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Thank-you Joey!
Here are the minimum requirements for activ-2 progression.
Virology:
The virology-based graduation guideline for an investigational agent to be eligible for phase III evaluation will be evidence of any one of the following:
1. Higher absolute proportion of participants with SARS-CoV-2 below the assay LLoQ in NP swabs by at least 20% at one or more of the scheduled in-person measurement times (e.g., 60% for placebo and 80% for investigational agent at day 7) as compared to placebo (i.e., X in the probability statement above is an absolute 20% increase for this outcome); or
2. A decrease in median SARS-CoV-2 RNA levels in NP swabs of at least 0.5 log10 copies/mL at one or more of the scheduled in-person measurement times as compared to placebo (i.e., X in the probability statement above is 0.5 log10 copies/mL) (measurements after day 7 are not considered as a majority of participants are expected to be undetectable after day 7); or
3. A relative reduction in median area under the curve measure (AUC) of SARS-CoV-2 RNA levels in NP swabs through study day 7 of at least 20%, as compared to placebo (i.e., X in the probability statement above is a relative 20% reduction).
The absolute difference of 20% in (1) and the 0.5 log10 copies/mL difference in (2) were surpassed in a comparison of monoclonal antibody treatments in trials for persons with COVID-19 [16, 17, 24]. The threshold used in (3) also seems
achievable based on the same studies, although the AUC outcome was not formally evaluated in those trials.
Clinical:
The clinical/symptom-based graduation guideline for an investigational agent to be eligible for phase III evaluation will be a relative reduction of at least 40% in the proportion of participants with either moderate or severe symptoms reported at day 7 (of the targeted symptoms in the participant diary) or have been hospitalized or died on or before Day 7 (i.e., X in the probability statement is a relative 40% reduction).
Safety:
Graduation to phase III will also depend on an acceptable safety profile, as determined by the DSMB. This decision will largely be based on differences in the frequency of Grade 3 and 4 AEs between participants receiving the investigational agent and those receiving placebo.
Stu, Stu! lol Logic (yes logic) tells you that if this was dud or anywhere near a dud in P2 it would not progress, they would not refer to other previous data sets SNG have used or promoted it with, as that is the whole point of their US trial to prove the older data released is correct and stacks up. The trial is for specific reasons as set out (that is why it is called a clinical trial and has to be pre-determined with data read outs to progress). You are alluding to that they have changed the data set requirement end points at this stage to progress it for other reasons/purposes (Never happen) Just to accommadate SNG progressing on the trial. You would have to start a completely new trial with a complete changed data set agreed for patient use if that were the case, whether safe or not (you would need to get the new data end points signed off and detail specific new testing criteria).
I have to say the point of view they progressed based on maybe older data (un-witnessed by them is a bit far fetched considering you are basically saying it maybe did not meet their trial requirements) - Not too sure about that lol
What you are saying is ludicrous under trial conditions.
You are repeating the same question as earlier to which I gave a lengthy reply based on the protocol. But more specifically, when you say "maybe that’s why Synairgen have chosen to not say a single word on P2 efficacy where others have " this cannot be the case as Synairgen have clearly said they have not received any data of the trial. So it can't be that they are deliberately not commenting on exactly how effective it was given they don't know this themselves. All they (and we) know is (as I explained at length) that the DSMB recommended that it proceed, which must mean there is sufficient efficacy data in the phase 2 trial itself for it to proceed.
Read version 7 of the activ-2 protocol and it tells you what the progression criteria is to reach P3.
…All valid points of which I’m aware.
For argument sake, let’s say efficacy was at best marginal in P2.
My question is in that situation could we progress to P3 given additional consideration to other efficacy data sets and knowing safety’s fine? I think yes and just maybe that’s why Synairgen have chosen to not say a single word on P2 efficacy where others have .
“Pre-defined safety and efficacy criteria, including
assessments of antiviral activity and clinical efficacy”
I didn’t say detailed just that it’s reported. See above.
We haven’t done the same ?
Stu485, you ask:
"Looking at the BRii news release for progression from Active P2 to P3, there is content regarding efficacy.Why do you think in stark contrast Synairgen makes no reference to efficacy ?
Is it possible in the Synairgen case, consideration was made on trial safety and supported by the "growing evidence" referenced in the Synairgen RNS ,of likely efficacy from other studies trials but not specifically Active ?"
I think the answer can be found in Synairgen's RNS, which was much briefer than BRII's release. They said ".... the external data safety monitoring board (DSMB) of the ACTIV-2 study has recommended that SNG001 advance into Phase 3 ...." In the protocol of Activ-2 recently published it's clear that there is a Trial Oversight Commitee (TOC) who make the decisions, based on recommendations from the data safety monitoring board (DSMB). In the "regimen" of the "schema" (page 15) which sets out the general overview of the study, it says "Investigational agents will be included in phase III evaluation based on agent entry criteria for phase III as outlined in the protocol (or by TOC approval based on data available outside of ACTIV-2)." Thus there are two options for progression to phase 3, the first is " based on agent entry criteria for phase III as outlined in the protocol ". The second possibility is that the TOC approves it "based on data available outside of ACTIV-2". Under the second scenario, it seems that it is the TOC who decides without reference to the DSMB, as the DSMB are only there to assess the data from the Activ-2 trial itself.
