VPHM news was out on Saturday
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'Common Cold' Virus Drug Is Near
By DANIEL Q. HANEY AP Medical Editor
EXTON, Pa. (AP) - Certainly a cure for the common cold would be a big story all by itself.
But how about a medicine that also stops viral meningitis? The summer flu? Deadly newborn
infections? Even polio?
One drug that does all this is surprisingly close. It is called pleconaril, and if large-scale
testing turns out well, it could be in drugstores within a year.
Pleconaril (pronounced plah-CONN-ah-rill) is the latest in a short list of medicines that kill
viruses. This drug, in fact, blocks an entire category of them, a collection of 169 distinctly
different nasties that together cause more human disease than any other.
Almost as remarkable as what pleconaril does, however, is how it came to be. This drug
was not so much discovered as designed. Developers worked their way through 1,500
different versions of pleconaril before settling on the one now in human testing.
Once drug development was a kind of organized serendipity, screening thousands of
random compounds to see what happens. But over the past decade, a quiet series of
breakthroughs has transformed the way drugs are developed. Now scientists explore the
shape and innards of their target right down to the last molecule. Then they fashion chemical
monkey wrenches to throw into the works.
Pleconaril is the latest, and one of the most impressive, examples of this new way of creating
medicines. It is an exquisitely precise sort of monkey wrench. The drug fits neatly into a
groove on the surface of the virus, gumming up the machinery it needs to infect the body's
cells.
Experts believe the same research techniques will lead to treatments for many other kinds of
viruses, predators that are still mostly beyond the powers of modern medicine.
``Pleconaril represents a class of drugs that were designed with the knowledge of the
three-dimensional structure of the virus,' says Dr. Catherine Laughlin, chief of virology at the
National Institute of Allergy and Infectious Diseases. ``It provides a lot of hope for the
eventual design of drugs for virtually every viral infection.'
Pleconaril is made by ViroPharma Inc (NasdaqNM:VPHM - news)., a 5-year-old,
102-employee pharmaceutical firm in the Philadelphia suburbs. The publicly traded
company is sponsoring two large studies, due out in the spring, that will determine whether
the drug works well enough to win Food and Drug Administration approval.
The company wants to get the drug approved first for viral meningitis, but it is the common
cold - the most prosaic of infections - that is likely to be the medicine's biggest market.
``Everyone talks about the cure for the common cold,' says Dr. Jose Romero of Creighton
University in Nebraska, who has tested the drug on patients. ``This IS the cure for the
common cold.' Some might quibble over that word. ``Cure,' after all, implies that pleconaril
will make the sniffles evaporate instantly, which it won't. Still, the research indicates the
medicine can shorten a bad cold by three or four days and help people feel considerably
less miserable along the way.
Pleconaril does this by disabling the rhinovirus, the most common human virus. But that's just
the start.
It also neutralizes the second most common human virus, the enterovirus. Various versions
of enteroviruses cause an amazingly broad range of illnesses: lingering summer colds,
head-splitting meningitis, childhood fevers, inflammation of the heart, polio, plus
overwhelming infections that sometimes kill newborns.
One drug can stop both rhinoviruses and enteroviruses because they are close cousins,
members of a large family called the picornaviruses.
``There have been a number of anti-picornavirus agents over the past 25 years, but they've
had all sorts of problems,' notes Dr. Mark Pallansch, an enterovirus expert at the U.S.
Centers for Disease Control and Prevention. ``Pleconaril is the first true, viable product that
is potentially licensable.'
ViroPharma estimates that every year, Americans get between 400 million and 500 million
picornavirus infections that are serious enough to make them feel bad. It plans to charge
between $50 and $100 for enough medicine to cure one infection.
You do the math.
Certainly other drug makers have. However, only one other company appears to be close
to ViroPharma for now. Agouron Pharmaceuticals, a part of Warner-Lambert
(NYSE:WLA - news) Co., is experimenting this fall on 900 cold victims to see if its nasal
spray, code named AG7088, will speed their recovery. Agouron's drug is a protease
inhibitor, a lot like the ones that revolutionized AIDS treatment, but is intended only for
colds. And that ailment is the least of the reasons why many doctors are so enthusiastic
about pleconaril.
More than 2,000 people ranging in age from 84 to under a week have taken pleconaril.
Almost all of them have been in formal studies of viral meningitis or colds, neither of which is
a dire illness in otherwise healthy people.
However, enterovirus infections are occasionally medical emergencies. Over the past two
years, the FDA has allowed the company to dispense pleconaril outside of organized
experiments for infections that are life-threatening or especially gruesome.
So far, nearly 100 people have been treated this way, often with seemingly spectacular
results. Doctors say these back-from-the-almost-dead anecdotes offer some of the most
impressive hints of the drug's potency. Among the apparent success stories are Carter and
Skyler Stephens, twins born September 9, 1998 in Topeka, Kan.
Everything seemed fine until four days after their birth. The boys' mother, Lisa Stephens,
woke at 4 a.m. to nurse Carter. He wouldn't eat and had a boiling fever. The parents took
his temperature - a scary 104 - and raced to the emergency room. By then, Carter was
having trouble breathing.
