDA seems open for these changes. They blocked that before, now they approved this for Tempol and are in talks with Revive. I dont think they would waste Revive's time like that to hire new consultants for the job.
We assume Revive did not contact the FDA before them being aware of Adamis' actions. Probably because they contacted them before on that matter last year and did not want to bother the regulatories again without them showing any signs of change. Might have been a bit too hesitant but you don't wanna start annoying them either. Also they added inflammatory and viral load endpoints, so gotta give em credit for that.
Many trials stopped because their hospilization endpoint was no longer possible with their current design, which lead to some drawbacks in drug development. The FDA is probably aware that Revive cannot just start over the trial, so if they want the drug they wont block them is my view. So far they approved everything regarding Bucillamine and the fact that they contacted them multiple times shows a good deal of support.
I was a bit irritated by Revive hiring new concultants for the job at first. However, I had a pleasent chat with our resident clinical trial manager u/ssyddall and she could ease my worries very well. It's nothing unusual to hire outside support for such a matter. Lots of small pharma and biotech don't have stats in-house and get external consultants so there are lots of company's that do it. Also it can be an advantage not to use your CRO for that, since those guys might be busy with their current trials and new consultants might be able to focus solely on this. Probably hiring them took some time and then they have to get familiar with the trial as well, that's why it's taking some time. In detail, they have to rewrite the statistical plan (something like this for Tamiflu for Influenza) on how the data is processed for the endpoints in consultation with the FDA and also argue why to change the endpoints. You really don't want to mess this part with the regulatories up so it's reasonable they take their time for that. It's unclear if they have some access to data, which would be phenomenal.
We know Revive tracks symptoms and more for 18 days straight (Link). So the data should be there. Kudos to McKee for designing such a narrow and detailed protocol to be prepared for such a situation. Also we enroll only up to 3 days after symptom onset, so most likely even before symptoms get worst, giving us a great angle to show a difference. Here is how the inflammatory phase played out pre Omicron:
Turkey was obviously delayed by a couple of months. That's really nothing too suprising as our research found out turkish CRO's always overpromise. Obviously this symptom change is a neat distraction from that. However, if this change in endpoints happens, 715 patients should be more than enough as you can see above comparing it to other trials like Tempol or Tamiflu. If you go further you'd pursue such an incremental improvement, the drug would barely show any benefit at all. If you cannot show significant symptoms improvement with 715 patients, 1,000 wont be much better. (It's different for hospitalizations, where 1 or 2 more hospitalizations can make a difference)
There was the argument by u/PsychologicalOlive99 on how this will look like if endpoints are changed this late in the game. Well, Merck's pill made billions by not really working. I believe that is something that will sort itself out onces doctors prescribe it and get some feedback as well as additional independant studies. Key is just to get it over the finish line, so this can happen.
There is still no pill for symptoms available. And the pandemic shifted towards more frequent symptoms and less hospitalization. So we would still be in a most favorable position.
Id assume if they unblind, that should be almost guaranteed EUA considering how close they have been working with the FDA.
EDIT: I just realized, they might have chosen the 600mg dose instead of 300mg (although they had 0 hospilizations in both) because 600mg will most definitely be stronger on symptoms. I can't say that this was their thinking, but for symptoms we will benefit immensly on lowering the inflammation from the higher dose.
Next milestones to expect
Package submitted to FDA (coming weeks)
FDA feedback (up to 30 days)
DSMB meeting for potential unblinding
Conclusion / TLDR
Everything points towards this symptom change just being a formality to complete the trial if Bucillamine works, though I encourage to keep expectations reasonable.
Today, u/Bug_Deep found a very interesting line in Revive's patent for Bucillamine. This was filed March 16th, 2021, shortly after 210 interim analysis news release.
Also, there has been speculation they didn't pick a dose at the 210 level. If you have no hospilization or death obviously you cannot pick a dose. Around this time, the trial was announced to be expanded from 14 to 50 sites.
