Well, here's a nasty surprise for you: your new drug gets a 14 to 1 "Yes" vote from an FDA advisory committee, but the agency turns you down, anyway. That's what's just happened to Savient (OTC:SVNT) and their new biologic product for gout, Krystexxa (pegloticase).
The FDA isn't required to say why they do such things, at least not to anyone else other than the company that submitted the drug. And they're aren't talking this time, either, but it looks like there's a manufacturing issue involved. The process for making Krystexxa seems to have changed a bit since the clinical trial batches, and the agency apparently wants to make sure that this hasn't altered anything. If all goes well, then, you'd expect the company to get things straightened out sometime next year, but for Savient, that's an awful long time to wait.
People who follow the company (and the gout market) have been arguing for the last few years about its prospects. Krystexxa is a pegylated form of an enzyme called uricase (urate oxidase) that clears out uric acid (crystals of which are the proximate source of trouble in gout). Interestingly, this is one of those enzymes that's found all over the various phyla, and in mammals up to primates - but it stops there. We have the gene for the enzyme, but it appears to have been mutated to an inactive form at some point (rather like our gene for the last step in endogenous Vitamin C synthesis - I always wonder what the Intelligent Design people have to say about such things, although I'm pretty sure that it's some variant of "Because it was designed that way for some good reason that's not immediately clear to us right now").
Bringing in this enzyme, then, isn't a case of replacing something that we already have. This is adding a function that we lost back in the early primate days, so we're talking "foreign protein" here. The pegylation is partly there to help with that, and partly just to give the protein a chance to survive the usual metabolic processes. For those who don't know the term, "Peg" is short for "polyethylene glycol", so a pegylated protein has long polymer chains of this hanging off it at various points. The total effect is rather like spraying the thing down with a coat of clear varnish - it changes the solubility, slows down metabolism and clearance, and changes the immune response to the protein. Pegylation is useful indeed, but something of a black art, since it's difficult to predict just what'll happen each time you try it.
Well, I wish Savient luck in getting things straightened out. And I wish their shareholders luck today. The company's stock has not been a place for the easily alarmed over the last year or two, and I'll bet that a lot of people thought that the fear had been cleared by that 14-1 advisory committee meeting. But that's the thing about this whole industry: you can never quite breathe easy..