This year was a big year for antibiotics. The FDA approved
four new antibiotics this year including dalbavancin and oritavancin, two
long-acting glycopeptide antibiotics that can provide for one or two dose
therapy for serious skin infections. They approved tedizolid, a new and
improved oxazolidinone active against some linezolid-resistant strains of
staphylococci and available in both oral and intravenous formulations. Cubist's Ceftolozane-tazobactam was the only antibiotic targeting resistant Gram
negative infections to be approved this year. As covered in this blog several
weeks ago, the FDA advisory committee recommended that Actavis' ceftazidime-avibactam be
approved for urinary tract and intra-abdominal infections when there are few or
no alternative therapies available. This
latter was based primarily on phase 2 clinical data – a historical precedent
for the FDA in its antibiotic approval history. Four new antibiotics in a
single year breaks a record for the FDA going back to the 1980s or perhaps the
early 1990s and it certainly provides a respite in the drought of approvals
over the last 20 years.
In addition, looking ahead to 2015, we can expect at least
one important approval. Eravacycline
from Tetraphase has already completed a trial in intra-abdominal infection and
will soon complete its trial in urinary tract infection. They should file in the first half of 2015
and, with any luck will receive approval later in the year. This is an
important product because it is active against resistant Gram-negative
pathogens AND IT WILL BE ORALLY BIOAVAILABLE.
This offers the potential to prevent hospital admission for large
numbers of patients who today are admitted to hospital to receive intravenous
therapy simply because none of the oral drugs will work because of bacterial
resistance.
Unfortunately, 2015 is not going to be a banner year for
antibiotics. 2014 represents what
happens when the pipeline has lain dormant for five or six years and suddenly
wakes up to the light of day (thanks mainly to FDA dithering). In 2015 we will be back to the reality of a
pipeline that still desperately needs new entrants.
Cempra’s solithromycin, a new ketolide antibiotic for the
treatment of pneumonia and highly resistant gonorrhea has completed its phase 3
trials for the oral formulation of the drug in community acquired
pneumonia. Cempra has not provided a
timeline for its NDA submission as yet – but it seems unlikely that it will be
in 2015.
For resistant Gram-negative pathogens, looking farther into
the future, we have Merck’s Relebactam (imipenem-cilastatin-MK7655) languishing
in phase 2. MK7655 is a beta-lactamase
inhibitor closely resembling avibactam. There is Rempex-Medicine Company and
Carbavance in an interesting phase 3 trial targeting highly resistant
pathogens. Carbavance is a combination of a novel beta-lactamase inhibitor with
meropenem. Finally, there is the aminoglycoside, plazomicin, from Achaogen that
is active against many resistant Gram-negatives as well.
One drug to keep an eye on is the combination of
aztreonam-avibactam by Astra-Zeneca, which would be one of the very few antibiotics active
against NDM-1 like superbugs. While it
is still only in phase I, I think that it could be ready for submission in the
next couple of years. This would be a
real breakthrough product for those most highly resistant organisms that only
eravacycline can now approach.
Last
year I predicted that at least one additional large pharmaceutical company would
re-enter the antibiotic R&D space.
That has not happened. Not only
that – but I took a more optimistic stand on Astra-Zeneca suggesting that maybe
the CEO would see the error of his ways.
That has also apparently not occurred and AZ
seems to be about to divest itself in one way or another of its antibiotic
R&D. On the other hand, Merck
clearly expanded their effort with their purchase of Cubist. I still
believe that other large pharma companies will take the plunge – hopefully in
2015. The medical need is clearly there.
The economic climate for new antibiotics is going to improve. And the
regulatory pathways have already vastly improved especially in the US (because
they had much farther to go) but also in Europe.
Speaking about regulatory pathways – we have yet to see
companies truly take advantage of the rapid paths now available in Europe. I’m
not sure I see that happening until after 2015.
I do believe, though, that at least one company will establish a pathway
forward for a pathogen specific indication either in Europe or in the US in
2015. (I have been predicting this for
two years now – but I still think its coming).
To keep you up to date on the activity of the blog – we broke
the 200,000-view mark this year. In
order, the most popular blogs have been; (1) John Quinn – In Memoriam (5415 views) (Don’t
forget the John
Quinn Memorial Fund); (2) Antibiotic
Markets and SPLU (the old LAPD) (5244 views); (3) Rebooting
Hospital Acquired Pneumonia from 2012 (3809 views). Other popular blogs
included Astra-Zeneca
is Cutting and Running, and, for some reason, Antibiotics
in 2012 – an old end of year summary.
With that, I can only wish all of you the best in 2015. For myself, for the first time in a long
time, I am seeing bright lights at the end of an ever-shrinking tunnel.
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