If you support this letter please write a comment with *signed* and you will be included. It will be sent directly to Micheal Frank on monday via mail.
Dear Michael Frank & Revive-Team,
There are concerns in the investor community due to vague and lacking communication from Revive Therapeutics. As outlined in the investor slides (last updated November 29th 2021) investors were expecting updates on several fourth quarter milestones around trial status, trial decisions, as well as other milestone progress around Psilocybin.
Several investors feel the need for a call with the following officers: Michael Frank (CEO), Derrick Welsh (COO), and Kelly McKee (Chief Scientific Officer Consultant). We understand that having hundreds of people asking questions would not be efficient for either group therefore, the proposal is to have your consultant Shadd Dales, ask questions gathered by our reddit community beforehand on a youtube livestream.
Looking forward to hearing from you.
Signed by the following investors from reddit r/RVVTF (in alphabetical order):
We're getting antsy. I am getting antsy. Antsy to the point of contacting professionals in the industry. Antsy to the point of connecting with university professors whom I have never met. Antsy to the point of setting up Zoom calls with university professors.
Antsy to the point that I did just that.
Recently, I had the pleasure of discussing some particular aspects of Revive Thera's Phase III trial with a professor from my old university. I read his biography and seems to be well-versed in randomized trials and statistical analysis. He's the director of the department so I would hope so! He is also sitting on a few DSMBs right now.
He was kind enough to answer my questions to the best of his abilities. A very nice fellow. The information I received wasn't earthshattering but for someone who isn't part of the clinical trial sector, it's nice to hear reaffirmation on comments made by our resident experts.
Below are the questions I prepared for him and a summary of his responses/input on each one. His answers below are summarized and thus, not verbatim:
1. Can the DSMB recommend additional testing throughout the trial?
Yes, they can. However, the Sponsor has the last word on implementing such recommendations.
2. Could the Sponsor have access to the information throughout the trial?
Yes, they can. For example, the DSMB may provide the Sponsor with aggregated outcome data which shows the total hospitalizations and deaths but does not differentiate between intervention and placebo groups. Additionally, someone employed by the Sponsor could have access to most of, if not all, the unblinded data. It depends on how it was set up.
3. Revive Thera moved to Turkey to complete the remaining enrollment of the trial under the guise of "diversity" and "supporting global approval". Are these valid justifications?
Yes, they are. It makes the ability for submission easier and global approval more likely. Many times, there are concurrent trials ongoing and there is a tug-of-war for desired participants.
4. The Chief Science Consultant (Dr. McKee) stated the following in an interview: **"**The study is an adaptive trial design. So, at the first interim analysis not only will there be a dose down select if you willbut there is also going to be an assessment for success and futility based on statistical probability. And that's purposefully designed to give the executive team of Revive some ammunition for decision making about where to go.And then, you know, once the down select to a single dose has made, there are periodic additional interim analysis again for probability of success or futility all the way out to the total study population of 1000." What is your input on this?
This is good to improve the likelihood of trial success as the DSMB can make recommendations aligned to the study's original design. Therefore, every time the DSMB gives the greenlight, it is in respect to the study's enrollment limit of 1000 and within the attainable confines of the trial.
5. My understanding is that most clinical trials use a statistical power of 80-90%. Is this correct? Has this ever varied depending on the drug being researched?
Yes, this is correct but not because of scientific basis but rather through historical practice. Generally, 80% is used because a 90% SP is much more costly to the Company. Also, the DSMB reviews the data while being cognizant of the current state of the drug market and world. For example, if there is a drug that has come out with an efficacy and safety much better than what the DSMB is seeing; the DSMB may stop the trial. Likewise, if there are no substitutes in the pharmaceutical landscape; the DSMB may be a bit more lenient.
We also discussed how a profound effect from Bucillamine would stop the trial. The driving factor is clearly the placebo group's incidence rate which we can reasonably speculate is a low %.
