Evgen Pharma Share Discussion Threads

[diamondstar1] 28/9/2019 15:07

Unethical to run a clinical trial with placebo in Metastatic Breast Cancer? Yet, ethical to run a placebo controlled trial in Subarachnoid Haemorrhage? I’m sorry... I don’t buy the unethical argument. The breast cancer study was on top of Standard of Care. How can we interpret the study results, when we don’t have a good yardstick to compare to?

[90005nelson] 28/9/2019 13:28

Primary endpoint timeline is more important than than the secondary endpoint

[90005nelson] 28/9/2019 12:42

SAH trial had a flaw, the statisticians would have picked it up and so would have the clinicians. 40% of patients die within 30 days and for the survivors c.50% will have long-term cognitive impairmentThey would have compelling evidence, by 5th to 18th March 2019 . They had no choice but to delay releasing results.The previous month EVG had printed in February 2019 (Q1) they they would release primary endpoint data in Q2 . There you go

[dave444] 28/9/2019 12:39

Very simply it would be unethical to do so

[90005nelson] 28/9/2019 12:30

Other medications not working, I knew what I meant

[90005nelson] 28/9/2019 12:29

Participants were resistant to other medications

[diamondstar1] 28/9/2019 12:08

Yes, agreeing with your points raised Pennyfalls. New to Evgen, and information gathering from my side. Presumably, the potential bias may be introduced by Investigator knowledge of ultrasound blood flow results, rather than PK results (which should be totally blinded). I fully agree that disclosure of primary and secondary simultaneously is best for the commercial perspective and potential deals. Also, an accurate assessment of neurological/cognitive effects and minimisation of bias - is essential for accurate sample size planning for the Phase 3.
Can I ask a question here - why did Evgen design a Ph 2 trial in breast cancer patients without placebo-control? Seems a bit suboptimal; I fully support the SAH study design.

[pennyfalls] 28/9/2019 11:29

FAO Diamondstar - that’s what I said o) I understand why primary and secondary are released together - and why it could compromise the trial in commercial eyes not to do so.

[90005nelson] 28/9/2019 06:14

Thanks Timbo , from 5th March to the 18th March 2019, it is factually possible, they could have collected 99.26% of all the data for the whole SAH trial. Primary + Secondary. Combined.

[timbo003] 27/9/2019 22:56

"I don't see how the primary endpoint data could effect the secondary endpoint data"

I can. For example, if the investigators have already seen the PK data, they will know exactly which patients will have been treated with active and which patients will have been treated with placebo. If the collection of the cognitive measures is still ongoing, then the investigators will know which patients were on which treatment (i.e. they will be unblinded) during data collection and bias will inevitably creep in, especially given the subjective nature of some of the measurements

[90005nelson] 27/9/2019 18:43

Yeah I think we're getting somewhere near the mark. I believe Evgen Pharma's in informal talks with potential deal or deals. That's why, they decided to combine the release of the primary and secondary endpoint data. I don't believe one would compromise the other as previously stated by people, but it could very well compromise a deal or deals.

[nobbygnome] 27/9/2019 18:12

>> timbo

Completely agree. You would never sign a deal with more data imminent. If that data was negative, the career of whoever championed that deal would be severely compromised.

[90005nelson] 27/9/2019 18:07

A double-blind study is one in which neither the participants nor the experimenters know who is receiving a particular treatment.Primary Endpoints: improved blood flow (ultrasound) associated with the DCI, levels of drug in plasma and cerebral spinal fluid & safety Secondary endpoints: cognitive measures at 3 and 6 monthsStanford–Binet Intelligence Scales: By measuring the memory, reasoning, knowledge, and processing power of the user, this test is able to determine "an individual's overall intelligence, cognitive ability, and detect any cognitive impairment or learning disabilities."I don't see how the primary endpoint data could effect the secondary endpoint data. I don't know if Diederik would agree either.

[diamondstar1] 27/9/2019 15:52

Pennyfalls...
Releasing Primary and Secondary Endpoint data simultaneously makes perfect sense, as Timbo has discussed... because the knowledge of the Primary Endpoint could influence the results of the Secondary Endpoints. Paradoxically, the Secondary Endpoint i.e. neurological recovery will be more important than the Primary (vascular dilation). The reason for Evgen selecting the Primary Endpoint could be the anticipated Pharmacodynamic effect - the study is adequately powered to detect a certain amount of vasodilation by Study Drug. However, the study may not be adequately powered for Secondary Endpoints. Hence, there are few possibilities here in terms of overall results - ideally, the Primary as well as Secondary will be statistically and clinically significant. But an alternative could be the Primary would meet statistical significance but Secondary - show a trend for improvement but not meet statistical significance. Both of these scenarios - would be viewed as positive results, and would support progression to Phase 3. However, there are other results which could be viewed as negative e.g. if Primary Endpoint is positive, but there is no trend for improvement in neurological or cognitive function. Anyway, interesting times ahead for Evgen. I am not a shareholder at the moment, but interested in the MOA of the drug.

