Pulse of Progress?
New drugs aim to improve the treatment of high blood pressure by
attacking it in novel ways
By ANITA GREIL
Staff Reporter of THE WALL STREET JOURNAL
October 10, 2005; Page R4

Of all the people being treated for high blood pressure in the U.S.,
it's estimated that only about one-third of them have it under control.

That alarming statistic is one reason doctors and researchers are
scrambling to improve the treatment of high blood pressure, or
hypertension, a potentially life-threatening condition that puts
sufferers at risk for heart disease, stroke, kidney problems and other
serious diseases.
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While numerous drugs are available to treat high blood pressure, none
of them is perfect. Some can be slow to work, while others disappear
from the body too quickly. For most patients, no one of these drugs on
its own brings blood pressure down to target levels.

As a result, more and more doctors are treating hypertension patients
with a combination of drugs, trying to find the most effective mix for
each individual. And researchers are developing drugs that attack
hypertension in new ways. Two promising new drugs under development,
Novartis AG's SPP100 and Myogen Inc.'s Darusentan, are still 18 months
or more away from regulatory approval, but researchers say the drugs
have the potential to improve hypertension care.

Blood pressure is the force in the arteries when the heart beats
(called systolic pressure) and when the heart is at rest (diastolic
pressure). Blood pressure is too high if the systolic reading is 140
or higher or the diastolic pressure is 90 or higher.

Although narrowed arteries and other factors can contribute to high
blood pressure, in the vast majority of patients the cause is unknown.
It's unclear whether there is a genetic component. Hypertension runs
in some families, but that may be as much a result of shared
lifestyles as of shared genetic backgrounds. Being overweight,
drinking too much alcohol and eating too much salt raise the risk of
having high blood pressure.

Often there are no obvious symptoms, which is one reason the condition
commonly goes unnoticed for years. The results can be devastating. The
World Health Organization estimates that around 7.1 million people die
each year due to complications from hypertension.

Doubling Up

Current drug therapies for hypertension include diuretics, or water
pills; beta blockers; and angiotensin-converting enzyme (ACE)
inhibitors, which are all available generically. Newer medicines
include angiotensin II receptor blockers (ARBs), such as Diovan and
Cozaar, and calcium channel blockers such as Norvasc. Diuretics, beta
blockers and calcium channel blockers lower blood pressure by reducing
the strength and rate of the heartbeat. The ACE inhibitors and ARBs
prevent the production of chemicals in the kidney that can raise blood
pressure. None of the drugs has ever been proved to be significantly
more effective than another, says Jessica Mann, a cardiologist and the
medical director at Speedel, a Swiss start-up pharmaceutical company
that did the early research on SPP100 before licensing the drug for
further testing to Novartis.

One problem with the currently available treatments is that most
patients don't reach the desired blood-pressure levels with one
medication. "When you are diagnosed with high blood pressure, you are
lucky if the first drug prescribed has the right mode of action to
lower blood pressure below target," Dr. Mann says.

As a result, it's becoming more common for physicians to prescribe
combinations of two or more drugs, typically including a diuretic, the
oldest type of hypertension drug, says Thomas Pickering, head of the
Behavioral Cardiovascular Health and Hypertension Program at the
Department of Medicine at Columbia University in New York. It appears
that the best results generally are being achieved by combining an ACE
inhibitor or ARB with a drug that works in another way, Dr. Pickering
says. Drug companies have caught on to the trend and increasingly are
producing treatments that combine drugs in a single pill.

New Treatments Ahead

Meanwhile, researchers hope patients can get better results with two
new drugs now under development. SPP100 is the first in a new class of
hypertension drugs called renin inhibitors. Renin is an enzyme that
controls the formation of a substance called angiotensin II, the key
mediator in the regulation of body fluid volume and blood pressure.

Although ACE inhibitors and ARBs all affect levels of angiotensin II,
Novartis says SPP100 does it in a way that has the potential to be
more effective than existing treatments. The drug recently completed
clinical tests required before any new treatment can be submitted to
the Food and Drug Administration for review. The tests showed that
SPP100 significantly lowered blood pressure and that lower levels were
maintained for 24 hours. Novartis plans to file early next year for
FDA approval to market the drug in the U.S.

The staying power of SPP100 could be a significant benefit, some
experts say. A common complication of treatment for high blood
pressure is that the effect of medication wears off within hours. As a
result, patients often aren't protected when they need protection
most: early in the morning, when blood pressure is highest. Indeed,
most strokes happen in the early morning, Dr. Mann says.

However, physicians like Dr. Pickering maintain that around-the-clock
protection can also be achieved with existing medications by simply
splitting up a day's worth of drugs into two doses.

Another drug candidate that aims to lower blood pressure in a novel
way is Myogen's DAR201, or Darusentan, which has proved to cause
significant drops in blood pressure in patients for whom other drugs
don't work. The compound is about a year behind SPP100 in clinical
development and could become available by 2008.

Darusentan promises to be the first in a class of drugs called
endothelin receptor antagonists, or ERAs. The drug works by blocking a
hormone called endothelin, which is believed to play a critical role
in the control of blood flow and cell growth. Because Darusentan
blocks the constriction of blood vessels, and therefore works
differently from currently available drugs, scientists hope it can
work for those patients whose blood pressure can't be successfully
reduced to target levels even if they are taking three or more
hypertension treatments.

There is one problem with treating high blood pressure, though, that
can't be overcome with any combination of drugs or new treatments:
Hypertension patients are particularly prone to neglecting to take
their medication.

Because high blood pressure usually has no symptoms, there's no
discomfort or disability to remind patients of the importance of their
medication. And the penalty for not taking the pills often is years
away, which can make it difficult for many people to be conscientious
about their treatment.

There's little physicians can do about this problem, except to try to
convince patients of the gravity of the issue. Dr. Pickering has one
suggestion: Patients who are told to monitor their blood pressure
daily, he says, can at least see the results of their treatment, and
might be more likely to stick to their regimen.

--Ms. Greil is the bureau chief for Dow Jones Newswires in Zurich.

Write to Anita Greil at anita.greil@...