PROTALIX BIOTHERAPEUTICS, INC. (PLX)

[Spideyboy]

I had a look through the new FDA draft guidance on "Slowly Progressive, Low-Prevalence Rare Diseases with Substrate Deposition That Results from Single Enzyme Defects" that was mentioned by Moshe in the last earning call and with relevance to application for Accelerated Approval based on the already over 100 patients data on PRX-102.

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM614641.pdf


Regarding this, PRX-102 appears to meet numerous criteria that would allow Accelerated Approval designation.

- "When the pathophysiology of a disease is well understood and the mechanism of action of the drug/biologic is well characterized, specific drug-induced substrate reduction in relevant tissue(s) can have a reasonable likelihood of predicting clinical effectiveness. In such a case, a clear demonstration in clinical trial(s) that an exogenously administered enzyme reaches the tissue of interest and results in substrate reduction can be seen as reasonably likely to predict clinical benefit and can serve as the basis for accelerated approval"

Fabry pathophysiology is well understood, PRX-102 as a pegylated from of Replagal and isoform of Fabryzyme is well characterised, substrate reduction (GB3) has been noted with significant decrease in the the relevant tissues (Kidney, Heart, Liver), PRX-102 has demonstration of reaching tissue of interest where it reduces its substrate significantly.

- Providing Evidence of Substrate Reduction

"If substrate levels have high intrasubject variability, efforts to reduce variability may improve the likelihood of a positive outcome. For example, multiple specimens may be obtained from the subject at each time point from the same source and assayed separately and averaged."

This is precisely the way PRX-102 data has been collected to date, due to intrasubject variability on eGFR slope decline.

- Later it also requests data on immunogenicity of the product in patients, which PRX-102 has plenty of and covering over 2 years of usage.

- The guidance makes note of the difficulty of recruiting patients from a rare disease type. One would think that given that understanding, having over 100 patients data to date and covering over 1-2 years, should prove a significant enough sample size.


Based on this guidance, and also given that again PRX-102 is not only gathering data on the surrogate substrate biomarker for efficacy GB3 (which Fabryzyme and Galafold used), but is also using the true most valuable end-point of actual kidney function, eGFR, as well as the benefit of the treatment regimen itself should put 102 in good stead for Accelerated Approval.