Protalix (AMEX: PLX) is a biopharmaceutical company that is revolutionizing the development and manufacturing of recombinant therapeutic proteins through its ProCellEx™ plant cell-based protein expression system. The company is focused on the development and commercialization of a proprietary pipeline (Figure 2) of novel and biosimilar proteins that target large, established pharmaceutical markets and that rely upon known biological mechanisms of action. Protalix’s initial commercial focus is on complex therapeutic proteins for the treatment of genetic disorders, such as Gaucher disease and Fabry disease. The Company is also advancing other recombinant biopharmaceutical drug development programs, including a TNF inhibitor for inflammatory diseases (aka, Humira, Remicade).
Protalix’s lead product is Uplyso (taliglucerase alfa) for the treatment of Gaucher’s disease. The treatment has orphan drug status in both the EU and US. The product is partnered with Pfizer. Gaucher’s disease is a genetic disease in which a fatty (lipid) substance accumulates in cells and certain organs. The patients (males and females) have a hereditary deficiency of the enzyme glucocerebrosidase (also known as acid β-glucosidase), which causes lipid to accumulate in cells, especially those of the immune system. About 1 in 100 people in the United States are carriers of the most common type of Gaucher disease. The carrier rate among Ashkenazi Jews is 8.9% while the birth incidence is 1 in 450 (remember this!!).
In clinical trials, data from Uplyso were as efficacious as Genzyme’s Cerezyme and Shire’s Vpriv (Figure 1 below). (For Figure 1 – special thanks to Gekkowire for putting together information, and it speaks volumes about his site here). Even more compelling, during Genzyme’s manufacturing issues in 2009, patients were switched over to Uplyso under a Life Savings Use Program from the Department of Health. As of November 2010, PLX submitted a Marketing Authorization Application (MAA) in the EU for Uplyso and the company is awaiting a ruling. In February 2011, PLX was was issued a Complete Response Letter (CRL) from the FDA in regards to Uplyso. The FDA’s CRL caught many off guard; there was no warning in the PDUFA or other documents made public.
The FDA found the manufacturing facilities acceptable according to the 8K filed by PLX. Therefore, the surprise rejection could be due to either a validation plan or the FDA just isn’t ready yet for the technology and wants more time to review it. I think the latter is more likely as the FDA asked for the full switchover data (something that was never asked for in the SPA (Special Protocol Assessment)). The FDA may be stifling innovation by not actively working with companies even after their NDA/BLA has been filed. I still believe that PLX will get approval in the US, and the EU approval should come sometime in Q3 or Q4.