Why Imbark gets approved
Posted: Wed Sep 19, 2018 3:24 pm
While we all wait for JNJ to $hit or get off the pot, thought I might take a stab at why it looks like even though the MDS data should be significant, MF data will be superior and MF approval will be first and could come sooner than expected. I think the results in Imbark could be very good.
As opposed to conspiracy theories - no the Russians didn’t recruit Trump as an agent 20 years ago, and No, the shorts didn’t hack into the LinkedIn website, I will do my best to just look at the facts. If there is indeed some “approval” lurking, just remember the Imbark trial has three times the patients (roughly 105 vs 35) and has had them fully enrolled for nearly four times as long (roughly 24 month vs 6 months) as compared to Imerge, and therefor much more significant data for the FDA or Eu to gain approval.
I think Median Overall Survival MOS could be 30-36 months for the Imbark 9.4 mg/kg patients, and if so, that could lead to a fairly quick approval as it would triple life expectancy for R/R patients. How do I get that number, it’s just an educated guess, but here goes…
Let’s assume that there are three cohorts in Inbark: 9.4mg/kg, 4.7mg/kg, and those that switched from 4.7 to 9.4. It is possible JNJ and the FDA considers there to be just two, but I think (thinking back to Tefferi and the Mayo multiple cohort data) it has to be considered three, so let’s try that. As we recall from two years ago at the “hold” there were 45 patients in 4.7, 45 patients in 9.4 and 15 new patients in the enrollment pipeline that were allowed to go into the 9.4 cohort. Of the 45 in 4.7, those that were still in the trial, and that wanted to, could move to the higher dose- the crossover group.
So, lets assume 60 patients in 9.4, but we have to make an educated guess in the 4.7 group. Based on the fact that the MDS trial saw many drop, and because the 4.7 patients were not responding, I’m going to guess that maybe only 25 were left, and lets say 15 of those transferred over to 9.4. You can alter the numbers, but I’m probably pretty close, I usually am. So, we have roughly 60 in 9.4, 15 in crossover, 30 in 4.7. Just go with it for now, please.
Now let’s step back and take a look at how long these patients have been treated. A year ago I estimated that the median start date for the 4.7 patients was April 2016 and the median start date for the 9.4 was July of 2016 (later median start for 9.4 because of the 15 late enrolled patients at end of Sept 2016 into 9.4). The average overall start was then June of ’16. Fast forward to Geron’s announcement 19 months later that in January of 2018, yes, NINETEEN MONTHS AFTER JuNE ’16, that Median Overall Survival in all cohorts was at 19 months! None had yet hit MOS.
The preceding info and exercise was done to somewhat prove my numbers are correct, well, because, they usually are So, good job, our numbers match, what does it mean?
Let’s now look at the 4.7 cohort. Why? Because we can work off those numbers in order to estimate what MOS we might see for the 9.4 patients. So, if in January ‘18, the 4.7 patients were in the trial roughly 21 months and the 9.4 patients were in for 18 months, that’s a good thing, not a bad thing as AE so stupidly misunderstood when he thought the 9.4 cohort wasn’t living as long as the 4.7 patients, they simply had not been enrolled as long!
I am going to be conservative and suggest that the “predetermined number of deaths” that happened in April was hitting the middle (median) death in the 4.7 cohort, meaning that the MOS of the 4.7 patients is 24 months, but it certainly could be longer. This is very important. Let’s look at this cohort that hit a MOS of 24 months (it can’t be less than 23, but could certainly be longer).
According to Geron, these 4.7 patients were NOT responding to the drug and that is why the 4.7 group was discontinued in Summer of ’16. These patients got half the drug, they probably dropped out at an alarming rate, therefore getting even less drug because many stopped infusing two years ago. It is possible only 10 or so in the 4.7 group got the drug after the hold! And think of this, those in that group that did respond, those that should possibly live longer and might make the 4.7 MOS metric longer, might well have migrated to the different crossover cohort, thus making the 4.7 MOS numbers worse. What I am trying to say is that this 4.7 cohort should NOT get very good results: They got much less drug, they got far fewer infusions, many stopped taking the drug, those that did respond, probably left that cohort, and yet, AND YET, they STILL MANAGED TO SuRVIVE 24 months!
So, if a group that really had everything going against it, did well at 24 months MOS, what do you think of a cohort that got twice as much drug, more infusions, and was KNOWN to have been responding well would get??? Those results must be better. They must be SIGNIFICANTLY better. I am guessing 30 to 36 months, and possibly, just possibly, more.
