Drug Targets Faulty Process That Drives Cystic
WEDNESDAY, Nov. 17 (HealthDay News) -- A new drug focused on the
underlying cause of cystic fibrosis is showing promise in Phase II
clinical trials, new research shows.
If eventually approved by the U.S. Food and Drug Administration,
the drug known as VX-770 would mark the first treatment that gets
at what goes wrong in the lungs of people with cystic fibrosis,
rather than just the symptoms.
Only 4 to 5 percent of cystic fibrosis patients have the
particular genetic variant that the drug is being studied to treat,
according to the study.
But Robert Beall, president and CEO of the Cystic Fibrosis
Foundation, said VX-770 is only the first in a new class of drugs,
some of which are already in the pipeline, that may work in a
similar way in people with other cystic fibrosis-linked gene
"There has never been such a sense of hope and optimism in the cystic fibrosis community," Beall said. "This is the first time there's been a treatment for the basic defect in cystic fibrosis. If we can treat it early, maybe we won't have all the infections that destroy the lungs and eventually takes people's lives away."
The study appears in the Nov. 18 issue of the
New England Journal of Medicine.
Cystic fibrosis is a progressive, inherited disease affecting
about 30,000 U.S. children and adults. It is caused by a defect in
the CF gene, which produces the CFTR (cystic fibrosis transmembrane
conductance regulator) protein, which is important in the transport
of salt and fluids in the cells of the lungs and digestive
In healthy cells, when chloride moves out of cells, water
follows, keeping the mucus around the cell hydrated.
However, in people with the faulty CFTR protein, the chloride
channels don't work properly. Chloride and water in the cells of
the lungs stay trapped inside the cell, causing the mucus to become
thick, sticky and dehydrated.
Overtime, the abnormal mucus builds up in the lungs and in the
pancreas, which helps to break down and absorb food, causing both
breathing and digestive problems.
In the lungs, the accumulation of the mucus leaves people prone
to serious, hard-to-treat and recurrent infections. Overtime, the
repeated infections destroy the lungs.
The average life expectancy for a person with cystic fibrosis is
about 37, according to the Cystic Fibrosis Foundation.
While inhaled antibiotics and other treatments have led to
substantial improvements in life expectancy, no treatments
specifically target the CFTR protein. That's where VX-770 comes in,
said Dr. Frank Accurso, lead study author and a professor of
pediatrics at University of Colorado Denver and The Children's
Hospital in Denver.
With $76 million in funding from the Cystic Fibrosis Foundation,
Vertex Pharmaceuticals screened hundreds of thousands of molecules
in the lab, searching for those that might work to alter the
chloride channels in cystic fibrosis cells.
"You can think of the gate as being closed," Accurso said. "What this treatment does is open up the gate, allowing the chloride channel to open and the water to get out."
In the Phase II trial, 39 adults with cystic fibrosis took
either the drug or a placebo for two weeks, and then again for 28
days. All patients had the G551D mutation, present in 4 to 5
percent of patients, according to the study.
Tests showed that not only did lung function improve,
participants reported feeling better.
Levels of chloride in sweat also fell, indicating the drug is
working on the cellular level to better regulate the release of
"That is telling us that we have improved the function of the CFTR," Accurso said.
The primary objective of the study was to evaluate the safety
and tolerability of the drug. There was no difference in the
frequency of reported adverse events among those taking the drug
vs. the placebo. The six severe adverse events reported -- macular
rash in one person and, in another person with diabetes, elevated
glucose levels -- were resolved without discontinuing the drug.
In a journal editorial, Dr. Michael J. Welsh wrote that the
research represented "a milestone along the pathway of discovery
leading to better preventions, treatments and cures," although he
cautioned that "more studies involving more patients and longer
test periods are needed to test the safety and efficacy" of the
Phase III trials of VX-770 are expected to wrap up early in
2011, according to Vertex company spokesman Zach Barber. He said
that Vertex will likely apply for FDA approval in the latter part
While VX-770 is promising, it may be only the first of a new
class of drugs, Beall said. Phase II trials for another molecule to
treat people with the DF508 mutation, the most common cystic
fibrosis mutation (present in about half of people with the
disease), are ongoing, Beall said.
"We are so confident in this approach we are already starting to think of the next generation of small molecules to improve upon these compounds, Beall said. "We know we're on the right pathway."
Foundation has more on the disease.
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