Two hours later, he was flown to Children's Mercy Hospital in Kansas City. But things only
got worse. Now Skyler, who was also at the hospital with his mother, wouldn't eat, either.
Suddenly, he stopped breathing and had to be revived. So Skyler caught the next
evacuation flight to Kansas City, right behind his brother.
``My mom and I drove to Kansas City,' Mrs. Stephens remembers. ``That was on the
13th, the worst and longest day in the world.'
The problem eventually turned out to be overwhelming enterovirus infection. This is a
mercifully rare condition, but it can happen if a mother catches the virus late in pregnancy
and unknowingly passes it to her baby. Uncontrolled by the newborn's immature immune
system, the virus may eventually attack the liver, the heart and other organs. There has been
no treatment, and the death rate is high, somewhere between 40 percent and 80 percent.
For the next three days in intensive care, the babies' blood counts dropped, and they
received transfusions. Spinal taps found the virus in their central nervous systems. This was
especially worrisome, because there it can lead to brain damage.
Antibiotics, which kill bacteria, do nothing for viral infections. Then someone mentioned an
experimental antiviral drug that might help.
``I don't know how, but one of the doctors had heard of pleconaril,' says Mrs. Stephens.
``It was some sort of a miracle. On Wednesday they gave them the drug. The next day we
saw improvement. They were awake five minutes out of the whole day, but it was
improvement. Friday they were awake a little more, and Saturday they were taken off
oxygen.'
The next Monday, the babies were sent home, and ``since then, they are just perfectly
healthy, normal guys,' the mother says.
About two-thirds of the babies like these getting pleconaril have survived, even though many
were desperately ill before treatment started.
The drug has also been given to adults with defective immune systems who suffer enterovirus
brain infections that simply will not go away. The usual course is inexorably downhill.
Doctors say some of these people have fully recovered after a few days of pleconaril. Their
symptoms go away, leaving no trace of the virus.
Doctors have also successfully treated people with myocarditis, an inflammation that can
destroy the heart, and with polio, which is also caused by an enterovirus. Overall, doctors
estimate that about three-quarters of these emergency cases appear to have benefited from
pleconaril.
``Some of these patients had been ill for years, and they appeared to improve with seven to
10 days of treatment,' says Dr. Harley Rotbart of the University of Colorado Health
Science Center. ``Without overstating the results, I am very encouraged.'
Compelling as these cases are, they actually prove little about pleconaril's worth. Even the
sickest enterovirus victim may spontaneously recover. For proof, the FDA requires large,
carefully designed experiments to compare the medicine with standard care.
ViroPharma hopes first to prove that pleconaril cures viral meningitis. This common
infection, which doctors sometimes called aseptic meningitis, is an inflammation of the
covering of the brain and spine. Bacteria can also cause it, but vaccinations have made that
form of meningitis rare.
The CDC estimates that about 50,000 Americans are hospitalized each year with viral
meningitis, but perhaps 500,000 actually get it, many of them probably riding it out at home
without seeing a doctor.
Beyond painkillers, there is little a doctor can offer. Even though rarely fatal, this is a
miserable disease. Many feel desperately ill with pounding headaches, stiff necks, fever and
nausea.
Small studies on victims of viral meningitis certainly have looked promising. One of them
suggests the drug begins to ease headaches within a day. People felt completely back to
normal within seven days, compared with nine days in those getting dummy pills.
The results of two large meningitis studies on adults and adolescents are expected in the
spring. If they turn out as ViroPharma hopes, research director Mark A. McKinlay says, the
company will immediately seek approval to sell the drug. With a speedy FDA review, this
could put a liquid form of pleconaril on the market by the end of 2000.
Next would come a pleconaril pill, intended for treating colds, that the company hopes to
sell in 2001. ViroPharma estimates Americans make between 30 million and 36 million
doctor visits a year for colds, making this the most common medical complaint doctors hear.
But the fact is, doctors can do nothing for the common cold.
Not that this stops them from trying.
Estimates vary, but doctors prescribe antibiotics for perhaps half of all cold victims they see.
These drugs will not cure colds. Except in the rare cases where people have bacterial
complications, they do nothing to ease the symptoms. They are just expensive placeboes.
Yet one recent study found that 12 percent of all antibiotic prescriptions for children are for
colds.
All of this suggests that if pleconaril actually does something to ease a cold, it will be avidly
prescribed. The results of cold studies so far suggest it may truly help.
In the first of these, doctors intentionally infected intrepid volunteers with coxsackie virus, a
kind of enterovirus that causes an especially obnoxious cold. Treatment began the day
before they were exposed to the bug. Thirteen percent on pleconaril developed colds,
compared with 65 percent taking dummy pills.
Researchers actually weighed the volunteers' nasal drippings. The averages: 10 grams of
gook daily for the unlucky placebo folks, one gram for those taking pleconaril.
This was the first evidence that a medicine could change the course of a cold. But it was
hardly a fair test. After all, most people will not take drugs in advance to ward off a cold.
So Dr. Frederick G. Hayden of the University of Virginia tested pleconaril's effects on
victims of garden-variety sniffles. Just over 1,000 who went to doctors with fresh colds
agreed to be randomly put on pleconaril or placeboes. |
