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Posted On: 03/07/2019 7:34:53 PM
Post# of 154723
My take on CD03 Update
Poster https://content.equisolve.net/_0d78061067963e...KD1_VM.pdf
+++
What were the Mono PE goals? CD03 https://clinicaltrials.gov/ct2/show/NCT028599...amp;rank=3
The very last Investor presentation, which spells out Monotherapy PE is from 03/01/2018.
300 pts, PE responder rate > 70%, SE achieved (may return to HAART).
+++
Poster data included for 700mg Group:
36 ongoing + 6 failure + 1 early-termination = 43 pts, or
36 ongoing + 7 failure = 43 pts.
The 100% 700mg performance for timepoint period 12-24 weeks
is misleading for overall efficacy,
they capped the 0-12 weeks 6/43 VL failure (14%) already and one early termination.
This gives us a maximum possible responder rate of 36/43 = 83.72% if all 36 ongoing patients would pass.
Note that the 525mg group of 8 completed + 62 ongoing (rest failure/terminated) has a maximum possible responder rate of 70/115 = 60.87%. Hence this group has already failed the PE!
Even worse the 350mg group: 57/229 = 24.89%.
Note that all ongoing pts would still need to pass to achieve given maximum responder rate.
+++
Now let's recapitulate some 700mg data:
Investor presentation slides from 11/08/18 (SHM) using the 23 pts 700mg rescue arm (failed 525mg rescue arm, dose escalation) said ~52% suppressed and 22% failures.
Investor presentation slides from 01/01/19 said ~90% of 700mg pts in first 1-16 weeks, w/o giving pts count.
Investor presentation slides from 2/11/19 said 100% of 22 700mg pts in first 10 weeks. So 6 of the additional patients had a VL rebound/failure.
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How many more can fail?
29% failure for 71% responder rate of 43 pts
-> Limit 28% 12 pts failure, 72% 31 pts responder.
7 pts already failed (1 + 6), so we have a free buffer of 5 pts.
It is tight, but gladly all 700mg failures occurred in the 0-12 weeks so far!
We still need all ongoing 36 patients to complete the last timeslot 24-48 weeks.
+++
+++
Safety wise, we had 30 SAE incidents in total of 387 pts or 7.75%, where it is unknown whether these were definitely or probably related to PRO 140.
This is probably OK, but have no details about the nature of the SAEs yet.
+++
+++
Bottom line is (only) 700mg is good enough to pass PE safely.
They say they want to enroll additional 200 pts across all 3 dosage groups, which IMHO is a waste of time.
Why not simply enroll them to 700mg only?
(See: Methods & Materials)
This will take some more time to conclude and only thereafter will we have negotiations for the pivotal trial.
While 700mg for mono looks good, I would like to see us concentrating just on that group and dismiss the lower dosage to safe time & resources.
(courtesy copy from my orig post on ihub)
Poster https://content.equisolve.net/_0d78061067963e...KD1_VM.pdf
+++
What were the Mono PE goals? CD03 https://clinicaltrials.gov/ct2/show/NCT028599...amp;rank=3
The very last Investor presentation, which spells out Monotherapy PE is from 03/01/2018.
300 pts, PE responder rate > 70%, SE achieved (may return to HAART).
+++
Poster data included for 700mg Group:
36 ongoing + 6 failure + 1 early-termination = 43 pts, or
36 ongoing + 7 failure = 43 pts.
The 100% 700mg performance for timepoint period 12-24 weeks
is misleading for overall efficacy,
they capped the 0-12 weeks 6/43 VL failure (14%) already and one early termination.
This gives us a maximum possible responder rate of 36/43 = 83.72% if all 36 ongoing patients would pass.
Note that the 525mg group of 8 completed + 62 ongoing (rest failure/terminated) has a maximum possible responder rate of 70/115 = 60.87%. Hence this group has already failed the PE!
Even worse the 350mg group: 57/229 = 24.89%.
Note that all ongoing pts would still need to pass to achieve given maximum responder rate.
+++
Now let's recapitulate some 700mg data:
Investor presentation slides from 11/08/18 (SHM) using the 23 pts 700mg rescue arm (failed 525mg rescue arm, dose escalation) said ~52% suppressed and 22% failures.
Investor presentation slides from 01/01/19 said ~90% of 700mg pts in first 1-16 weeks, w/o giving pts count.
Investor presentation slides from 2/11/19 said 100% of 22 700mg pts in first 10 weeks. So 6 of the additional patients had a VL rebound/failure.
+++
How many more can fail?
29% failure for 71% responder rate of 43 pts
-> Limit 28% 12 pts failure, 72% 31 pts responder.
7 pts already failed (1 + 6), so we have a free buffer of 5 pts.
It is tight, but gladly all 700mg failures occurred in the 0-12 weeks so far!
We still need all ongoing 36 patients to complete the last timeslot 24-48 weeks.
+++
+++
Safety wise, we had 30 SAE incidents in total of 387 pts or 7.75%, where it is unknown whether these were definitely or probably related to PRO 140.
This is probably OK, but have no details about the nature of the SAEs yet.
+++
+++
Bottom line is (only) 700mg is good enough to pass PE safely.
They say they want to enroll additional 200 pts across all 3 dosage groups, which IMHO is a waste of time.
Why not simply enroll them to 700mg only?
(See: Methods & Materials)
This will take some more time to conclude and only thereafter will we have negotiations for the pivotal trial.
While 700mg for mono looks good, I would like to see us concentrating just on that group and dismiss the lower dosage to safe time & resources.
(courtesy copy from my orig post on ihub)
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