Viagra Gains Some Advocates as Treatment for Lung Disease

April 10, 2004
By ANDREW POLLACK

 NYTimes.com




Diane Adkins, who has a life-threatening lung disease, used
to take a drug that cost more than $100,000 a year and that
had to be pumped round the clock into a vein through a hole
in her chest. Now she has replaced it with a pill that
costs about $10,000 a year.

But her insurance company will not pay for the cheaper
drug, even though it paid for the more expensive one. As
the company explained in a letter, "Your benefit program
covers this medication for men over the age of eighteen
(18) only."

The drug is Viagra. Wisecracks aside, the blue pill that
treats erectile dysfunction, a common but less than fatal
male malady, may have a new role in treating pulmonary
hypertension, a rare but deadly disease that afflicts
mainly women.

Results of a clinical trial in India, published this week
in The Journal of the American College of Cardiology,
showed that Viagra increased the ability of patients to
exercise by about 40 percent. The authors said that was
greater than the effect seen with other drugs in different
trials. Although the trial involved only 22 patients, it
was the first randomized test to compare Viagra against a
placebo for pulmonary hypertension, the journal said.

Pfizer, the manufacturer of Viagra, said it expected
results of its own much larger and more definitive trial
around the middle of the year. Investigators expect to
present results at the American Heart Association's annual
meeting in November.

But because doctors are allowed to prescribe a drug for any
use, once it wins regulatory approval, some are already
using Viagra for pulmonary hypertension. The drug is even
being given to babies.

"I thought it was a joke," said Drew Walen of Nashville,
recalling his reaction when a doctor told him to give the
drug daily to his infant son, George, whose lungs did not
develop properly because of a congenital problem.

Pulmonary hypertension is different from hypertension, the
common condition of high blood pressure. The pulmonary
disease involves extremely high pressure in the artery that
carries blood from the heart to the lungs to pick up
oxygen. The disease, also called pulmonary arterial
hypertension, can make even routine tasks an ordeal.

"I got to the point where I couldn't change my clothes
without getting out of breath," said Ms. Adkins, a 48-year
old vice president at a floor-covering company who lives in
Jensen Beach, Fla.

For Pfizer, approval of Viagra as a treatment for pulmonary
hypertension could ease some of the criticism that drug
companies focus too much on so-called lifestyle drugs. In a
small way, it could help buttress Viagra sales as new
competitors eat into the market for impotence medications.
It also might help Pfizer extend the patent protection on
the drug.

Some doctors and insurance companies say they have concerns
about this use of Viagra, saying it has not been proved
effective in rigorous clinical trials, whereas other drugs
have. Patients with pulmonary hypertension use the drug
every day and in higher doses than men who use it before
sex, potentially raising new risks.

"I have some ethical issues in using an experimental drug
in place of an approved drug," said Dr. Richard Channick of
the University of California, San Diego, who said Viagra
was being overused. Dr. Channick is a consultant to
Actelion, a Swiss company with an approved drug for the
disease.

Robert Wanovich, manager of clinical services at Highmark,
Ms. Adkins's insurer, said Viagra was not covered because
it had not been proved to work for pulmonary hypertension.
He conceded, however, that because insurance claims do not
specify how a drug is being used, a man using Viagra for
the lung disease could be reimbursed "and we would never
know."

Though only about 100,000 people in the United States and
Europe have pulmonary hypertension, three drugs have
already been approved for the condition and several others
are on the way. Executives attribute the high degree of
competition for treating such a rare disease to two
factors. First, the disease has become better understood.
And second, if a drug has a high enough price and is taken
every day, sales can reach several hundred million dollars
a year, even in a small group of patients.

"A patient population that looks like 100,000 has the
equivalent economic value of a million patients or more,"
said Dr. Bruce D. Given, chief executive of Encysive
Pharmaceuticals, which is developing a drug for the
disease.

Roland Haefeli, spokesman for Actelion, said the patient
population might grow because doctors, who often miss the
condition, are looking more carefully now that treatments
are available.

Though far from cures for pulmonary hypertension, the new
drugs have helped improve the outlook for patients.

"In 1999, what I would have said to you is that 50 percent
of patients die within two years of diagnosis," said Rino
Aldrighetti, president of the Pulmonary Hypertension
Association, a patient group. "Now we are looking at five
years."

Some doctors say they prescribe Viagra because it has
worked in small trials, is generally safe and can be
cheaper than the approved drugs.

