cerezyme.PNGUnremarkably, I was totally stuck at O’Hare last night until midnight waiting for a flight that was supposed to take off around 6:00. This being the second time in less than 30 days that O’Hare made me want to die. I mean… Fuck O’Hare. Anyway, given my late arrival and sleeping in later than normal, I’m sitting around with little to nothing to do waiting for mummy Finchsigmate to arrive home with delicious scrambled caviar and figured I’d do a little post on a drug most people probably haven’t heard of.

Cerezyme is freeze dried imiglucerase, a recombinant (and modified) form of the enzyme Glucocerebrosidase and it costs about $200,000 a year for life. It’s one of three treatments for Gaucher’s disease which doesn’t involve scooping organs out with a spoon before they explode or topping the ‘ol femurs off with some new bone marrow. (The others are Miglustat, a small drug and Ceredase, an enzyme derived from leftover placenta… fuckin’ gross.) In general, you don’t have to worry if you aren’t an Ashkinazi Jew or a Sweed from Norrbotten, as they are the ones that seem to be afflicted.

The drug is made inside CHO cells, which are just Chinese hamster ovary cells that have been transfected to produce imiglucerase. Imiglucerase is not the real deal; since they do not produce the actual Glucocerebrosidase, 15% of patients develop antibodies to the drug and of those about half have an allergic reaction. My understanding is that the modifications, specifically the Mannose sugars on the terminus of the existing polysaccharide chain, lead to a selective uptake of the enzyme by macrophages that are resent in liver, spleen and skeleton. Without this modification the drug does not work effectively.

The drug works just like the natural protein by catalyzing the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide as part of the normal degradation pathway for membrane lipids.

If you want to make your own, here is the sequence:

ARPCIPKSFGYSSVVCVCNATYCDSFDPPTFPALGTFSRYESTRSGRRMELSMGPIQANH
TGTGLLLTLQPEQKFQKVKGFGGAMTDAAALNILALSPPAQNLLLKSYFSEEGIGYNIIR
VPMASCDFSIRTYTYADTPDDFQLHNFSLPEEDTKLKIPLIHRALQLAQRPVSLLASPWT
SPTWLKTNGAVNGKGSLKGQPGDIYHQTWARYFVKFLDAYAEHKLQFWAVTAENEPSAGL
LSGYPFQCLGFTPEHQRDFIARDLGPTLANSTHHNVRLLMLDDQRLLLPHWAKVVLTDPE
AAKYVHGIAVHWYLDFLAPAKATLGETHRLFPNTMLFASEACVGSKFWEQSVRLGSWDRG
MQYSHSIITNLLYHVVGWTDWNLALNPEGGPNWVRNFVDSPIIVDITKDTFYKQPMFYHL
GHFSKFIPEGSQRVGLVASQKNDLDAVALMHPDGSAVVVVLNRSSKDVPLTIKDPAVGFL
ETISPGYSIHTYLWRRQ + manoses

Why is it $200,000 a year? Maybe more, depending on your dosage needs? Certainly not all recombinant drugs are this expensive. Insulin has been grown in bugs for almost a decade and it’s dirt cheap in comparison.

The answer is that, quite simply, there are probably only 10,000 people in the world with this disease and 5,000 of them are already on it. To recoup that investment they needed to put the price point higher. But it’s an orphan drug! They already got a shitton of money back from the gubment for just making it, why do they need to sell it for such a shitton of money it actually has sales in excess of a billion dollars a year?

Well, that’s one of them sticky ethical questions that the ChemBlog is running out of time to answer… Caviar is almost ready.