A biomarker which has demonstrated 80% (plus) response to a drug - A2-73 is an “interesting” mock trade off for a large trial with NO BIOMARKER RESPONSE.
Let’s assume 1000 patients in a random trial without a predictive biomarker. One of SAVA’s coming ph3:
3 arms is 333 per arm. 666 dosed 333 placebo.
In order to meet a threshold of 80% successful response over placebo, such a trial or trials would need to return 266 improved patients over placebo per arm of 333 or overall 532 combined with correlating dose response and safety. That’s a helluva improbable task.
In addition, AVXL is screening for the right “kind of patients” for the 450 multinational AD trial.
Right “kind of patient” is Sigmar wt gene - we already have been informed thru KEM and proven in previous trials. If we enroll these kinds of patients, our response rate can exceed 80%. (That could be one definition of “wonderful”, imo.)
We are designed with 3 arms, 150 high dose, 150 low dose (total 300 dosed) and 150 placebo.
If we return 80% improvement for each dose, that’s 120 patients per arm. But...we are screening for the right “kind of patients”. Sigmar wt.
The racquet heads on tennis racquets in the 70’s were 55-60 sq in surface area. That’s incredibly tiny compared to racquet heads today - which are almost double. (Eskimo shoes)
The chance of hitting the ball, for club players, is greater with the larger heads. The smaller heads gave amazing control - the entire head was a “sweet spot” - IF you could get your racquet on the ball. The racquet heads got larger due to the use of newer lighter materials used for frames - allowing larger racquets but smaller “sweet spot”.
I once saw an exhibition match where Jimmy Connors beat his opponent (low ranked pro) using a skillet! A kitchen skillet (no trampoline effect and no long handle). All pinpoint control.
SAVA and others may do as many large racquet trials as they like. They will NOT keep 80%+ in play.
If SAVA’s large trial returns 36% improvement (statistically impressive) they can merely equal the total number of patients A2-73 can improve starting from a much smaller pool. In our case, we can reach a statistical significance as impressive as winning a tennis match with a skillet.
Would the public and the FDA ignore this?
Hmmm...
The SAVA smaller shorter ph3 trial is, 600 patients dosed one to one (2 arms) so, 300 dosed and 300 placebo. We have the exact amount dosed in our current trial. I guess 300 is adequate on certain playing fields?
Details are tricky - and can appear scary until broken down. Dr Missling has our trial broken down in the sensible manner and we are screening for the right KIND of patients.
Biomarkers are not tricky and can reduce risk and power up a smaller n trial. Scouts honor!
Watch out for those drop shots!
Bio (marker)