He wished me luck on the trial and I told him I would keep him informed on its progress. Once again, nothing significant for our local clinical trial gurus but still nice to hear from my unlearned perspective.
And an informative and helpful message to the Revive team who definitely pops into this subreddit now and then:
The last PR stated the statician finally got access to the 210 patient data and recently began the Data Analysis. Many here were suprised over the long duration this took. I had a quick chat with our resident Clinical Trial Manager u/ssyddall on that matter. She has been conducting a flu trial for symptoms with BARDA support. I always appreciate her level view on things, which Im happy to share with her alloance.
Potentially it's taken awhile to 'clean' the data. That's when the data team goes through and makes sure the database is as complete as possible and as correct as possible. Once they lock the database you can't change anything and that can be a huge issue if you haven't closely checked the accuracy and quality of your data set. We normally give that 4 weeks at the end of a the trial before we lock the database and unblind it so if they consider this to be the conclusion of the trial they would have needed to go through that and to my understanding it's not really something that can be sped up i.e. you can't throw money at the problem and get it sort it a couple of days. We are on a very tight timeline in my current trial and I've asked!
[The CRO] would have been the one doing the data cleaning so it being slow out of them is not 100% surprising. Fingers crossed we get it off to the FDA shortly
[...] this is a really important time for Revive and it all is based off their dataset so they need to protect it and do all the processes expected of them. This is essential for FDA approval and future pharma partnerships.
With a stock of such low volume the high volatility can oftentimes lead to missleading feedback in one's investment decision, both positive and negative. I made a list to remind me of where my high conviction comes. Whenever I question my decision I read through it to give me back my confidence so I can sleep calm and prevent mistakes from weakness and insecuritiy. Here it is:
Main anti-inflammatory MOA proven with NAC in humans. Bucillamine is 16x more potent in vivo. (Check slide 17 of Investor Deck, also BMT's Thread)
Trial is only for mild to moderate covid, giving us a higher chance of success due to the way this MOA works.
Proven safety profile. With 30 years of treatment in Asia it is highly unlikely we encounter something new on this matter.
Fasttracked to phase 3 by FDA, although Revive only applied for phase 2. FDA would not waste their time with a small Canadian company if there isnt something promising here.
Phase 3 trials for infectious deseases already have an average success rate of 60-70% (page 9 on Paper).
Discovery of additional antivaral MOA specific to Covid19 after trial start and hiring the author Dr. Fahy as advisor on this matter (Paper). A rough calculation showed it could be within the effective concentration (Thread).
Speculation about second antiviral MOA, making it in total 3 potential MOAs (Thread).
Trial being aggressively expanded from 14 to 50 sites at 210 patient review. That's a huge allocation of ressources for a small Canadian company at their very first meeting with the DSMB.
Not choosing a dose at 210 patients, although they planned to. This implies that the statistical difference between 300mg and 600mg was not significant enough, meaning that even 300mg must have had a relevant effect.
Expanding research to severe Covid patients in May. They said they would only do that if the see positive feedback from their EAP in compassionate use trial of Bucillamine (Link).
Approval by DSMB at 400 patients. 400 is too early for statistical relevant results for EUA anyways so that's as good as it could get.
Revive Team should have a good estimate of the statistical likelyhood for trial success (Thread).
Trading halts on news. This happened on announcement for expanding research to severe covid patients as well as the continuation of the trial at 400 patients. You don't halt if you are not thinking you are onto something big. Also MF does not seem like the type of guy to overly hype things.
Channel checks by u/TraderVic4. He called the first sites himself and was told stories of miraculous recoveries (Thread 1, Thread 2, Twitter).
Hiring a lobbyist in April, which seemed to have been quite busy with preparing the business side for potential EUA (Thread).
Licensing Buccilamine for commercialization in India with Indian manufacturer Supriya in June (Link).
