Immupharma Share Discussion Threads

[nobbygnome] 21/7/2021 17:59

>> llol

It's all about numbers. I have been involved in discussions with the regulators about post hoc analyses and I can assure you they are always looked on with great scepticism and the smaller the numbers the greater the scepticism. That is an irrefutable fact although that doesn't mean they will always be dismissed. Indeed, in my direct experience the two times a trial was designed following a post hoc analysis (in lupus and CD) both trials ultimately failed dismally. I would be happy to share the name of the two drugs in a PM with s_k.

Even you can't deny that so far I have been correct about Lupuzor.....

[colsmith] 21/7/2021 17:42

Maybe also relevant Lupuzor has to date very little side effect whereas Benlysta in the leaflets has some significant effects. It seems to me that apart from anything else with the extensive testing Lupuzor has undergone over the years one could ask why an emergency approval hasn't been given prior to the formal 2nd P3; maybe the relatively small number of people with this malady don't justify this!; there again perhaps following the formal process is best in all cases.

[1ultimate] 21/7/2021 15:50

Stinger you need some kind of therapy. I hope you get better soon 😂

[lord loads of lolly] 21/7/2021 15:32

nobbygnome - you're sounding a bit like Dominic Cummings to me. Changing the story to suit the emerging facts. Despite the difference in trial numbers, I think sicilian-kan's points remain valid & somewhat disprove your theory. You originally said "From my experience I have never known a post hoc analysis play out when it was properly tested. There is a reason regulators don't accept such data; it is because such data are notoriously unreliable..... Post hoc analyses are fraught with danger." Fair enough. But now you're saying not all post hoc analyses are unreliable. Just the ones IMM does, as its numbers are too small. I fully understand that the lower the trial sample, the less reliable it's likely to be. But that's not quite what you were implying earlier. Still, you've always had an agenda with IMM, despite (apparently) being totally uninvested. Which begs the question, why spend so much time on it, rather than just letting it go & enjoying the good weather? And please don't give us the usual excuse for your obsessive dissing, namely "I really want the company to heed my advice, as I know best". Yeah, right.

[nobbygnome] 21/7/2021 13:05

s_k

As stated in my post I was referring to my own direct experience whilst working in the industry. There were numerous post hoc analyses I was involved in which all lead to failed clinical trials.

The post hoc analysis on benelysta was ever so slightly different than that done with Lupuzor because there were more patients analysed in that post hoc look than in the whole Lupuzor trial. My real point is that basing decisions on post hoc analysis of very small numbers of patients is fraught with danger.

[the stinger] 21/7/2021 12:54

Opened a short here. Expecting 5p soon

[brad44] 21/7/2021 12:37

Nobby only sees and hears what he wants to, and manipulates the mugs that follow him..

[sicilian_kan] 21/7/2021 12:12

Hi Nobby, I take issue with your comment "I have never known a post hoc analysis play out when it was properly tested". You must surely know the Benlysta results [formerly known as Belimumab]!

Benlysta's Phase 2 trial (449 patients) failed, see below [but later passed Phase 3 following post hoc analysis]:

"There was no statistically significant difference between the two groups in attaining either of the primary endpoints. The percentage reduction in SELENA-SLEDAI score from baseline visit was 19.5% in the combined belimumab groups versus 17.2% in the placebo group at 24 weeks, and 27.2% versus 20.6% at week 52, respectively. Furthermore, there was no significant difference in time to first SLE flare over the 52-week course between the combined belimumab and placebo groups (67 versus 83 days, respectively)."

However, they did a post hoc analysis that identified serologically active patients as being the patients that Benlysta worked upon, including the anti-dsDNA patients that Lupuzor is now targeting (see the Lupuzor figures that I gave above - 61.5% active vs 47.3% placebo for anti-dsDNA marker patients. You will see below the conclusion Benysta reached with its post-hoc analysis, and of course, Benlysta's Phase 3 trials were enough to get market approval showing efficacy at 52 weeks in the patients targeted.

"Despite the failure of this phase II study to meet the coprimary endpoints, an extensive post hoc analysis of 321 patients (71.5% of the entire cohort) with serologically active (ANA ≥ 1:80 and/or anti-dsDNA ≥ 30 IU/ml) lupus demonstrated that patients receiving belimumab had significant improvements at 52 weeks in various secondary endpoints: SELENA-SLEDAI score (−28.8% in the combined belimumab group versus −14.2% in the placebo group; p = 0.04); physician’s global assessment (PGA) score (−32.7% versus −10.7%, respectively; p = 0.001); and short form 36 (SF-36) physical component score (+3.0 versus +1.2 points, respectively; p = 0.04)."

and

"The post hoc analysis of patients with serologically active SLE (n = 321) included in the above phase II trial was retrospectively evaluated using the SRI; the response rate was 46% in the belimumab-treated group at week 52 compared with 29% in the placebo group (p = 0.006)."

