With its new website, Protalix has now provided links to a key publication abstract that discloses the altered glycosylation on Uplyso as compared to the approved glucocerebrosidase products. These are different molecules, and glycosylation is known to affect immunogenicity.
You can't download the article, of course, but they have now disclosed this piece of information. Interesting that the website is revamped and this material is posted right before they are supposed to hear back on PDUFA...
The data for Uplyso is as good as it gets for a biologic agent treating this rare disease. Regarding the side effects of this drug, there is no escaping the hypersensitivity reaction seen with a biologic agent.
To response to Jrus comment regarding a possible CRL requiring futher studies specifically looking at immunogenicity, I would have to say that anything is possible, but highly unlikely. First of which, this is a life-saving drug and not a life-style drug, hence the approval criteria are different. But most inportant of all, the FDA can only use historical data to compare its safety to that of others in its class. It's not realistic to conduct a trial looking at immunogenicity bc it will require protalix to compare its drug to Genzyme. Furthermore, the trial would require too many patients to recruit for a rare disease like Gaucher in order to detect a possible statistical difference in clinical immunogenicity.
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.