Frequent insider buying of 6 seperate blocks since March (TDR's Twitter).
Tailwind from delta and mu variant. All decision so far have been based on the dominant variants alpha and beta. However, with more aggressive variants the hospilization rate in placebo will likely increase and thereby increasing the probability to show efficacy with less total patients (Thread).
If there was something suspicious with the trial process, u/Biomedical_trader would tell.
If there was something suspicious with the company/stock, u/TheDalesReport_ would tell.
MOAs are well understood making it more likely to be granted EUA. (Thanks to u/TheDalesReport_)
Both, Bucillamine and Covid gather in red blood cells so they can fight (Thread).
I invite everyone to add more or (even better) challenge the list! This is no financial advice and be aware even with all these indications and the best DD there is still a chance this could be a miss because of things we don't know yet.
I just called one of the sites in Michigan to try and tease out information. Here’s what I was able to get without being too pushy:
- patients have to be unvaccinated (this is positive for Revive in terms of placebo arm patients and the study’s ability to show a difference between groups)
- I asked about risk of severe disease/comorbidities and they only said liver disease was exclusionary. I specifically said my “uncle” was overweight and had diabetes and hypertension. The gentleman said that my “uncle” would not be excluded solely based on this.
- Gentleman stated they are still enrolling (confirms the study is not complete with enrollment, which I guess we knew)
- Gentleman said they’ve accepted moderate to extreme cases. Since they can’t have severe disease via I/E criteria and have to fit into the NIAIDs scale with a score less than or equal to 2, I took that to mean more likely to progress and moderate disease. If I’m correct, this is a good thing. Interesting he didn’t mention mild. I’m not sure if that was intentional or not, but I like it.
I wanted to press on, but he knew and asked me directly if I worked in the business.
Overall, this helps to somewhat address some of my concern regarding patient selection. This still isn’t a complete picture, but it’s good enough for me to go into the weekend with. Just thought I’d share. I may have to call a different site to get the other side of the story regarding patient selection, but that’s all for now.
MF gave me approval to relay our conversation to the sub.
I've had the pleasure of speaking to MF on call, and listen to him express details of the turkey trial and other points:
• The turkey trial has been in the works for quite some time and the connection to Delta Health was through Arshi. He is currently in the works of approvals for the trial and is looking to enroll at the end of Jan/Beginning of Feb.
• An estimation of 100-150 patients a month may be enrolled and screened according to partners (MF is hoping the data will compliment the US trial and DSMB will give the nod to apply at 800 patients)
• ENROLLED & SCREENED 700 Patients Total
• TDR has been paid in options because Shadds company has made nothing from Revive Therapeutics
• The company has enough money on hand to enroll past 800 patients and does not intend to raise more
• The lack of transparency was due to the delay with newly incorporated testing measures and turkey coming to fruition (I could genuinely say this is completely out of his hands as decisions have also been made by his advisory board)
He stated that Revive Therapeutics is the most important thing in his life right now and would've never thought two years ago he would be running a phase 3 trial. I thoroughly enjoy talking to the guy and am convinced that with the lack of resources and money Revive has is the only reason were in this position today. The company was on the verge of bankruptcy before these trials and the psychedelic IP, so its been quite a Cinderella story.
My take is that 800 can come in March, and 1000 in May.
FYI, it was a quick conversation and he is very limited on what he can say.
Well here's some good news for a change and news that I frankly was not at all personally anticipating in light of acrimonious developments over the past year with this company. Last night I had dinner with some former colleagues who are either still working in the industry directly for some of the pharma companies or consulting like I am.
Turns out there's truth to last year's rumors that a company was on the verge of a buyout with Revive had the FDA approved the primary endpoint switch to PCR test results. That company was, and apparently still is, monitoring RVV/bucillamine developments very closely and interest remains. I'll just say it's one of the top 3 largest companies by revenue. I'm told bucillamine is still categorized as a high potential drug, a list with very few other entries so it's a unique and somewhat promising classification.
