Random musings on things I don’t understand

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biopearl123
Posts: 1665
Joined: Fri Jul 20, 2018 5:13 pm

Random musings on things I don’t understand

Post by biopearl123 » Mon Jan 21, 2019 1:41 am

Buckminster Fuller said something to the effect that there is nothing in a caterpillar that tells you it is going to become a butterfly. At MOS of 29.9 months roughly half of the high dose group are alive. But only 7 patients remain on drug in this study (6 high dose, 1 low dose) so many patients came off drug. Looking at the adverse cellular events that reversed with dose modification we really don’t know why so many patients appear to have come off drug. The question I pose is if these patients could have known they would live longer (and they couldn’t since the data was not finalized) would they have come off drug? Were they still caterpillars? Here’s another question. It looks like it takes control of 3% of shares to petition for a position on the board. I don’t have that but it has been suggested in previous threads perhaps we could take a poll to see if a group might have the requisite number of shares to get a name on the ballot. By my reckoning I have .25% so clearly we need some big hitters. Can we come up with another 2.75%? Can we get a shareholder on the ballot. Regards, bp

karagozoglu12345
Posts: 61
Joined: Wed Oct 03, 2018 12:48 am

Re: Random musings on things I don’t understand

Post by karagozoglu12345 » Mon Jan 21, 2019 5:56 pm

Biopearl: I did not know that 7 patients remaining on the trial. As you said if the drug prolongs life significantly why has many patients dropped out? Is it possible that symptoms of the illness (that Imet does not treat well) were unberable as the reason for dropping out? Did the patients use another drug for the symptoms while on Imet? I hope they collected data as to the reasons why the patients did not remain in the trial. This to me is an alarming issue and may even be one of the reasons J&J walked. Also, extension of this trial for another year is confusing. Is MOS data not sufficiently long for approval? What if MOS data continues to improve, will it have a decisive effect given such a small sample?

biopearl123
Posts: 1665
Joined: Fri Jul 20, 2018 5:13 pm

Re: Random musings on things I don’t understand

Post by biopearl123 » Mon Jan 21, 2019 7:23 pm

Kara, it appears that 7 patients remained on trial as of the April data eval at 24 weeks. The investigators and the company do not appear to have shared how many patients remained on drug if any at the time of the Oct MOS determination. Yet another glaring omission of pertinent data. bp

biopearl123
Posts: 1665
Joined: Fri Jul 20, 2018 5:13 pm

Re: Random musings on things I don’t understand

Post by biopearl123 » Mon Jan 21, 2019 11:01 pm

Almost half of patients (47%) stoped study drug because of 1. Lack of efficacy, 2. Physician decision 3. Patient decision. As I continue to think more about this I return to Buckminster Fuller. Almost half of the patients who withdrew or were withdrawn could not know they might be butterflies. Optimism is its own disease. bp

huntingonthebluffs
Posts: 246
Joined: Wed Feb 24, 2016 12:00 am

Re: Random musings on things I don’t understand

Post by huntingonthebluffs » Tue Jan 22, 2019 6:30 pm

Maybe I should be, but I’m not alarmed on why there are only 7 still in treatment in the MF CT. While yes, I don’t believe there is much room for compassion in CTs, it does seem to me it was probably arbitrary, given the strict nature of CTs and the FDA’s regulations/guidelines, etc. Possibly the primary endpoints (both) had to be met to continue on with treatment during extension periods following the official clinical cutoff on April 26, 2018. Anything less might be considered lack of efficacy. Does anyone know or have other CT experience on this to answer?

I know only 6 show up with >= 35% SVR at 24 weeks but wouldn’t be a stretch at all to get to 7 as the median duration of treatment was 26.9 weeks and 21 patients were >= 50% reduction in Total Symptom Score at 24 weeks so one more getting to 35% SVR seems plausible to me. Either way, I don’t believe there is anything subversive in the results we have been provided and the corporate and medical sentiment seems to be robustly positive. Also, I might recall that that the FDA apparently required Dr. Tefferi to only allow patients to remain in the Phase 1 CT if they had a CR/PR response, just having a CI wasn’t justification to remain in the study.

