SPECIAL REPORT – When the drugs don’t work

There are two main reasons for this. First and foremost
antibiotics, when they work, tend to cure people. Patients take
small quantities for several days, a few weeks at most. That’s
not a very attractive revenue flow. By contrast, a patient on a
cholesterol-lowering heart medicine will keep using the pills,
and contributing to drug industry profits, for the rest of his
or her life. Second, even if a new antibiotic is approved for
sale, its use is likely to be reserved for serious infections —
once again, minimising the sales opportunity.

To cap it all, most existing antibiotics have been around
for decades and are widely available as cheap generics, setting
a very low bar for prices.

“If you are in the business of antibacterials, I think you
just have to accept that is the way it is,” says Mackay. “Will
it be as profitable as a really great cardiovascular drug?
Probably not.”

So it should be no surprise that while the global market for
all prescription drugs grew by more than 40 percent over the
last five years, the value of sales of antibiotics shrank to
$14.4 billion in 2010 from $16.1 billion in 2005. That figure is
projected to fall to $12.0 billion in 2015 as some former
blockbusters lose patent protection, according to consensus
analyst forecasts compiled by Thomson Reuters Pharma.

Faced with such economic hurdles — not to mention the
daunting scientific difficulties of outwitting fast-mutating
superbugs — a long list of big drug companies have decided to
end their antibiotic research, including Roche Holding AG,
Bristol-Myers Squibb Co and Eli Lilly & Co.

AstraZeneca and GlaxoSmithKline — and to a lesser extent
Novartis AG, Merck & Co Inc and Pfizer Inc — remain in the
antibiotic space. But scientists like Livermore fear work in
drug company labs is being disrupted by the upheaval now
sweeping the industry, following a wave of mergers and
acquisitions. That’s diverting attention from the job at hand:
battling the microscopic pathogens that are threatening the
practice of modern medicine.

BARRIERS TO ENTRY

But the buck doesn’t stop with Big Pharma. Despite urgings
from officials at the FDA and its European equivalent for drug
companies to do more, many in the industry believe that
regulators are actually a large part of the problem.

David Shlaes, a 30-year industry veteran who now works as a
consultant, has particularly harsh words for the FDA, accusing
it of a “lurch into Neverland as far as antibiotics are
concerned” in an open letter to U.S. Secretary of Health and
Human Services Kathleen Sebelius in February.

The problem, as critics like Shlaes see it, is the
increasingly onerous nature of clinical trials demanded by
officialdom before an antibiotic can be approved for sale.
Regulators have grown much more cautious about clearing new
drugs in recent years: the situation is especially sensitive in
the case of antibiotics, following a scandal over Sanofi-Aventis
SA’s Ketek, which was approved in 2004 but subsequently linked
to a risk of liver damage.

The result is a belt-and-braces approach to testing new
antibiotics that means experimental antibacterial drugs need
more and much larger late-stage clinical studies, throwing up
what senior Pfizer research executive Rod MacKenzie says is now
the principal obstacle to antibiotic development for the handful
of big players still left in the game.

“That’s of course where the large bulk of our costs are —
in the late stage of development — and so that really makes
life very difficult,” he says.

The pushback isn’t just coming from the industry: Livermore
is also convinced society needs to adjust its risk dial and make
it easier for new antibiotics to win approval if it wants to
secure a flow of future drugs. “As a result of seeking the
perfect we risk squeezing out the good,” he says. “It would
introduce more risks — but the biggest risk, looking forward,
is that we are simply not going to get enough new antibiotics.”

“PUSH-ME, PULL-YOU”

Experts from science and industry meet often in conferences
to ponder the problem. One such get-together in a swanky hotel
in central London this month had the catchy title “Superbugs and
Superdrugs”. Unfortunately, the bacteria right now are proving a
lot more “super” than the medicines, the delegates agreed, and
many pharmaceutical industry investors are losing their appetite
for the fight.

Fixing the system, experts argue, will require a mixture of
“push” and “pull” incentives – “push” measures to lower the cost
of developing new antibiotics, and “pull” factors to increase
the commercial rewards for successful products.

Adjusting the “pull” side of the equation may be the most
controversial, since it effectively means offering a form of
subsidy to drug companies. But the Infectious Diseases Society
of America, which has called for a global commitment to develop
10 new antibiotics by 2020, believes stronger financial
incentives are vital. Options include tax breaks, patent
extensions or government commitments to buy future drugs. Some
academics have also proposed more complex systems that would
offer rewards based on how long a new product is on the market
before resistance develops. The risk for taxpayers, of course,
is that companies end up “gaming” any new reward system — to
the advantage of their shareholders but not necessarily society.

Ultimately, we may simply have to accept that antibiotics
should no longer be cheap. Rather, they would become
premium-priced products along the lines of targeted cancer
therapies, which can cost tens of thousands of dollars a year
for each patient. It would be a radical change, and price out
many in the developing world, but a high price would, at least,
have the advantage of deterring over-use and helping to fund
research, particularly in more narrowly targeted drugs.

Changing the business model could also open the door to new
approaches to treatment. There’s certainly plenty of room for
improvement, since the current diagnosis of bacterial infection
by growing cultures hasn’t changed fundamentally in decades. In
the future, scientists hope rapid point-of-care diagnostic tests
will allow them to identify their adversaries within hours,
making treatment decisions quicker and allowing drug companies
to conduct small, focused clinical trials targeting a narrow
population group.

All promising ideas, but not much is happening yet. The WHO
is working on a six-point plan to target health authorities,
doctors and patients. Its main message: superbugs are not just a
problem for the old and the sick — this affects everyone.

Runner Steve Owen is the first to admit he finds the
realities of what we face difficult to grasp. He knows that he
lost his father because levels of hygiene in the hospital were
too low. But why is the pace of drug development so slow? Why
can’t we do more to fix the problems that killed his dad?

“I’ve always thought that science would advance and keep up
pace with the bugs, not that the bugs would get ahead of the
expertise of the scientists,” he says. “It’s frightening.”
(Edited by Sara Ledwith and Simon Robinson)

SPECIAL REPORT – When the drugs don’t work