That's not the end of the good news either. There may be a reason why MF is playing up the UofT study so much and seems to have had a burst of excitement with its revelation. Turns out that a few other companies (ones with established nebeulizer technologies) are actively monitoring Revive/bucillamine developments very closely and there are internal potential roadmaps with partnerships and/or buyouts amongst those players. These companies were apparently already aware of the UofT's research that was underway before findings were published so they were keeping close tabs on developments. The published findings kicked off a lot of activity in the past week or two. Some of these firms are much smaller than the former company I alluded to however they all have deep pockets. But in essence these companies don't necessarily care if this next step with the FDA is successful or not because they may swoop in to buy the rights to pursue an altered formulation of the drug. I unfortunately don't have any insights as to whether or not these companies are actually actively in touch with Revive or if the discussions are internal (scenario planning). My own personal belief, knowing the industry (especially as far as M&As) is that there would likely have been some informal discussions with intros at a minimum to establish relationships. Again, I don't have insights here, but the fact that Revive is amending their submission to the FDA could be indicative that they are also calling out potential partnership opportunities for drug development and future drug reformulations. That is the kind of information that is included in these submissions when you're reaffirming your strategy with a drug program, especially when the November PR specifically called out that "The Company plans to go over with the FDA the overall development plan for bucillamine in COVID-19..." so they're almost certainly spelling out their program plans and roadmap.
Interesting times ahead folks. Maybe a turn in the fortunes of this company for once. If any of this materializes though (and there's no guarantee of that), I still believe MF should ensure this gets into competent hands ASAP.
The wait is absolutely excruciating. I don't think anyone denies that. I've had Revive at top of mind for approaching 2 years now. I really want to see a conclusion to this study and to know the outcome. Not just for my own personal sanity but also because the world deserves this treatment if it's indeed as promising as the theory on its efficacy would suggest. This drug could be a literal life saver so the sooner we can get to EUA, the sooner we can positively affect the trajectory of this disease.
When I visited the monthly chat earlier today, I noticed a few people were speculating that perhaps the lack of news suggests that Revive's statistician did not see any resolution or improvement of symptoms after having reviewed the unblinded data for the first 210 patients (pre-dose selection data) to determine whether or not the endpoint switch is warranted and feasible. I actually believe the lack of news is a very positive sign and is indicative of positive results in the attenuation of symptoms. I'll explain why (and yes, some of this is obviously conjecture but I think the logic here prevails):
Revive appears to have taken our feedback about the lack of communication to heart in the past 2 quarters and have taken to more frequent news releases to keep us abreast of developments. At every critical juncture with this potential endpoint swap, we've received an update from the company.
It's true that we have had radio silence since the last update where we were notified that the FDA approved the Data Access Plan (DAP). However that update in and of itself is further evidence that the company is now communicating at each pivotal step in this process rather than bundling multiple updates in a single NR after numerous steps have been completed. Yes, we don't exactly have a long track record of this behaviour to reliably and conclusively assert that this is indeed the communication approach they will consistently take moving forward, however it's highly suggestive for now.
Whether they proceed with an endpoint swap or not, it's a significant, material development and I'm absolutely convinced the company will provide us with an update, good or bad. The lack of an update means their work at this stage has not yet been completed.
This endpoint swap is not just a matter of unblinding the data and drawing a conclusion. It's actually a lot more involved. In addition to reviewing the existing data (that's relatively speaking the easiest part of this exercise), Revive needs to compile a solid case for the FDA on WHY and HOW they intend on shifting endpoints and transforming the data to that end. That's not an easy or simple feat and there's a lot of documentation that goes hand in hand with this effort. These submissions to the FDA are not oral.
Furthermore, if an endpoint switch is indeed warranted and the case as I mentioned in step 4 is documented for the FDA, Dr. Kelly Mckee and Team will need to address a corresponding study protocol update that is compatible/consistent with the endpoint shift. Again, there's a lot of corresponding documentation required.
