Yesterday, Roche, Meiji and Fedora pharmaceuticals announced
a deal that could be worth up to $750 million to develop OPO595, Fedora’s phase
1 DABCO B-lactamase inhibitor. Roche will develop the drug throughout the world
with the exception of Japan where Meiji will obtain commercialization
rights. I was unable to find the details
of the deal – but this is the broad outline according to a Fedora
press release.
There are a number of fascinating aspects to this. The President and CEO of Fedora is Christopher G. Micetich, the son of Ron
Micetich. Ron was the discoverer of
tazobactam, one of the early inhibitors of B-lactamase and marketed by Wyeth as
piperacillin-tazobactam – a billion dollar plus product. I was involved in the
early days of tazobactam showing that piperacillin would be a good partner for
the inhibitor. Later, I helped develop
the drug in the clinic and even later was involved with the marketing strategy
for piperacillin-tzobactam for Wyeth. The world is so small . . .
Once again, this deal clearly shows that Roche is serious
about getting into antibiotics. This
will be their second major clinical stage deal after their deal
with Polyphor late in 2013. It also leads me once again to question exactly
what they are doing.
As far as I can tell from published data from ICAAC in 2013,
OPO595 is a DABCO type non-beta-lactam beta-lactamase inhibitor – that is – it
is similar to both avibactam and Merck’s MK-7655. Avibactam (partnered with ceftazidime) has completed one
phase 3 trial and will complete another soon.
The FDA’s advisory committee has already voted
to approve avibactam (combined with ceftazidime) mainly based on its phase
2 data. Merck’s MK-7655 is partnered
with imipenem and is still in phase 2 trials as far as I can tell. But both of
these DABCO inhibitors are years ahead of OPO595 which is only in phase 1. Why
would Roche leap into a third DABCO inhibitor.
Perhaps they are thinking about its “enhanced” anti-bacterial activity beyond
its ability to inhibit beta-lactamases. But my experience (and I have a lot of it) with this class is that some
antibacterial activity is typical.
Avibactam can have activity against E. coli at as low as 4 ug/ml. Novexel had a DABCO compound, NXL-105, with
activity against Pseudomonas aeruginosa that was thought to be partly related
to its ability to bind PBPs of Pseudomonas.
In fact, the entire DABCO series started at Roussel-Uclaf targeting antibacterial activity through PBP
binding and was only later discovered to have potent B-lactamase inhibition activity.
So I’m not convinced that OPO595 will have much of an advantage over the other
DABCOs based on data published so far.
One potential strategy for Roche/Meiji would be to try and
quickly develop a combination with a monobactam similar to the
aztreonam-avibactam combo that is in phase 1 trails at AstraZeneca. This combo
has the advantage of being active not only against Gram negatives bearing
extended spectrum beta-lactmases, but also against those harboring
metallo-beta-lactamase like the NDM-1 superbugs. Many of us have been screaming
at AZ to develop their version of this quickly for years – but so far – no dice.
Here Roche/Meiji might try and beat their competition to market with this combination targeting NDM-1 like superbugs - and go on from there. But will this pay off? We await further
developments . . .
No comments:
Post a Comment