I wrote some time ago (Ay! Four years ago - have I been doing this for that long?) about the Roche/Trimeris HIV drug Fuzeon (T-20, enfuvirtide), and its costly manufacturing process. Roche built a factory in Colorado just to make the drug, which is a 26-amino acid peptide. And instead of doing it recombinantly, they're producing it the good old chemical way, by peptide coupling. (Here's a not incredibly competent collection of whiz-bang photos of the place, which at least have no purple spotlights in them)
Back in 2002, I had some thought that Roche had perhaps lost its corporate mind. But as this article from Chemical and Engineering News points out (subscriber-only, I think), they've actually done everyone a favor, whether by losing their minds or not. Their decision to go fully synthetic, and the massive investment that followed, has lowered the cost of all sorts of peptide synthesis reagents, starting materials, and equipment, to the point that it's now become enough of an industry to attract a lot more production interest. (And one of the big players in the contract business is. . .Roche's Colorado facility!)
As the article points out, recombinant technology (producing the peptide in engineered cells) is a wonderful thing, but only when it's working perfectly. And getting it to that point can be a long, expensive task. There are a lot of potential cell lines to choose from, each with its own advantages and disadvantages, and uncountable ways to engineer them and culture them. Even then, the purification of the target protein can be a whole new nightmare - as one chemist interviewed by C&EN says, at least synthesis doesn't give you back ten times as many different things as you put into it.
Peptides still aren't anyone's first choice for development when there's a small-molecule alternative. But for the targets that no small molecule is going to hit, they're worth looking at. Recent years have seen improvements in metabolic stability and duration of action, as people come up with all sorts of nifty delivery systems and conjugate polymers. You could do a lot worse.
But perhaps Roche could have done better. There were all sorts of glowing forecasts about Fuzeon when it was first approved, and all sorts of grumbling from people who took the optimistic numbers and calculated that Roche would be making its money back in two or three years at the prices they'd set. Well, that hasn't happened yet, since the drug isn't selling nearly as well as had been hoped.
Another two or three years should do it, if nothing better comes along to cut into Fuzeon sales. And stipulating that (which is no sure bet) Roche might be selling it for a long time to come, since the barrier to generic manufacture is going to be rather high. So, even after that wild factory in Colorado, they're still probably going to go into the black on Fuzeon, but it does make you wonder how the return compares to some of the other drugs in Roche's portfolio.
But that's their problem. In the meantime, it looks like they've helped everyone else in the business by making industrial peptide synthesis more affordable. Adam Smith's invisible hand strikes again. . .
1. secret milkshake on July 20, 2006 1:01 AM writes...
Ferringa company in Europe has been making therapeutic peptides (like analogs of vasopressin) by solid-phase synthesis for decades now.
I have admiration for any process group that is doing a deprotection/support cleavage of a peptide in kilo amounts using vats of anh. HF and then purifying it on giant columns...
Permalink to Comment2. Morten on July 20, 2006 2:17 AM writes...
Chemical synthesis of peptides is awesome. Not being limited to 20 amino acids helps a lot in the design stages. And another advantage is that it's easier to make the peptides protease resistant when you add synthetic amino acids - and an amino acid is still relatively small and simple to make in large amounts through traditional organic chemistry.
Permalink to Comment3. PharmaChemist on July 20, 2006 7:25 AM writes...
Economics aside, the industrial synthesis of Fuzeon is one of the more impressive sytheses of the last decade. For those of you who are involved with synthetic chemistry, by all means try to attend a Brian Bray (Fuzeon lead chemist) lecture describing this work. It is fantastic stuff.
Permalink to Comment4. Don Butler on July 20, 2006 8:04 AM writes...
Parke Davis made Vasopressin and Oxytocin by normal peptide synthesis for decades in Holland Michigan.
Permalink to Comment5. Derek Lowe on July 20, 2006 8:47 AM writes...
True, but those are both nine-amino-acid peptides. Going up to 26 by synthesis alone took some nerve. . .
Permalink to Comment6. agent orange on July 20, 2006 2:18 PM writes...
Roche didn't build the plant there, it was already there, as Syntex, and had been producing peptides for years.
Permalink to Comment7. heziris on July 20, 2006 4:59 PM writes...
as exciting as fusion inhibitors are, i guess the fact remains that it still causes some pretty grim side-effects, and is too expensive to be deployed in third world countries where it is most needed. although there is some time to come before a 'better' drug or even vaccines are available, topical remedies are going to be the next big thing for preventative purposes (although this is definitely going off on a tangent from profitability issues!).
i find your blog insightful derek, and feeling at dis-ease at our level of consciousness in being aware of disease (as opposed to health) and finding a 'cure'.
all the best.
Permalink to Comment8. Al Bundy on July 20, 2006 8:52 PM writes...
First time here and I noticed you worked for pharma on schitzo drugs. I have found that opiates are by far the best drugs for schitzo. Yes opiates. And yes they are very addictive, but even that price is a very fair one to pay because they work so well compared to the poison that pharma markets for this disease. It's sad that smart people get talked into working on this crap. Good blog though.
Permalink to Comment9. Martin on July 21, 2006 6:50 AM writes...
As I recall, Amylin is making Byetta by peptide synthesis.... and they found it to be a pretty cheap process in 2004.
Permalink to Comment10. Maureen Rouhi on July 24, 2006 3:06 PM writes...
Non-ACS members can view the original C&EN story at http://pubs.acs.org/cen/business/84/8429bus1.html
This link is free.
Permalink to Comment11. Naresh Gupta on July 16, 2010 7:16 AM writes...
Fuzeon is not 26 Amino Acid Peptide.. its 36 Amino Acid
Please get the basic facts rights before criticizing....
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