This is further clarified In the main body of the protocol on page 29-30 which says "The DSMB will review unblinded data and make recommendations to NIAID (as trial sponsor) and to the TOC, indicating whether graduation criteria have been
met (see below for criteria). The recommendation for an agent to enter phase III evaluation will be made by the TOC in discussion with the company...." and then "The TOC may recommend an agent move directly into phase III, without evaluation in phase II in ACTIV-2, if there is sufficient safety and efficacy data supporting phase III evaluation available from outside of the trial. These agents will not undergo graduation analyses."
Since Synairgen stated in their RNS that it is the DSMB who recommended progression to phase 3, it seems clear that there was safety and efficacy seen in the Activ-2 trial itself, as then explained under "Criteria for Graduation of an Agent from Phase II to Phase III" - "Graduation of an investigational agent from phase II to phase III evaluation will be based on there being a desired level of evidence of an effect of an investigational agent versus placebo on one or more virologic and clinical outcome measures, as well as safety...."
The only caveat is that the efficacy required for progression is EITHER a lower level of the virus detected in samples taken, OR an improvement in symptoms, we cannot be sure wh
Doc83,
Acacia Research:
Just for old times sake
https://www.thisismoney.co.uk/money/markets/article-9271871/Woodford-fire-new-role-fund-bought-assets.html
And, as many will remember, one of Woodford’s ‘knock down stocks’ acquired, was good old Synairgen.
PMJH,
Looking at the BRii news release for progression from Active P2 to P3, there is content regarding efficacy.Why do you think in stark contrast Synairgen makes no reference to efficacy ?
Is it possible in the Synairgen case, consideration was made on trial safety and supported by the "growing evidence" referenced in the Synairgen RNS ,of likely efficacy from other studies trials but not specifically Active ?
Re:PR
There was an article in the express hailing the ‘wonder drug’ after Activ-2 , a proactive interview, plenty on social media since their appointment. I don’t see any of the other companies I am invested in promoting changes in shareholding’s of ii’s.....
The PR team will earn their keep when P3 data is released.
I own just short of 0.00197% of Synairgen, how do I do a TR1? LOL
One I’m not familiar with…
Acacia Research - 1.59%
Holders right down to a few shares on there. Of course, most buy through the likes of HL, FIL etc.
Matml74,
Tikvah - 4,845,074 / 2.41%
Venrock - 0
Thank you , phase 3 continuation of phase 2 . Top man
Well polygon and co , seem to have a game plan , polar and co must be concerned,
the SP is your normal Aim peaks and troughs, it would be nice to know US data
Causing a lot of speculation, I bought at 175 so have enjoyed the last few weeks.
Just hope we are not short changed , RM he said this drug works.
My last rant for today,
EMA = Europe Mediscience Science Awards 2021 just in case you have forgotten
Johncott
I was thinking the same , but I think The EMA Awards are imminent around the 16 Nov perhaps he can blow the trumpet then together with other pending news
I thought SGN had employed PR media manager / Director
. No comment up to now
Doc, Thanks for the update on LL. Last I saw Venrock and Tikveah still had holdings. Be interested to know their positions.
I'd expect Polygon to show their hands prior to P3, not after. Something's got them moving IMO.
Matterhorn good post. Correct I think paragon are racing against the clock to grab shares at a lowish entry price before gradual uptick in the SP which maybe forthcoming due to events outside their direct control. And importantly if there is an unforeseen early bidder. I was thinking today that some bidders will wait for phase 3 readout, so if I were the more needy patent challenged pharma I would go early at this and perhaps reduce those willing to bid with me by response. That's my take. I know GSK were very clever with their VIIV partnership deal and value segmentation so it's not put of the question there is a deal being cooked early by one of the bigger players. I'm not trying to ramp just sharing thoughts. I don't need to ramp your all sold anyway on this stock.
Much appreciated Matml and Doc.
What's the smallest percentage of holding the Bloomberg terminal shows.....as in does it show all holdings above 0.5% or 1% or?
Becontraian,
The difference was they weren’t rns’ing every one percent. The first rns was 5% the second 10%, 2/3rds of their holding! Whilst it feels like they have ramped up recently that is due to frequency of holding updates. They have also had 2 pivotal rns’s, 30th sept results (and perceived delay) and Activ 2 promotion. These two events they played perfectly to add a further to their holding by creating volatility and the concerns of holders with less conviction or those who had held since last years placing and wanted out with a small profit.
IMO they think there is a significant uplift in SP coming on a positive P3 result and I agree.
I have a Bloomberg terminal. Leonard Licht has 4,419,975 shares /2.2%.