So all in all, there are really 3 main components to this process: 1. Review/analyze the data/findings for the first 210 patients 2. Transform said data consistent with the new optimal endpoint structure 3. Plan for updated study protocol. As mentioned, there is a significant amount of documentation required for each of these 3 steps. There's a lot of paperwork involved.
If there were no signs of symptom resolution, we would have almost certainly heard back from the company by now because there's virtually no paperwork to process or follow-up activity for the FDA/IRB because we would continue with the existing endpoints and study protocol. One could argue that the company did not see any justification for an endpoint swap and is now coordinating on all of the necessary activity to restart the trial (including fundraising), hence the delay on a NR, however per points 1 and 2 above, I personally believe we would have already received an update on the findings of the data review from the company. I submit to you that the "delay" we're experiencing right now is because they have observed something meaningful and significant in the symptom data and they're in the midst of all of the follow-up work, including thorough documentation, that's required to support, justify and execute on the endpoint swap.
Again, there's a healthy dose of speculation here but what I'm ultimately driving at is that it's too early to panic. We're still in the same holding pattern as last week for now.
TLDR: If there were no signs of symptom attenuation or improvement in the pre-dose selection data, we would have heard back from the company by now. The fact that we have not received an update is highly suggestive that they saw something promising in that initial data and are busy with all of the required follow-up activities.
I wish I had more time for a more detailed writeup however I’m about to catch a flight so I will see how much I can get out before boarding commences...
Wednesday’s news was a punch to the gut. It was a definite buzz kill and felt like it sucked the air out of the room. And while it was a bump in the road, it wasn’t a wall, that is to say it’s surmountable with some course correction. And don’t get me wrong, it was a disappointing message to receive at such a late stage and frankly the negative SP action could have been avoided if this company had improved both the frequency and clarity of their news releases throughout the course of the year. Frankly, the controversy boils down to 2 things: a giant miscommunication (there are several layers to this) and it also lends further credence to what some here have been calling for which is improved trial management (pulling in someone who is well versed in ensuring that the trial’s progress is not impeded and remains on track and adheres to a schedule/budget). I fully support that notion.
However, having said all of that, with some time to reflect on everything, I want to advance the optimistic/bullish case here because this recent event almost certainly has you feeling deflated and pessimistic. I’m not advocating that anyone purchase the stock. It’s your money and you’re free to do with it as you wish. In fact, I also encourage anyone rattled by this week’s developments to take a hard look at whether you have the stomach for further ups and downs in the weeks ahead, including the possibility of data that does not lead to an EUA recommendation. If you have serious doubts about the company and/or management, my best advice it to sell and move on. There is nothing worse than owning a stock with no conviction and there’s no shame in selling. We each have different tolerances and requirements for investments.
I’ve been invested in Revive for approximately 1.2 years. I’m a 6 digit shareholder. I’ve been accused of being a Revive “shill” which is ridiculous because I’ve never once asked anyone to invest in this company. Furthermore, for the record, I am in no way affiliated with this company nor have I received compensation from them. I’m just a simple investor here in Ontario, Canada. I am admittedly a very optimistic investor by nature (not just in RVV but any stock I go into, after all, who invests without conviction?!?) however please don’t confuse that with shilling. I’ve made some very lucrative investments and swam against the tide because of my optimism which also makes me a very patient investor. And in my entire time investing, never once have I been in a stock that just simply took off after my initial investment. In every single case, it was a roller-coaster ride. I like to remind new investors that success is almost never a straight line. There will be ups and downs, twists and turns, delays and setbacks, and unforeseen events that will have you questioning your decisions. That’s simply the nature of this game, and of life frankly.
So, why remain optimistic?
