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 But when a drug already taken by thousands of people for intestinal
conditions appeared to control the monkey version of HIV, it got the
attention of the director of the National Institutes of Allergy and
Infectious Diseases.
Fauci hopped on a plane to Cambridge, Mass., to personally tell
Japan's Takeda Pharmaceutical Co's U.S. representatives that their
drug may offer a dramatic advance in the fight against AIDS.
Takeda’s drug suppressed the virus to undetectable levels in eight
monkeys, some for two years. The findings raise hopes for a
so-called "functional cure" – a treatment that puts the disease in
sustained remission.
"The data was so dramatic," said Fauci, who has made AIDS research
his life’s work.
The drug is one of several promising ideas heading into early-stage
human trials, all seeking to help patients control the virus that
causes AIDS for extended periods without daily antiretroviral
therapy (ART).
The studies build on research propelled by the case of Timothy Ray
Brown, the so-called "Berlin patient," whose HIV was eradicated
through an elaborate stem cell transplant in 2007.
"There has been this explosion of discovery," said Mitchell Warren,
executive director of the AIDS Vaccine Advocacy Coalition. "There
are completely new ideas that were impossible to conceive even a few
years ago."
LIMITS OF CURRENT DRUGS
HIV once meant certain death. But, for more than half of the 36.7
million HIV patients around the world, ART transformed it into a
chronic disease.
Taken daily, ART suppresses the virus. But keeping up a daily
medication regimen is difficult. The drugs are expensive and toxic,
causing nausea, fatigue and nerve problems in the short-term, and
insulin resistance and other problems over time.
Only about a third of U.S. patients take ART consistently enough to
push the virus down to undetectable levels.
“We're going to need other approaches," said Dr. Nelson Michael,
director of the U.S. Military HIV Research Program at the Walter
Reed Army Institute.
Much work has focused on the discovery of rare antibodies made by
HIV patients that can neutralize several different forms of the
virus. One trial involving an antibody called PGT121 licensed by
Gilead Sciences Inc reduced the virus to undetectable levels in 16
of 18 monkeys; the effect lasted for four months in three of them.
At Walter Reed, Michael is taking a different tack, testing whether
a vaccine - being developed to prevent HIV infection - can fight off
the virus in infected individuals.
Last month, Michael and researchers at Harvard's Beth Israel
Deaconess Medical Center published the results of a monkey test of
Johnson & Johnson's HIV vaccine candidate called Ad26/MVA and
Gilead's experimental drug GS-986.
On its own, the vaccine had a modest effect. But it was even more
effective when it was given with GS-986, a so-called TLR-7 agonist
that “kicks the immune system up to a higher gear,” Michael said.
All nine monkeys that got both treatments showed significantly
reduced viral loads. In three, the combination therapy has kept the
virus at bay for at least six months.
Human trials could begin within months, said Dr. Paul Stoffels,
J&J's chief scientific officer.
"If the cure is there, the industry will find a way to get there
very quickly," Stoffels said.
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"IT WAS LIKE, 'WOW"
Fauci’s visit was a first for Takeda, a company focused on
treatments for cancer, gastroenterology and the central nervous
system, said Dr. Michael Shetzline, who heads clinical science for
Takeda in Cambridge.
“The excitement was just clear,” Shetzline said. “It was like,
'Wow.'"
Takeda does not study HIV. But its researchers understood the basic
science surrounding its drug Entyvio, an antibody engineered to
attack a specific protein.
The drug, known generically as vedolizumab, is approved in more than
50 countries for ulcerative colitis and Crohn’s disease, which occur
when the immune system attacks the intestines.
"Entyvio is a cell trafficking molecule that affects immune
responses," Shetzline said. "In this instance, the GI tract is what
is harboring this HIV cell population that needs to be cleared - at
least that is what the monkey study implies."
Takeda is providing the drug and supporting the study. Shetzline
cautioned that it's only a pilot.
"We'd love to see this benefit patients,” he said.
If it pans out, cost could be an issue. Entyvio is priced as a
biologic, similar to other IBD treatments, which range from $2,000
to $5,000 a month, according to Consumer Reports.
Entyvio's HIV trial began in August and seeks to enroll 15 to 25
people with stable disease. They will remain on daily ART drugs
while taking nine infusions of Entyvio over a period of several
months. Then, ART will be stopped, they will get two more infusions,
and doctors will watch to see if the virus rebounds – or remains
suppressed.
Manni Baez, 30, of Columbus, Ohio, travels to the National
Institutes of Health in Bethesda, Maryland, about once a month for
the study.
“For me, the end game is providing the folks at NIH with the
resources they need to get them closer to finding a cure or a
vaccine for this plague," Baez said.
Fauci said he doesn’t expect meaningful results until late 2017 or
early 2018. Even partial success would be huge, he said.
"If we discontinue therapy in the 15, and four of them don't
rebound,” he said, then “that is the best anybody has ever seen.”
Fauci said he doesn’t get emotional about the data he collects, and,
in any event, it’s early days for this research.
“I try to be as objective as I possibly can,” he said. “I will get
really excited if we get our first seven people in human (trial),
and I stop ART - and they don't rebound.”
(Reporting by Julie Steenhuysen; Editing by Michele Gershberg and
Lisa Girion)
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