Then see the comments on the Phase 3 trial that passed:

"All patients were serologically positive, in regards to positive ANA (titer ≥ 1:80) or anti-dsDNA antibody (≥30 IU/ml)."

See

[nobbygnome] 19/7/2021 13:32

From my experience I have never known a post hoc analysis play out when it was properly tested. There is a reason regulators don't accept such data; it is because such data are notoriously unreliable.

Trials are specifically designed and powered to show a certain endpoint and hence post hoc analyses are fraught with danger.

[sicilian_kan] 19/7/2021 13:09

On the Phase 3 numbers, the overall responders were 52.5% active vs 44.6% placebo.

However the Phase 3 responders with anti-dsDNA markers were 61.5% active vs 47.3% placebo.

That % gap (which includes the US patients) was better than Benlysta's subcut results of 60.8% vs 48.5% placebo.

Benlysta has sales based on the last quarter of almost $1bn per year ($975m per year).

It is by no means clear that Immupharma's next P3 will fail. If it repeats its P3 results in anti-dsDNA patients, it will have better subcut results than Benlysta (as well as being massively cheaper to produce). The next trial is fully funded by Avion, Immupharma have excellent royalties in the US and have 100% of the European market. They are, regardless of the likelihood of success, grossly undervalued at present. Hopefully P3 approval will kickstart the re-rating to a less undervalued valuation.

[sicilian_kan] 19/7/2021 12:51

We do not yet know the numbers of patients agreed for the forthcoming P3 trial. Given the amount of money set aside by Avion to pay for the trial ($25m) I would envisage more than the 200 patients in the last P3.

[nobbygnome] 19/7/2021 12:43

Ok I was wrong about that point. However, can you imagine the FDA approving it in the US if the results comes out the same as the post hoc analysis. Of course it won't come out the same because that analysis was done on a low number of patients and therefore has no real validity. That is my real point!

[sicilian_kan] 19/7/2021 12:31

Nobby, fair comment re my recollection of the numbers but the correct numbers only emphasise my point even more! There were 202 patients in the first P3, 72 in the US and 130 in Europe / ROW. This was an FDA approved study, so it is not right to suggest that the FDA wouldn't approval a trial where the majority of patients would not be in the US.

[nobbygnome] 19/7/2021 12:20

>> on target

Fair enough but my point really was that the post hoc analysis was dubious because of the apparent anomaly between Europe (which included Mauritius) and the US.

[nobbygnome] 19/7/2021 12:18

>> s_k

There were only 202 patients in total in the phase III so your numbers can't be correct!

[on target] 19/7/2021 12:16

Not the case these days Nobbygnome.

Have a look at the following:

[sicilian_kan] 19/7/2021 12:03

Immupharma is priced not to fail P3, it is priced not to even enter P3. I am expecting Lupuzor to rerate in the very near future, when FDA approval to start the P3 trial is expected to be announced. See the RNS from 24 June 2021: "The FDA has advised that they do not require a formal face to face meeting and will provide their written response to Avion approximately by the end of July 2021".

[nobbygnome] 19/7/2021 12:02

It's an FDA sanctioned trial so I would hazard a guess the majority would be in the US. The FDA won't approve it unless that is the case

[on target] 19/7/2021 11:57

Where did they say the trial will only include US patients Nobbygnome?

This is from Nov 2019. Have the issued more details on this since?

"· A new optimised international Phase III trial in lupus patients (which is expected to include patients in the US, Europe and elsewhere), is targeted to commence in 2020, following agreement of the trial design between Avion, ImmuPharma and the US Food & Drug Administration ("FDA")."

[nobbygnome] 19/7/2021 11:39

>> colsmith

I will go on record as saying the chances of Lupuzor working in the upcoming trial are minimal. The post hoc analysis on a few patients to come up with the current criteria was dubious to say the least. After all it showed significance in Europe but not in the US. Where is the new trial predominantly going to be run? Oh yes the US.

No doubt the price will go up assuming the trial is approved and progresses into patients but the chance of success at the end is next to zero. Plenty of opportunity for ramping in the interim though as we won't get the result until at least 2024!

All IMHO and NIAI

[the stinger] 19/7/2021 11:22

Obvious multi bagger if trials are a success. Probs 50p min

[colsmith] 19/7/2021 10:55

In terms of Nobby's comment - it passed P2 to give move to P3 and for one version (for want of a better word) it passed a P3 test and it is this version company are targeting in the new P3. So its reasonable to assume it will be successful but of course nothing guaranteed; I guess this view is supported by the US company prepared to foot the bill for P3 to the tune of millions presumably of the opinion that the bet is that it will pass.

[eva_1989] 19/7/2021 09:31

Hi ultimate,

Thanks!

Never sold and no intention to sell until Atleast I doubled it.

So far underwater though.

Happy to wait.

More we will wait, more we will get!

[1ultimate] 17/7/2021 15:41

Eva welcome back. Are you still holding imm??