"We've used it a lot empirically, and it does work," said
Dr. Robyn J. Barst, an expert on pulmonary hypertension at
Columbia University and a lead investigator in the Pfizer
trials.

Pfizer said it would sell a pulmonary hypertension drug
under a different name and in a different form from Viagra
to prevent prescription errors. Investigators in the
clinical trials said the drug was being provided as a round
white pill, not a blue diamond-shaped one, and in doses
different from those used for erectile dysfunction.

Joel W. Morris, a Pfizer spokesman, said the company had
not decided whether the pulmonary drug would sell for a
higher price than Viagra, known generically as sildenafil
citrate.

Pulmonary hypertension is the only new use for which Pfizer
is testing the drug. The company recently dropped tests on
Viagra for female sexual dysfunction, a potentially huge
market, after results were disappointing. Viagra, which had
worldwide sales last year of $1.9 billion, faces
competition from two new drugs for erectile dysfunction,
Cialis and Levitra, which together claim a third of new
prescriptions in the United States.

Given the small patient population, sales of Viagra for
pulmonary hypertension are not expected to be that big for
Pfizer. Mr. Morris, the Pfizer spokesman, said the company
was pursuing the lung disease treatment because there was
an unmet medical need and because the company had been
urged to do so by doctors, who had begun testing the drug
on their own.

But he conceded that under American law, the company might
get a longer respite from generic competition for Viagra
because it was testing the drug in children, something that
can be done for pulmonary hypertension but not for erectile
dysfunction.

The first drug approved for pulmonary hypertension, in
1995, was Flolan, a version of a natural hormone called
prostacyclin, which dilates constricted blood vessels. It
is made by GlaxoSmithKline.

Flolan, which was also the first drug Ms. Adkins took for
her condition, disappears from the body so fast that it
must be pumped in 24 hours a day. The catheter used poses a
risk of infection, and users must carry a small pump and
mix a fresh batch of the drug every day.

The annual cost, roughly $100,000, can also be a hardship.
Merle Reeseman of Grove City, Pa., said that when her
insurer would not pay for Flolan, she had to separate from
her husband of more than 30 years to qualify for Medicaid,
which pays for the drug.

"The only way they would allow it was if I basically became
destitute," she said. "This just isn't fair."

Another of the new drugs, Remodulin, is a form of
prostacyclin infused under the skin rather than through a
catheter. That method lowers the infection risk, but many
patients complain of pain. The drug was approved in 2002,
and sales were $45.1 million last year. The developer,
United Therapeutics of Silver Spring, Md., estimated that
about 450 Americans were taking Remodulin at the end of
2003, versus about 2,550 taking Flolan.

CoTherix of South San Francisco, Calif., said it planned to
apply to the F.D.A. this year for approval of an inhaled
form of prostacyclin already sold in Europe by Schering.

The first oral drug, approved in 2001, was Tracleer from
Actelion; it inhibits endothelin, a hormone that helps
constrict blood vessels. Sales in 2003 were 300 million
Swiss francs, or about $235 million.

Though much cheaper than the two other approved drugs,
Tracleer still costs about $35,000 a year and can cause
liver problems, so users must have their liver enzymes
checked every month.

Encysive, based in Houston, and Myogen, based in
Westminster, Colo., are developing pills that they hope
will inhibit endothelin more effectively than Tracleer.
Encysive's drug, sitaxsentan, is well into the final stage
of testing while ambrisentan from Myogen has just entered
that stage.

Viagra works by yet another mechanism, inhibiting an enzyme
called phosphodiesterase 5. The drug relaxes blood vessels,
allowing blood to flow into the penis - or, it is hoped,
into the lungs.

Such a use would be a return to Viagra's roots. The drug
was originally tested for angina, a cardiovascular
condition, and proved disappointing. But some men in the
trials reported a side effect: erections.

Dr. Michael McGoon of the Mayo Clinic said the approved
drugs typically allow someone who cannot climb even one
flight of stairs to climb a flight or more, but "don't
return anybody to what they would perceive as normal
health."

Results with Viagra are "extremely variable," he said,
adding, "It's not a miracle."

Viagra, Dr. McGoon said, may be as effective as other drugs
but at a lower cost. Some experts said it was likely that
different drugs would be used in combination.

But Ms. Adkins swears by Viagra. She said she had spent
$5,000 on the drug and had hired a lawyer to press her
insurer to pay. "I told them I was going to get a sex
change," she said. "They would probably pay for the sex
change."