PROTALIX BIOTHERAPEUTICS, INC. (PLX)

[Spideyboy]

The BRIGHT data is excellent! Also I see CC Abbott is up to her tricks again.

She is again choosing to misinterpret the data cherrypicking the incorrect data point so as to drive her false point home.

One notes that while there are 3 mean data points provided in the latest BRIGHT trial press release, she only chooses 1. And not only that she uses the wrong one, this is of course done on purpose.

CC only discusses this single data point.

"Mean (SE) eGFR slope, at the end of the study, for the overall population, was -2.92 (1.05) mL/min/1.73m2/year indicating stability."

The rest of her article she goes on to discuss why this 'does not' indicate stability. Her data portrayal is once again purposefully misleading. Let me clarify by referring to the more pertinent data for judging the efficacy. But first for full transparency let me provide the 3 mean data points presented in the PLX press release.

"Study outcome measures show that plasma lyso-Gb3 concentrations remained stable during the study with a mean change (±SE) of 3.01 nM (0.94) from baseline (19.36 nM ±3.35) to Week 52 (22.23 ±3.60 nM). Mean absolute eGFR values were stable during the 52-week treatment period, with a mean change from baseline of -1.27 mL/min/1.73 m2(1.39). Mean (SE) eGFR slope, at the end of the study, for the overall population, was -2.92 (1.05) mL/min/1.73m2/year indicating stability."

One other aspect important to note was also mentioned in the press release regards the patients that completed the study.

" The study enrolled 30 adult patients with Fabry disease (24 males and 6 females)"

"All patients who participated in the study received at least one dose of PRX-102, and 29 patients completed the study. Of these 29 patients, 28 received the intended regimen of 2 mg/kg of PRX-102 every four weeks throughout the entire study, while one patient was switched to 1 mg/kg of PRX-102 every two weeks per protocol at the 11th infusion. One patient withdrew from the study after the first infusion due to a traffic accident."

Therefore we see that of the 30 enrolled patients, 1 dropped out due to traffic accident, and 1 moved from the 2mg/kg/ every 4 week BRIGHT regimen to the 1mg/kg every 2 week (e.g. BALANCE regimen) as per study protocol. This switch was at the 11th infusion, which means 10 months were completed on the BRIGHT regimen before switch.

This also means that in fact 28 final patients completed the BRIGHT 52-week regimen.

Back to the data, let us focus on the 2 mean data points that refer to the all important eGFR slope.

1. Mean absolute eGFR values were stable during the 52-week treatment period, with a mean change from baseline of -1.27 mL/min/1.73 m2(1.39)

2. Mean (SE) eGFR slope, at the end of the study, for the overall population, was -2.92 (1.05) mL/min/1.73m2/year


You will clearly see these 2 means are referring to 2 different patient populations.

Data statement 1, is referring to the patient population that underwent the entire 52-week BRIGHT treatment period, e.g. the 28 sample or perhaps 29, if they allow the switch to BALANCE regimen sample in, but I think that would make less sense as this study is about testing the 4 week BRIGHT regimen.

Data statement 2, is referring to the whole overall population of 30 patients. Wherein we clearly know that 1 patient wasn't counted in the study (due to traffic accident) and 1 patient was obviously not responding well to the 4 week regimen and was switched to the 2 week regimen. In the overall study population we are forced to use data from the overall study 30 sample population that did get drug product, hence the contribution of these 2 patients that did not complete the BRIGHT 52 week regimen will clearly bring down the mean.

The only truly important information in this press release if from the patients who did complete the 52 week treatment period, and as we see, the mean change in eGFR was -1.27 mL/min/1.73 m2, with and Standard Error (SE) of 1.39.

An annual drop in eGFR of -1.27ml is similar to normal healthy humans, (which is -1ml per year), and when we consider a normal healthy human is about 100-120 eGFR score, it means that there is enough decline to last almost 100 years of life in a normal human.
"The average drop in the estimated glomerular filtration rate (eGFR) is about 1 cc per minute per 1.73 meters squared per year just on the basis of natural aging. " (FYI 1cc = 1ml) https://www.kidney.org/search-results?solr-keywords=GFR&page=3

Therefore this drop of -1.27ml per year in Fabry patients shows great stability. This mean drop of -1.27ml had a SE of 1.39, which means the distribution of the data was close to the this mean drop of -1.27. This is excellent news for the Fabry population.

Being fully comprehensive and so as not to ignore any information in press release, let us also look at the 3rd type of data point mentioned on "plasma lyso-Gb3 concentrations remained stable during the study with a mean change (±SE) of 3.01 nM (0.94) from baseline (19.36 nM ±3.35) to Week 52 (22.23 ±3.60 nM)"

Here we see that the concentration increase 3.01nM per annum, with an SE of 0.94, which means the results for the patients were all very similar again.

Classical Fabry Females have a plasma lyso-Gb3 of about 7nM, but the much more affected Classical Fabry Males (remember Fabry is an X-linked disease which affects men more much more seriously), have a mean plasm lyso-Gb3 of about 100nM. Please feel free to refer to the data generated by Sanofi (remember they make Fabrazyme) from 154 Dutch Fabry disease patients. http://www.sanofimedicalaffairs.com/rarediseases/images/resources/SGUSMAFD18110671avFinal10.pdf

Thus have a mean increase of 3nM per year is a very low increase in these milder BRIGHT 2mg/kg/ 4week regimen patients.

Again this is excellent news for Fabry patients.

This makes it very clear why "After completion of the study, all patients enrolled in an extension study"


Thank you for your time, and looking forward to hoped for good news next week with the Topline BALANCE read out.

If anyone wishes to repost this analysis or link this anywhere, please feel free to do so.

Best Spidey.