That’s my take,
phil
As opposed to conspiracy theories - no the Russians didn’t recruit Trump as an agent 20 years ago, and No, the shorts didn’t hack into the LinkedIn website, I will do my best to just look at the facts. If there is indeed some “approval” lurking, just remember the Imbark trial has three times the patients (roughly 105 vs 35) and has had them fully enrolled for nearly four times as long (roughly 24 month vs 6 months) as compared to Imerge, and therefor much more significant data for the FDA or Eu to gain approval.
I think Median Overall Survival MOS could be 30-36 months for the Imbark 9.4 mg/kg patients, and if so, that could lead to a fairly quick approval as it would triple life expectancy for R/R patients. How do I get that number, it’s just an educated guess, but here goes…
Let’s assume that there are three cohorts in Inbark: 9.4mg/kg, 4.7mg/kg, and those that switched from 4.7 to 9.4. It is possible JNJ and the FDA considers there to be just two, but I think (thinking back to Tefferi and the Mayo multiple cohort data) it has to be considered three, so let’s try that. As we recall from two years ago at the “hold” there were 45 patients in 4.7, 45 patients in 9.4 and 15 new patients in the enrollment pipeline that were allowed to go into the 9.4 cohort. Of the 45 in 4.7, those that were still in the trial, and that wanted to, could move to the higher dose- the crossover group.
So, lets assume 60 patients in 9.4, but we have to make an educated guess in the 4.7 group. Based on the fact that the MDS trial saw many drop, and because the 4.7 patients were not responding, I’m going to guess that maybe only 25 were left, and lets say 15 of those transferred over to 9.4. You can alter the numbers, but I’m probably pretty close, I usually am. So, we have roughly 60 in 9.4, 15 in crossover, 30 in 4.7. Just go with it for now, please.
Now let’s step back and take a look at how long these patients have been treated. A year ago I estimated that the median start date for the 4.7 patients was April 2016 and the median start date for the 9.4 was July of 2016 (later median start for 9.4 because of the 15 late enrolled patients at end of Sept 2016 into 9.4). The average overall start was then June of ’16. Fast forward to Geron’s announcement 19 months later that in January of 2018, yes, NINETEEN MONTHS AFTER JuNE ’16, that Median Overall Survival in all cohorts was at 19 months! None had yet hit MOS.
The preceding info and exercise was done to somewhat prove my numbers are correct, well, because, they usually are So, good job, our numbers match, what does it mean?
Let’s now look at the 4.7 cohort. Why? Because we can work off those numbers in order to estimate what MOS we might see for the 9.4 patients. So, if in January ‘18, the 4.7 patients were in the trial roughly 21 months and the 9.4 patients were in for 18 months, that’s a good thing, not a bad thing as AE so stupidly misunderstood when he thought the 9.4 cohort wasn’t living as long as the 4.7 patients, they simply had not been enrolled as long!
I am going to be conservative and suggest that the “predetermined number of deaths” that happened in April was hitting the middle (median) death in the 4.7 cohort, meaning that the MOS of the 4.7 patients is 24 months, but it certainly could be longer. This is very important. Let’s look at this cohort that hit a MOS of 24 months (it can’t be less than 23, but could certainly be longer).
According to Geron, these 4.7 patients were NOT responding to the drug and that is why the 4.7 group was discontinued in Summer of ’16. These patients got half the drug, they probably dropped out at an alarming rate, therefore getting even less drug because many stopped infusing two years ago. It is possible only 10 or so in the 4.7 group got the drug after the hold! And think of this, those in that group that did respond, those that should possibly live longer and might make the 4.7 MOS metric longer, might well have migrated to the different crossover cohort, thus making the 4.7 MOS numbers worse. What I am trying to say is that this 4.7 cohort should NOT get very good results: They got much less drug, they got far fewer infusions, many stopped taking the drug, those that did respond, probably left that cohort, and yet, AND YET, they STILL MANAGED TO SuRVIVE 24 months!
So, if a group that really had everything going against it, did well at 24 months MOS, what do you think of a cohort that got twice as much drug, more infusions, and was KNOWN to have been responding well would get??? Those results must be better. They must be SIGNIFICANTLY better. I am guessing 30 to 36 months, and possibly, just possibly, more.
That’s my take,
phil