I do however continue to be alarmed that the FDA regulations / guidelines do not require treatment to continue if the patient’s disease has stabilized even improved, especially if they have achieved a state where the disease is not progressing given the LE of these patients without treatment options. Even more evidence of this misguided approach is that Dr. M. commented something to the effect that they could have likely achieved significantly better results if they had treated the patients through their various issues by managing the dosage, treatment interval, etc. This is not in vitro test tube or petri dish testing that is at stake here! This clearly seems to be an area where the FDA should also consider modifying their controls where LE is very limited and potential outcomes would likely improve given continued treatment. We know we would find many more caterpillars that could become butterflies.

As far as contributing share ownership to our activism, I definitely consider you a “big hitter”! I’m not but would gladly contribute what I have to the cause (.05%), given you are the nominee. However, assuming there are a dozen in your class of ownership, you would have what is needed to nominate.

sandshark
Posts: 6
Joined: Fri Jul 27, 2018 7:51 am

Re: Random musings on things I don’t understand

Post by sandshark » Wed Jan 23, 2019 10:22 am

For what it's worth count my 0,0134% in :(

bucbeard
Posts: 80
Joined: Wed Jul 25, 2018 12:30 am

Re: Random musings on things I don’t understand

Post by bucbeard » Wed Jan 23, 2019 7:17 pm

more great conversation, thanks all!

count my .023% shares in BP

karagozoglu12345
Posts: 61
Joined: Wed Oct 03, 2018 12:48 am

Re: Random musings on things I don’t understand

Post by karagozoglu12345 » Wed Jan 23, 2019 10:55 pm

I think we longs tend to have thoughts that often reflect confirmation bias. Perhaps, there is value in playing devils advocate from time to time to put issues in a balanced and realistic perspective.
Considering all of the facts that we know this far, I tend to think best we can hope in MF story is FDA endorsement for Phase 3. But, even this likelihood is not so straightforward because of the following issues:
Assuming FDA has policy to signal a green light for Phase 3 predicates Phase 2 was successful. How can it be logical otherwise?
Imbark Phase 2 is messy at best for a number of reasons:
A shift of end points from symptom related ones to MOS may be problematic. The evidence for the validity of MOS as an endpoint appears to be compelling but in some respects murky as well. In this vein, unanswered questions (to my knowledge) are: If Imet treats the underlying cause of disease( i.e., apoptosis of cancer cells), ala Tefferi trial and his claim as such, then why do the symptoms ( e.g., spleen size etc.) largely remain in Phase 2 CT? If there is a lag effect in symptomatic relief, do we have evidence from CT's to demonstrate this ( I believe we don't have such evidence and the trial may be extended for another year to collect such evidence)?; Since we do not know the specific pattern of reasoning why 47% of patients left the trial, it may not be far fetched to assume that the trial was not successful for them most likely due to their lingering symptoms. And, given this group of patients are R/R, even if Imet indeed prolongs life, would patients be willing to try Imet while knowing they will continue to be very sick? And, this group of patients no longer benefitted from the only available drug Jakafi as a precondition to enroll in Imbark, what kind of additional drug intervention can help these patients live longer lives without feeling very sick for the rest of their lives? I believe we don't have answer to this question either. Perhaps, jakafi may work again if tried simultaneously while on Imet but to my knowledge this alternative has not been tried yet.

Count on my 0.06%.

ashah
Posts: 60
Joined: Wed Jan 09, 2019 1:32 pm

Re: Random musings on things I don’t understand

Post by ashah » Thu Jan 24, 2019 4:26 am

Count my 114K share in too...

jingledsassy
Posts: 53
Joined: Wed Jul 13, 2016 4:15 pm

Re: Random musings on things I don’t understand

Post by jingledsassy » Thu Jan 24, 2019 4:14 pm

you can add my 38k shares also...

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