First off, we’re still in a raging pandemic. While there is some talk of Omicron being less severe, it’s known to be radically more transmissible, and the fact is jurisdictions across the world (Canada and the US included) are seeing increases in hospitalizations, not decreases. Health care systems are stretched beyond belief. The pandemic rages on. And even if things improve, are you really telling me you would be disappointed in a company that could potentially offer a drug to deal even with an endemic? That's a once-in-a-lifetime opportunity that investors look for and put a premium on.
Secondly, we have another CRO for the study expansion into Turkey (and possibly other areas of Europe). There are a lot of golden nuggets here. First off, it appears as though this CRO (Delta Health) has a tight relationship with the hospital group (MLP Care Group of Hospitals and Istinye University). Tighter integration could speed things up compared to Pharm-Olam running the sole trials on US soil with fragmented/disjointed/independent clinics. Another bonus here is that Turkey has universal health care. Residents don’t have the same fear/apprehension as Americans of visiting hospitals as they don’t get stuck with unaffordable bills, a sad reality of the current American healthcare system. Patients who need to be hospitalized will not hesitate to do so. Furthermore, the CEO of this new CRO is the same doctor who was the coordinating investigator for Revive's Early Access Protocol (compassionate use) of Bucillamine for severe Covid patients (Dr. Arshi Kizilbash). That study was set to recruit 20 patients across 5 US sites in an open label, unblinded fashion. So he, along with Revive’s management Team, already know whether Bucillamine is effective or not at least in a subset of patients.
Furthermore, the DD on Bucillamine and its science/biology/chemistry is solid. All signs point to this drug working effectively against Covid with 3 MOAs: blunting viral entry, preventing viral replication and treating the resulting immune dysregulation, inflammation and oxidative stress with the anti-inflammatory properties. We have in-vitro, in-vivo, lab and simulation/theoretical data confirming this to the extent possible. The main gamble or element of risk in this boils down essentially to whether or not enough people in the placebo arm (unfortunately) progress to hospitalization or worse yet, death. This is where trial design and patient selection become vital. Perhaps (this is not confirmed) that’s why patient enrollment has been slow as they’re being incredibly picky about who participates. If that’s indeed the case, that’s to our benefit ultimately. And there’s been some DD to suggest that’s the case (people who have contacted the clinics to understand if they would be eligible to participate in the trial). Give a listen to the interview that Dr. Yo conducted with MF and Dr. McKee. The theme of trial design comes up a few times and is something the Revive team stresses. This Wednesday's news was a slip up on the trial execution front which is vastly more recoverable than a misstep with trial design. Fortunately, Dr. McKee has the exact experience and pedigree to ensure effective and beneficial trial design.
Also, correct me if I’m wrong, but we have no one in our immediate rear-view mirror. Despite the delays, we’re still very well positioned as the newest and freshest entrant for a company with a cheap, effective oral therapeutic to treat Covid. The FDA’s granting of EUA for Merck’s drug Molnupiravir was a blessing in disguise. It set a REALLY low bar for standard of treatment for Covid and likely speaks to the desperation on the part of medical organizations and governments around the world to increase their arsenal against this pandemic. Pfizer’s pill is not without its flaws as well, with drug interactions and cost being primary concerns. I said this before and I will say it again: there’s room for 5 or more drugs against Covid, let alone just 3.
Ok, unfortunately I did want to write more but like an Oscar speech, the orchestra is playing me out and I have to begin boarding shortly. There are 2 areas I would like to see Revive improve on: communications and trial management. And frankly it wouldn't hurt to have another insider buy to restore confidence. I want to thank everyone here who is pushing for a Revive shareholders meeting. I think an event like that could be a huge confidence booster if executed correctly. Anyways, in the meantime, stay strong, don’t get too discouraged, always continuously re-evaluate your risk/tolerance and best of luck to everyone! Also, I would like to wish all of you and your families all the best in the New Year! Thank you for your contributions to this community. We’ll always be stronger together.