[90005nelson] 27/9/2019 13:31

Therefore the RNS 18/03/2019 the advice given below must have been compelling.Following advice from clinicians and statisticians, and in the light of commercial considerations, the Company has decided to announce the primary endpoints (safety, tolerability and measures of blood flow in the brain) and secondary endpoints (relating to cognitive function) at the same time,

[90005nelson] 27/9/2019 13:25

I can prove beyond any doubt, that Evgen Pharma had absolutely no intention of holding back primary endpoint data for the SAH trial in February 2019.

[pennyfalls] 27/9/2019 13:00

Yes Nelson...it's been pushed back to Q4...first they said "early Q4" but now just Q4..
Probably usual Pharma delays.

[90005nelson] 27/9/2019 12:45

Just to be Chrystal clear from Evgen Pharma's own presentation. Read-out of primary and secondary endpoints expected in Q2 2019 and late summer 2019 respectively

[pennyfalls] 27/9/2019 12:03

Hi Nelson...
just musing here, but it sounds like 'transference' - ie you're trying to wrongly conflate two separate study endpoints? Maybe i'm wrong?
So, are you saying because STEM primaries were good that this transfers to SAH?
I could be wrong, but I think that one such endpoint that does transfer appears to be safety of the drug, but otherwise they appear radically different things.

I've also gleaned from reading this board and LSE that some people believe that releasing both endpoints together for "commercial reasons" is de facto proof enough of success, but Timbo's assessment seems to be the right one -
ie, they need to know without mitigation or fear of compromise that the fist endpoint data has not influenced in any way the Secondary endpoint result. And that the final outcome is 'clean'.
Thus , if successful, this is a 100% success without fear of prejudice - but does NOT guide towards a successful result at this stage (in secondary endpoints)

(I allo understand the caveats that , despite being blinded, some Study Staff may have been able to "guess" if the drug is working, especially if remarkable / obvious effects)

[90005nelson] 27/9/2019 11:24

Thanks for your reply, so in that case what do you make of the RNS 25/03/2019 SFX-01 meets primary endpoints in Phase II STEM trial

[timbo003] 27/9/2019 11:09

>>>>Nelson

I doubt if the timings were ever stipulated in the protocol for reporting the primary and secondary outcomes, in my experience the default would be that all results are reported simultaneously. Certainly there was no corresponding notification of any change relating to this at Clintrials.gov


I suspect the directors had at one stage contemplated reporting the results from the primary (blood flow, PK and safety) variables before the other outcomes as they thought it might accelerate negotiations with potential partners and thus mean one less (or a smaller) dilutive placing. However, they then may have concluded (possibly following feedback from potential partners) that by analysing the primary data first, it would detract from the value of the secondary (more clinically relevant) data, so on balance they decided to maximize the potential value and attractiveness of the project at the expense of timings, this was definitely the correct decision IMO.

In my experience, project teams within Big Pharma companies tend to be full of risk adverse, career conscious individuals. If they are tasked with evaluating a project from an outside source and are then told there will be additional data coming along in a couple of months, then in 100% of cases they will defer any decision on whether to pursue the project until they have seen the additional data (Nobby might wish to comment on this point too).Therefore there would be no point handing over half the data set, if there were more data to follow within a month or two.

[90005nelson] 27/9/2019 10:56

I'm invested, but I'm more intrigued than anything. The job role of a statistician and the job role of a clinician, within and towards the end of a trial, giving commercially revelent advice to the BOD. The BOD then decides to change it's agenda, just to maximize commercial value of the dataset. I can only assume that the advice given must have been compelling. Compelling enough for the BOD to act upon this advice given and compelling enough for the BOD to reveal the source from which they made their decision. My own personal opinion, is that this information wasn't directed at shareholders per se but towards potential co-investor partners.

[lovewinshatelosses] 27/9/2019 09:43

So are you bearish or bullish on EVG, Nelson?

[90005nelson] 27/9/2019 08:00

Could you give an example of where the goalpost, in a trial like this, has been moved some 35 months into the above trial. The treatment for participants has remained constant throughout, The study is a randomised, double-blind, parallel-group design comparing SFX-01 (300 mg) taken orally as capsules or as a suspension via a nasogastric tube (NG) twice-daily for up to 28 days versus placebo in 90 patients who have had SAH and present within 48 hours of ictus. Also what could be the revelent commercial only advice, clinicians could give differently at that time in the trial , opposed to at the start or before the trial started? The only thing that has changed is the decision to withhold primary endpoint data for commercial purposes after that threshold has been crossed with a significant (27months worth) of secondary endpoint data.

[pennyfalls] 26/9/2019 18:16

Thanks Timbo - excellent post