Hodge, I think the best case scenario should be given as a range.
Just to be clear….we are talking about Direct. Let's also hope, in the meantime, if all goes well, it is possible the compassionate use programs around the world will be expanded to include Direct.
Let's assume the final primary results of the phase I/II unblinded study come out between September 1, 2014 and November 30, 2014. (Note: since there is no control or cross-over arm, it will not be concluded earlier than enrollment, treatment and response allow for.)
If the results are what we hope for, there will be significant tumor shrinkage and/or eradication with signs of immunity in 80-100% of patients.
If memory serves me correctly, Direct also has orphan status and fast-track status (or it will), and because the next stage trial -- whether that is classed as a 2b or 3 -- will almost certainly use tumor regression as the primary endpoint, the route to final approval would be be sped up enormously -- again, if all goes well.
Here is another thing, if the results are really good as we enter into spring and summer, NWBO can start phase 2b screening and enrollment before final primary results are 'official.' There is precedent for this.
The phase 2b or 3 trial design will be paramount in determining the speed at which it moves. Assuming strong results from phase I/II, even though the the size of the imagined pivotal trial may be large for an orphan drug -- let's ballpark 600 -- nonetheless, the enrollment rate will be faster than any prior cancer trial (IMHO).
So let's project the pivotal trial for Direct is announced September 1, 2014. There will be no start time bottleneck (as was the case in phase I) because the drug has already been used in a first in human study. Thus, sponsor trial execution, number of clinics and doctors will be the only rate limiting factor other than response time.
The responses for Direct are blindingly fast for tumor reduction. Here is the part that many of us forget from time-to-time. In most trials, we are waiting for a certain number of negative events to occur before we take an interim look, but with tumor reduction as the primary endpoint, we are waiting for positive events to occur. In this case, if those positive events are to occur, they will happen within days to weeks.
Let's project enrollment (in our example pivotal trial) is full within 6 months….due to incredible demand, and because we have and will have so many clinics available between the U.S. and Europe to handle the screening, enrollment and treatment.
Let's say the 1st interim look is at 6 months from enrollment initiation.
60 Days for analysis.
Next, in the best case scenario, they unblind the study.
Linda states it can take about a year for FDA approval following a successful pivotal trial.
However, here again, we can have a better case scenario. Let's say Linda gets an NDA application to the FDA 90 days after the phase IIB or 3 results come in.
Normally the FDA would have a decision within 6-9 months, however, because this treatment is for inoperable terminal cancer patients (the highest immediate need possible), The FDA can shorten their decision window to 60 days.
Hopefully NWBO has ramped up production capacity so that there is little to no delay in launch.
If all goes very well, In my opinion the earliest one might be able to get DCVAX-Direct commercially prescribed is somewhere between October 1, 2015 - December 30, 2015. Prior to that, one would need to try and get into any available trial or compassionate use program (when/if those are made available).
