This is all great news,
In addition to the repeating of the BRIDGE topline data that we saw before, which essential brought the rate of kidney degradation from a horrendous -5/-6 slope despite being on ERT, into normal range of a healthy person, we also have nice data on the Anti-Dug-Antibodies/immunogenicity as well as the GB3 levels.
Immunogenicity:
"four out of 20 patients (20%) developed persistent antidrug antibodies (ADA) over the course of the study, of which two had neutralizing activity."
So 20% showed ADAs on pegunigalsidase, vs known 74% showing ADA on Fabryzyme. Not only that staggering drop in ADA, but also pegunigalisase's 20% is consistent with its Phase I/II Trial (Schiffman presentation on PLX website) from 24th November 2017), which showed 19% ADAs. Consistency is always nice to see.
Not only that but of the 4 that showed ADA, only 2 of these had neutralising activity, so 10% of the total sample. This compares to the Phase I/II data which showed 2 of the 3 ADA patients has neutalising activity or 12.5% of the Phase I/II total same of 16 patients. So this too is consistent or even lower/better.
This would position pegunigalsidase to be much less 'neutalised'/attacked by the body's immune system leaving the enzyme to carry out its job, with is 80x longer half life too.
Lyso-GB3:
Both males and females saw a drop of 30-32% of the existing levels they had despite already being on Replagal.
One can note looking at the graphical BRIDGE interim analysis data from the Linhart presentation of the 10th Feb 2020 under the presentation section of the Protalix website, that there are a small number of male patients with extraordinarily high baseline lyso-GB3 (up to 3x higher than the already high males levels), which skews the mean in the male cohort. When looking logically at the baseline Lyso-GB3, it would be somewhere around the level of 40nM in Males, which would be lower than the skewed higher 51.81nM mean presented. The baseline variation is less in the less effected females so the interim female baseline is about 14-15nM and the final baseline is 13.81nM as per the recent PR, which makes sense, again consistency.
One can also see in the interim data that, when removing the exceptionally high skewed data points, for the males after 12 months they have a lyso-GB3 of about 20nM, and the females of about 8nM.
We can see then that the final data produced the same 12month result, 19.55nM in males and even better 4.57nM in females. One should also note that the ability for pegunigalsidase final data to bring down the mean to the 20nM mark without removing the skewed higher data point, as I just did, would I believe show the particular efficacy overall in males, while we also see a drop in females even though their baseline is already significantly lower than the males.
This removing the skewed data points, it would generally show, pegunigalsidase would be reducing the males Lyso-GB3 from approx 40nM down by 19.55 or by 49%, while the female analysis with less skewed data, can be taken directly at that presented below.
Of course PLX cannot removed skewed data-points as I just did, hence the mean male baseline value is higher and the apparent mean reduction lower than my approximate analysis here.
Despite this, the data is indeed very very nice to see and I feel does bode well.
Now we just need the FDA to visit the manufacturing sites. I do hope they can for all patients and investors alike. This product thus far it appears, will quite literally give patients many many more years to live a healthy life vis mitigating Fabry disease compared to current ERTs.
