MAY JUNE 2018 | MOTHER JONES 59there have been so few licensing attempts.
It won’t even comment on how many li-
censing attempts there have been, though
the ClinicalTrials.gov database maintained
by the National Institutes of Health shows
that in the United States over the past two
decades, 15 studies have used phages: Just
two applied phages as a treatment and got
through phase one—which uses a small
group of people to test safety but doesn’t
test eicacy—and those studies did not
proceed. The fda declined to make any of
its scientists available for an interview. A
spokeswoman, Megan McSeveney, said in
a statement that the agency “stands willing
to work with bacteriophage developers to
provide scientific guidance and clarify reg-
ulatory and data requirements necessary
to move these products forward in devel-
opment as quickly as possible.”
The nih, which focuses purely on re-
search and isn’t responsible for drug licen-
sure, was a little more forthcoming. “Given
the problems that we have with antibiotic
resistance in this country and through-
out the world, it certainly behooves us to
explore alternative means of controlling
and fighting and countering bacterial in-
fections,” Dr. Anthony Fauci, director of
the nih’s National Institute of Allergy and
Infectious Diseases, told me. “Certainly
phage therapy is one of those.” In 2016,
Fauci said, the nih wrote about $5 million
in grants to medical research centers to
gather data on antibiotic alternatives, in-
cluding phage therapy’s potential against “a
variety of recalcitrant infections.” (The US
medical establish ment isn’t alone in strug-
gling with phage research; the first major
EU-backed clinical trial, called Phagoburn,
did not proceed beyond phase two.)
Elsewhere in the nih, Randall Kincaid,
a pharmacologist and the senior scientific
oicer in what’s called the concept accelera-
tion program, explained that launching new
categories of treatments isn’t as simple as
working out the right structure for a clinical
trial. The research has to be worth the end
result, he said—which means knowing that
physicians will use the treatments when the
compounds enter the market, and also that
pharmacy managers will buy them.
“You have spectacular life-and-death sto-
ries, and everyone wishes to see this pushed
forward as concerns about antimicrobial
resistance increase, yet you have the real
dilemma of demonstrating that these are
in fact reliable,” he said. And commercially
viable: Since phages are hyperspecific and
can’t be pulled off a pharmacy shelf as an
antibiotic can, physicians may be deterred
from seeking them out, he added—and
that would make the trouble and expense
of clinical trials pointless.
A set of treatments that the fda recently
accepted might show a path forward for
testing and approving phages. Personal-
ized cancer treatments known as car-t (for
“chimeric antigen receptor T-cell therapy”)
involve extracting immune system cells
from a patient’s blood so they can be genet-
ically modified in a lab and then re infused
into the patient. In 2017, the fda gave li-
censes to two car-t treatments, Kymriah
for advanced leukemia and Yescarta for a
type of lymphoma.
Like phages, car-t treatments are tuned
to an individual patient. But here’s a keydifference that made drug developers
think car-t was worth pursuing for two
decades: If it goes into widespread use, it
will make manufacturers tons of money.
The cost of a single dose of Kymriah is pro-
jected to be a breathtaking $475,000. But
antibiotics have never been priced any-
where near as high as cancer drugs, and
it seems unlikely that prices would rise
for the phages that might supplant them.
Those low prices have hist orically been
one reason it has been hard to get drug
companies to develop new antibiotics.
Consider: In contrast to Kymriah, the an-
tibiotic Avycaz, hailed as a major advance
when it was approved in 2015 for hospital-
ized cases of grave drug-resistant pneumo-
nia, costs as little as $3,500 on price lists
and rarely rises above $15,000—and that’s
for 10 doses.
For phages to justify investment, devel-
opers will have to make a case for using
them not just to save the 23,000 people
who die of resistant infections in the
United States each year, but also to treatsome of the 2 million who seek a doctor’s
help or hospital care. There are applica-
tions: Phages could coat artificial joints
and heart valves to prevent pathogenic
bacteria from developing sticky drug-
resistant mats called biofilms. Phage solu-
tions could be infused into the raw sur-
faces of diabetic foot ulcers, which are hard
to treat because they have a thick, fibrous
backing that prevents intravenous drugs
from penetrating; that is partly why di-
abetic patients were among the first vic-
tims of vrsa, a staph resistant to even the
last-resort antibiotic vancomycin. Intra-
lytix has proposed using phages to kill dis-
ease bacteria that are picked up from food
and water and live quiescently in the gut
for unpredictable periods of time—the su-
perbugs ndm and mcr, which originated in
India and China, spread around the world
that way. The process of clearing out badbacteria that aren’t currently causing an
infection is called decolonization, and it’s
diicult to accomplish with antibiotics,
which kill good cells along with bad ones.
Phages could be more targeted.
A handful of companies still believe
in the possibility of phages, enough to
invest in research while the fda works out
its issues. One is AmpliPhi Biosciences,
which conducted one of those phase-
one treatment trials in the nih database.
AmpliPhi sits north of the ucsd medical
center where Patterson was treated, and
its phages were among those that became
part of his treatment after Young at Texas
A&M launched his worldwide plea for
phages that might help.
Paul Grint, AmpliPhi’s ceo, is a physi-
cian who was a successful antibiotic de-
veloper earlier in his career and under-
stands from the inside the Catch-22 of the
federal research bureaucracy. The compa-
ny’s phase-one trial investigated the safety
(but not the effectiveness) of a cocktail of
three phages thatStrathdee posted a desperate
plea on Twitter asking for phages.
At the last minute, two came in
that looked like a match.(continued on page 66)