* Roche's return bucks broader retreat by Big Pharma
* Has struck three small deals since last November
* Better diagnostic tests key to targeted treatments
* Regulatory, legislative changes encourage new research
By Caroline Copley
ZURICH, June 2 Roche is betting the
same tools that made it the world's largest producer of cancer
drugs will help it tackle the growing public health crisis of
antibiotic resistance as regulators and politicians encourage
The Swiss drugmaker used its expertise in in vitro
diagnostic tests to develop highly-targeted cancer medicines.
Now it believes it can use those same skills to find out quickly
which bugs cause which infections, and help doctors kill them.
Experts are currently warning that superbugs resistant to
even the most powerful drugs threaten to undermine modern
medicine - requiring a response on the same scale as efforts to
combat climate change.
Infections that are resistant to antibiotics affect more
than 2 million people in the United States every year and kill
around 23,000 people as a result, according to the Centers for
Disease Control and Prevention.
"Bacteria are probably smarter than we are and they're
always evolving," said Janet Hammond, global head of infectious
diseases at Roche's pharma research and early development unit.
Roche pioneered some of the more modern penicillins, but
wound down its research at the end of the 1990s.
However it has been quietly rebuilding its expertise over
the past two years. It struck a deal for the license of an
experimental antibiotic from Switzerland's Polyphor last
November and formed a partnership with Britain's Discuva and
U.S. biotech Spero Therapeutics earlier this year.
"We're very optimistic that we have a good chance of success
or we wouldn't be going back into the space, but it's certainly
not a slam dunk," Hammond said.
BIG PHARMA RETREAT
Roche's return to the field runs counter to a gradual drift
to the exit by Big Pharma over the past decade: Only a handful
of pharmaceutical firms with large antibiotic R&D programmes
remain, compared to nearly 20 in 1990, according to the
Infectious Diseases Society of America (IDSA).
Faced with dwindling returns on antibiotics R&D, drugmakers
Bristol-Myers Squibb Co, Eli Lilly and Co and
Pfizer Inc switched their focus to cancer and chronic
diseases that command higher prices and are taken for longer.
AstraZeneca PLC, which has the most developed
pipeline of the remaining players, recently also said it would
put less money into the business.
As a result very few new antibiotics have come to market
over the past few decades, leaving doctors with very few weapons
to fight serious and life-threatening infections.
Regulators are now looking to speed up the approval of any
new antibiotics, and U.S. politicians are working on new
legislation like the Developing an Innovative Strategy for
Antimicrobial Resistance (DISARM) Act to remove obstacles - such
as the current payment systems - that are putting companies off
from developing new drugs.
Those measures, as well as legislation like the 2012
Generating Antibiotic Incentives Now (GAIN) Act - which offers
drugmakers an extra five years of market exclusivity - have
played a part in tempting back not only Roche but also a slew of
smaller firms like Cubist Pharmaceuticals, The
Medicines Company and Basilea.
Most antibiotics used today are "broad spectrum" products,
which can kill a wide range of bugs but are also responsible for
breeding resistance because they damage gut flora creating an
environment for infections to flourish.
But Roche believes developing tests that can accurately
identify within a matter of hours which microbe caused an
infection will help it push ahead.
Unless such tests to speed up the diagnosis of infections
become available, physicians will be pushed to keep prescribing
"broad" products, said David Livermore, a professor in medical
microbiology at the University of East Anglia who has spent more
than 30 years researching antimicrobial resistance.
Roche's most advanced product is the antibiotic from
Polyphor, currently in mid-stage testing, and targets just one
bacteria: multi-drug resistant pseudomonas aeruginosa.
Although Roche is not developing a companion diagnostic - a
test to predict which patients will respond best to therapy -
alongside this antibiotic, it is exploring new ways to identify
infections more quickly and accurately through the collaboration
of its pharma research and early development unit and diagnostic
The Swiss company is also interested in researching
treatments for hospital-based infections that are difficult to
treat, such as those called by "Gram-negative" bacteria, as well
as opportunities to treat prosthetic joint infections and
endocarditis, a rare and potentially fatal type of heart
infection, Hammond said.
REINVIGORATE - CAREFULLY
Roche may for now be the only member of "Big Pharma" to look
again at antibiotic research, but top healthcare officials are
hoping to lure more back.
"We need to explore what it is that would reinvigorate this
system to produce not just one new antibiotic, but a steady
series going on for decades," said Sally Davies, Britain's chief
medical officer who last year warned antibiotic resistance was a
"catastrophic threat" to health.
However - should these attempts prove successful enough to
spur a new range of medicines, the commercial rewards ought to
be delinked from the number of prescriptions, warned Alex White,
head of Roche's team that looks for licensing deals in the field
of infectious diseases.
Otherwise, indiscriminate usage of the new antiobiotics
could only breed new superbugs.
"One of the paradoxes of antibiotic development is that the
more successful you are in developing a really good antibiotic
that you then license and launch in the market place, the less
you really want it to be used unless it's absolutely necessary."
(Additional reporting by Kate Kelland; Editing by Sophie