One of the things that you alluded to that is so useful for the lead-in study design trial vs. no lead-in is, among other things, assuming adequate statistical powering (e.g., sufficient sample size) we have the opportunity for a much more robust data interpretation of the potential intra-individual value proposition offered by the therapy, in the context of milder vs. severe disease phenotypes.
In addition, we should also have the opportunity for a robust interpretation of this individual value proposition for milder vs. severe disease HemoA phenotypes within the context of achieving specific thresholds of X% of protein expression level.
Indeed, we got a nice initial glimpse of this type of data with the Biomarin phase 3 data pie chart that was posted by the key opinion leader when attending a scientific meeting where that data was presented.
As I understood the KOL's comments posted on 2-4-22 the Biomarin phase 3 104 week Hemophilia A factor XIII protein expression percent ranges/thresholds vs. percent w/ no bleeds data, the 85% bleed free rate at the 5 to < 15% Factor XIII protein & 77% bleed free at Factor XIII protein expression level b/w 3 to < 5% was "possibly less [bleeding] than expected".
But we of course need to see even longer durations, so I'm hopeful for a similar break down of this specific "range of factor XIII protein expression % vs. % bleed free" for Biomarin's phase 3 trial at a further out cut-off point , perhaps in the FDA Adcomm briefing documents/webcast.
So as we know, these Biomarin factor XIII protein expression % vs. % bleed free data up to 104 weeks were on full display for Pfizer to weigh in the context of the factor XIII expression % data & durability data they had already compiled for at least 50% enrollment....and now they are once again progressing full speed ahead. Quite encouraging I'd say.