Hi Kronberg, apologies the late reply, I just got back from a 2 week vacation.
So as we can see from these abstracts and then even moreso from the full presentation on the Protalix website, the data is quite fantastic.
While this interim data is looking at the 6 month time-frame from the switch-over from Replagal to unigal, the fact is that it is incredible to see a reversal of the eGRF decline, which has never been seen at an aggregate level for Fabryzyme or Replagal. Both of these merely slow the continued degradation of eGFR.
The Fabry etiology in kidneys is caused by the GL3 accumulation in the Kidney cells that reduces their ability to filter waster properly. The PRX-102 long half life, activity, and the higher uptake into the kidney cells (also heart and skin cells), means that it would appear unigal is active long enough to not only prevent further accumulation of GL3 in these cells, but also to be able to clear out any remaining GL3 buildup that was happening prior to unigal administration, which could mean that this is enabling previously impacted kidney cells to return some or most of their function. This understanding would be corroborated by the 84% drop in kidney GL3 inclusions after 6 months on unigal, that were seen in the prior phase I/II trial.
In any case, the positive slope that has been demonstrated is clearly superior to current available ERTs and could mean an effective long-term 'curative' medicine to the extent that it appears many of these patients may not have to worry about eGFR decline that is the most common factor that leads them to an earlier death via ESRD. Quite amazing.
I like that they have provided all the individual patients eGFR data points.
Looking at the males only, we can see that of the 9 males presented, 5 saw a reversal of the decline, 1 stabilised, 2 appeared to maintain the same rate of decline from Replagal, and maybe one might have declined, this being patient number 2. However, this decline may be more of a stabilisation, as you can see the final Replagal data point for patient 2 is on par with most of the eGFR values on unigal. One may also look at male patient 16, and assume the trend line to show decline, but when we look at the unigal data points they are all quite consistent on the same level and the patient has had previous Replagal eGFR values far lower than the unigal levels. Note than eGFR can have significant fluctuations and hence why always needs to be compared to the same individuals previous values.
Clearly the females who are originally less effected see the strongest benefit from unigal, where almost all of them see a reversal in the disease state. Patient 12 appearing to have maintenance.
Just a small point against the (I'm sorry to say so) numbskull detractor that is CC Abbott we can see that in the inclusion criteria for all the phase 3 trials for the eGFR is of >40ml/min/1.73^2 for BRIDGE and BALANCE and an even lower >30 for BRIGHT, which is far lower than the 60ml, she was referring to in her pen-ultimate PLX bash as PLX not recruiting 'sicker' patients. These lower levels, thus enabling PLX to recruit very sick patients indeed and still arriving at these stellar results.Though fortunately no-one had a eGFR of less than 50 (49 being the lowest eGFR on Fabryzyme's data) so far at recruitment, and that the one patient Female patient number 6, with the eGFR of 50, saw a 6 month reversal on unigal from a very aggressive downward slope on Replagal.
Essentially, while this is only 6 month data these results are very consistent across all patients and with an unheard of positive eGFR slope at both the aggregate as well as for at least 10 (62.5%) of the 16 patients, and with stabilisation for 3 (18.75%) patients, and potentially an apparent at least non-inferiority for 3 (18.75%) more. Whereas current ERTs showing a clear continuous downward slope on the aggregate.
I would be looking forward to seeing more data soon, on the Anti-Drug anti body response and see if we are getting the similar positive profile as was shown against Fabryzyme. Where there was 0% ADA after one year on unigal, compared to over 70% ADA on Fabryzyme. Also would be nice to see the data on the pain score and frequency of pain medication use change, and Quality of Life.
However the critical thing here is also from the press release that:
"The enzyme has been well tolerated in the study, with all adverse events being transient in nature without sequelae. Most of the patients who are eligible for home care therapy per country regulation are being treated under a home care arrangement in which certain of the scheduled infusions are performed at the patients' home, and the first patient who concluded the study has opted to enroll in a long-term extension study and continues to be treated with PRX-102."
As mentioned earlier I was more excited about this Replagal vs Unigal data as they are both the same alpha isoform. So should be that much easier to see a benefit that when compared to Fabryzyme users who's bodies have been exposed to the beta form for most of their prior treatment.
Just a bit more time to go, and looking forward to any more interim data from either this or the other Phase III.
Also it definitely looks to me that I was right that this uptick was excitement on the interim data, as no OPRX-106 partnership has yet been announced. However let's hope something happens in the coming months.
Just because it's frustrating, one final point on CC Abbott. I find it extremely unprofessional to once again very quickly write up a bashing article based on information collected from abstracts. Any analyst or scientist worth their salt would have waited the additional week to see the full data published before writing such a nonsense article. One key element that really looked like she was fishing for anything was her concern on the fact that the abstract had said "results were statistically significant" but she felt that due to the lack of initially stating a p-value that this somehow couldn't be trusted. If she had just waited the additional few days for the full presentation should would see the p-value was of a very significant 0.015. I can't think of any reason why one would rush to bash other than as mentioned that she is keen to make a buck from gullible SA readers or even worse that she is in fact being paid to do so.
I also don't see any other reason for her continued nonsense and poor analysis for a stock that she consistently and vehemently notes as a sell. Any normal person would stop spending time on a believed strong sell stock. She also doesn't appear to understand or is unwilling to look at the science or actual data either without biased spectacles on. Truly sad.
That said, great work from Protalix thus far.
