A few observations and a question regarding sepsis for the board:
I recently read an article which suggested that Genzyme was having some trouble scaling up their product for Pompe's disease
from a smaller batch process to a larger one. I don't know whether this story is true for Genzyme and Myozyme, but I do know that product consistency when scaling up cell culture volume sometimes is a real challenge. Which leads me to note that this is another advantage of this technology over cell culture. Also, from a potential partners point of view, I think Ayryn would be most attractive considering the size of the potential markets coupled with the fact that a partner will not have to build a factory nor will they have to answer the question--will it scale?
Regarding sepsis. there are lots of clinical studies at clinicaltrials.gov but I only noticed two, besides Atryn, which look like they might be a potential treatment for DIC and sepsis. Both drug candidates are in phase 3, both by Japanese companies, Takeda, and Eisai. and they both 'down regulate' something called 'toll-like receptor 4'. Toll-like receptors activate the immune system and TLR-4 is is engaged by 'gram-negative bacteria'. While Takeda and Eisai were willing to go to 2000+ patient phase 3 trials it looks to me as though the TLR4 antagonists will only be potentially useful in about 1/2 the sepsis cases as only about 1/2 are caused by gram-negative bugs. The only half are caused by gram-positive bacteria and thus it would seem that dialing down TLR-4 would not be helpful in the gram-positive cases. My knowledge of this subject is superficial so can anyone on the board clarify this?
My second question is that it also would seem that the use of a TLR-4 antagonist and antothrombim may be mutually beneficial as on one end you are down regulating an overheated immune response and on the other end you are supplementing a depleted antithrombin condition.
Finally, since sepsis is due to an rapidly progressing infection, I wonder if 'down-regulating' the immune system will cause other problems. Antibiotics may deal with the infection if the patient survives but I guess that's one of the reasons for a phase-3.
