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PLX's product is produced in plant cells, and the protein has plant carbohydrates (sugars) decorating it. Genzyme's and Shire's products are produced in mammalian cells and have different sugars decorating them. These sugars trigger immune responses and plant sugars are known to be more immunogenic than non-plant sugars. Furthermore, PLX's own publication states that the crystal structure is different for their product.
In short, these cannot be considered to be the same molecule. While every should have done their own diligence, my own belief going into the PDUFA is that the FDA will flag them with a CRL for having inadequate clinical trials that do not sufficiently demonstrate that their product does not have worse immunogenicity than approved products. We shall soon see. Good luck.
6% of patients in PLX's phase III study developed antibodies to Uplyso and 6 percent of experienced hypersensitivity (all of which were resolved). In contrast, historical data put Cerezyme's antibody rate at about 15 percent and hypersensitivity rate at 7 percent. The theoretical fear of immune reactions to this particular plant derived enzyme does not match the actual real life data. Yes, everyone should do their own DD.
Awesome post! ROTFLMFAO!!!!! Thanks, Scoob!
There is this as well - from the link jrus posted:
"...These studies demonstrate the safety and lack of immunogenicity of prGCD. Following these encouraging results, a pivotal phase III clinical trial for prGCD was FDA approved and is currently ongoing."
"It remains to be determined in larger scale clinical studies, as required in any new protein drug development process, whether plant-derived biopharmaceutical glycoproteins are associated with any excessive immunogenicity effects or excessive neutralizing antibody formation, beyond the standard rate seen for recombinant therapeutic proteins, which may limit their use. However, the current regulatory viewpoint, based on data accumulated in a number of clinical trials involving different plant-expressed proteins, is quite promising in this regard , . The clinical and preclinical data presented herein and reported previously , demonstrated that there were no obvious treatment-related adverse reactions or clinical findings, indicating the potential safety of plant cell-expressed GCD."
And this - from the 8K on 1/27/11 - slide #26.
One more - https://crosscurrentllc.com/uploads/GENZ_10-15-09_Protalix_Phase_3_Data_Look_Good__Putting_Heat_on_GENZ.pdf
Hey jrus - go load the boat with ANX and PSDV. LOOOOOOOL!
Nomoney - never rely upon a message board for DD, particularly coming from this jrus character. One check of his posts and you will see he is a basher of PLX and his other "picks" have been stellar - ANX (LMAO!!), PSDV (ROTFLMAO!!)
He also bashed CLDA indicating no buyout would occur. Granted today's buyout was a blow to the longs, but it happened nevertheless.
Even his "DD" is contradictory. Read his reply carefully and you will see what I mean.
I will try to post more on this later, but keep in mind that Uplyso's Phase 3 trials were done under an SPA with the FDA. Look it up, but that basically means PLX and the FDA agreed upon the trial's design and endpoints.
Roughly 15% of patients receiving current enzymes develop antibodies even though these are mammalian derived. No one (who knows anything about this product) is considering it the exact same molecule. Here is the abstract form one of the articles:
Gaucher's disease, a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy using recombinant GCD (Cerezyme) expressed in Chinese hamster ovary (CHO) cells. As complex glycans in mammalian cells do not terminate in mannose residues, which are essential for the biological uptake of GCD via macrophage mannose receptors in human patients with Gaucher's disease, an in vitro glycan modification is required in order to expose the mannose residues on the glycans of Cerezyme. In this report, the production of a recombinant human GCD in a carrot cell suspension culture is described. The recombinant plant-derived GCD (prGCD) is targeted to the storage vacuoles, using a plant-specific C-terminal sorting signal. Notably, the recombinant human GCD expressed in the carrot cells naturally contains terminal mannose residues on its complex glycans, apparently as a result of the activity of a special vacuolar enzyme that modifies complex glycans. Hence, the plant-produced recombinant human GCD does not require exposure of mannose residues in vitro, which is a requirement for the production of Cerezyme. prGCD also displays a level of biological activity similar to that of Cerezyme produced in CHO cells, as well as a highly homologous high-resolution three-dimensional structure, determined by X-ray crystallography. A single-dose toxicity study with prGCD in mice demonstrated the absence of treatment-related adverse reactions or clinical findings, indicating the potential safety of prGCD. prGCD is currently undergoing clinical studies, and may offer a new and alternative therapeutic option for Gaucher's disease.
And from the other article highlighting phase I human studies:
"Administration of prGCD did not result in the formation of anti prGCD antibodies in any of the patients. Overall, prGCD presents a high safety profile."