An ongoing dialogue on HIV/AIDS, infectious diseases,
January 10th, 2010
Ceftobiprole’s Long Road to Approval Gets Longer
Cephalosporins with activity against MRSA are out there, but we don’t have them yet. Just recently, the leader of the pack, ceftobiprole, hit another roadblock:
The FDA has indicated in its Complete Response Letter to Johnson & Johnson PRD that it has completed the review of the application and has determined that it cannot approve the application in its present form … The Agency determined that data from Studies BAP00154 and BAP00414 cannot be relied upon because inspections and audits of approximately one-third of the clinical trial sites for these studies found the data from a large proportion of these sites to be unreliable or unverifiable, raising concerns regarding the overall data integrity for both studies
The recommendation from the FDA? Do more studies. (Which means more delay, more $$$.)
One of the great frustrations of antibiotic development is that there’s clearly a need for better drugs for MRSA — unlike, say, a new PPI — yet this pipeline has been pretty dry.
In fact, I bet not a day goes by in medical centers that this need is not readily apparent to ID doctors, surgeons, intensivists, pulmonologists, nephrologists (don’t dialysis patients seem to have the hardest time with MRSA?), endocrinologists (except maybe for people with diabetes), transplant specialists. Pretty much everyone knows this bug is common and hard to treat.
If we start with the premise that vancomycin is the gold standard — and a fairly tarnished one at that — what are our alternatives? Linezolid was a big advance (especially because it can be given orally), but it was approved ten years ago, is bacteriostatic, has certain unavoidable toxicity issues, and is costly, especially compared to other oral antibiotics. Daptomycin was a somewhat smaller step forward, and I confess I still haven’t had the occasion to use telavancin. Trimethoprim-sulfa and tetracyclines are active, but likely less so than vancomycin.
And ceftobiprole? The initial application to the FDA was submitted in 2007; it is already approved in several other countries. And while I have no idea whether the efficacy and safety of the drug will be preferable to what we have now — perhaps someone from Canada or Hong Kong or Europe can clue me in — just having more options for MRSA seems like a very good thing.
Ceftaroline/NXL104, anyone?
7 Responses to “Ceftobiprole’s Long Road to Approval Gets Longer”
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
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Paul, I have been looking on line to see which other countries have approved ceftobiprole and have not been able to find the information. Which countries have approved it for use? Thanks
Barbara:
From the Basilia web-site (which now has the drug back from J and J after a recent negative European review):
“Ceftobiprole is marketed in Canada (ZEFTERA(TM)) for the treatment of cSSSI, including non-limb threatening diabetic foot infections without concomitant osteomyelitis and in Switzerland (Zevtera(TM)) for the treatment of cSSTI including diabetic foot infections without concomitant osteomyelitis.”
Just came across this conversation via Google. It looks like Canada has withdrawn approval, citing reservations harbored by the U.S. FDA about reliability of trial data (link: http://www.marketwire.com/press-release/Discontinuation-of-sale-of-ceftobiprole-in-Canada-SWISS-BSLN-1167383.htm ). One step forward, two steps backward.
Interesting…
Good chance ceftaroline will be our first anti-MRSA cephalosporin.
I find your objection strange; the FDA said (reading between the lines) you did crappy clinical science, and we can’t actually tell of this drug works.
Since you (the vendor) are gonna make huge sums on it, you might have a bias toward submitting biased results; hence , you have to show that you are on the up and up.
what on earth is wrong with that ?
this is entirely the fault of the drug company, you do a study like this, millions of dollars, you hire some consultants, many ex FDA, and they say, this is what you have to do to do it right.
the drug company screwed up, why should the fda give thema pass ?
Ezra, this is old news now (esp since ceftaroline was approved), but my point was not so much to object to the FDA action, but to express my frustration at the lack of good treatments for MRSA.
Let’s see if ceftaroline is truly an advance when it (finally) arrives.
Dr. Sax, now that Ceftaroline has been out for a while, do you think it’s truly an advance in treating MRSA?