[Ip-health] Tough Prescription : Heart Medication,Approved for Blacks Faces Uphill Battle

[Joana Ramos]

Tough Prescription
Heart Medication
Approved for Blacks
Faces Uphill Battle

<snip>

> Skeptics say that NitroMed has failed to prove that its drug is more
> effective than the available generics. This summer, the Centers for
> Medicare & Medicaid Services asked the American Heart Association and
> the American College of Cardiology for guidance on the matter. In a
> joint response, the groups said that they viewed the use of either the
> generics or BiDil as "reasonable" for the management of heart failure
> in blacks and in accordance with current treatment guidelines. "We
> consider them to be equivalent," says ACC president and Cleveland
> Clinic cardiologist Steven Nissen.
>
> Compared with the generics, "there is nothing magical" about BiDil,
> adds Bernie Good, chairman for the medical advisory panel that
> oversees drug coverage for the Department of Veterans Affairs. The VA
> has decided not to provide BiDil coverage in its national formulary --
> the list of drugs preferentially offered to veterans covered by its
> health plans. The generics are widely available to beneficiaries.
<snip>

> NitroMed, meanwhile, is taking a hardball stance. It says it believes
> insurers that encourage the prescription of the two generic drugs
> instead of BiDil may be bordering on patent infringement. That's
> because the company owns several patents covering the combination use
> of isosorbide and hydralazine, either as separate pills or in a single
> pill, for the treatment of heart failure. The company has sent letters
> to more than a dozen health insurance plans, including Aetna Inc.,
> Humana Inc. and Coventry Health Care Inc., placing them on notice of
> this view.


As Insurers Debate Costs
And Generics Loom,
BiDil Fails to Reach Needy
The Role of Medicare Part D
By SYLVIA PAG=C1N WESTPHAL
October 16, 2006; Page A1

(copied as fair use)
http://online.wsj.com/services/article/SB116096445875393515-search.html?KEY=
WORDS=3Dbidil&COLLECTION=3Dwsjie/6month


In June 2005, the Food and Drug Administration made history by approving
the first drug authorized for use in a single racial group.

The drug, BiDil, was cleared to treat congestive heart failure
exclusively in African-Americans. A clinical trial sponsored by NitroMed
Inc., the drug's maker, showed that within a year of usage, BiDil
reduced deaths by 43% among black patients who had tried other
medicines. It worked so well that an independent advisory board deemed
it unethical to deny the drug to trial participants who, for comparison
purposes, had been taking a placebo.

Yet after more than a year on the market, BiDil is reaching only about
1% of the 750,000 African-Americans who suffer from heart failure.
[Chart]

Sluggish acceptance for a new drug is not unusual. But BiDil's rollout
sharply illustrates how the interests of patients, insurers and drug
companies can easily collide. In this case a company's decision to price
a drug steeply, resistance by insurers, and a change in federal policy
all proved to be impediments. The drug's unavailability, say some
medical experts, may also be symptomatic of a deeper problem in the
health-care system, where issues affecting minorities and the poor
sometimes fall through the cracks.

African-Americans are especially vulnerable to congestive heart failure,
a condition in which the heart fails to pump sufficient blood and
progressively weakens. The prevalence of the disease among blacks aged
45 to 64 is about 5%, almost double that of whites. Blacks with the
ailment also deteriorate more rapidly than white patients do.

Several studies have shown that, compared with whites, blacks with heart
disease are also less likely to receive services and treatment for it.
An analysis by Amundsen Group, a consulting firm specializing in managed
care issues, estimates that roughly 70% of all African-Americans over
the age of 45 have no health-insurance coverage for BiDil or must pay
steep insurance co-payments to obtain the drug.

One reason BiDil isn't being more widely prescribed is price. The U.S.
Department of Veterans Affairs calculated the annual cost for BiDil to
be between $1,382 and $2,765 per patient -- sums not covered by many
insurance plans. The drug has also been caught up in a dispute about
generic alternatives. BiDil is a so-called combination drug made up of
two chemicals, isosorbide dinitrate and hydralazine. Both are available
in generic forms. Many insurers contend that BiDil is no more effective
than the cheaper generics taken separately.

NitroMed Chief Executive Jerry Karabelas says that the price for BiDil
is in line with the value that it brings to patients. He also insists
that the generics are not equivalent.

But the vast majority of blacks with heart failure aren't getting either
treatment -- branded or generic. "This is a therapy that's being
underutilized," says Wilson Colucci, chief of cardiovascular medicine at
Boston University Medical Center. He says many doctors aren't well
enough educated about treatments for heart failure.

A Big Problem

Other doctors say that a big problem with the generics is that they
involve a complex regimen. To achieve the same dosage of one BiDil pill,
a patient would have to take one pill of generic isosorbide, along with
one and a half tablets of hydralazine, the other generic, three times a
day. Because the generics come in many different doses the combinations
can vary greatly, making it hard for patients -- many of them seniors
taking multiple drugs.

Many black Americans who were formerly eligible to receive BiDil under
Medicaid -- the state-administered insurance program for the poor --
lost their ability to get the drug when Medicare Part D became effective
in January. Part D was designed to expand drug coverage for the elderly.

But under a little-known provision, patients eligible for both Medicare
and Medicaid were required to give up their Medicaid drug benefits and
accept a Part D plan randomly assigned to them. Among these is an
estimated group of tens of thousands of African-Americans with heart
failure who ended up with plans that didn't cover BiDil.

Jeffrey Kelman, a senior officer at the Centers for Medicare & Medicaid
Services, says every Medicare Part D plan "has BiDil, the generic
components or both" on its list of covered drugs.

Dr. Karabelas, NitroMed's chief executive, says the company issues
discounts for health insurers that bring the price of the drug down to
levels "competitive" with other popular branded heart drugs.

One patient who lost her BiDil coverage was 79-year-old Victoria Smith,
a former nurse's aid in Cheraw, S.C. Her cardiologist prescribed BiDil
last year, and she paid just $2 to $3 a month for the drug via Medicaid.
Ms. Smith, who lives on a fixed income of $873 a month, says the drug
improved her symptoms, giving her more energy. But after she was moved
to a Medicare Part D plan this year, she was no longer covered for the drug=
.

"She found out by calling the pharmacy to get the medication refilled,
and they told her it wasn't covered," says her son Jerome Smith. "That's
a major concern. She can't afford to pay for BiDil."

For now, Ms. Smith's doctor is providing her with free samples, but she
worries about the day when they run out. "Without my heart I wouldn't be
here, so I would have to sacrifice something else," she says.

Such stories anger some NitroMed allies. "If that were white patients,
nobody in America would tell them, 'Excuse me, I want you to go buy a
drug for angina and another for hypertension, and I want you to go home
and cut them, and I want you to take multiple pills a day on top of all
the [other drugs] you got,' " says Gary Puckrein, a NitroMed shareholder
and executive director of the National Minority Health Month Foundation,
a nonprofit organization that has received educational grants from the
company. If the medical establishment "were doing it to whites there
would be an uproar," he says.

Skeptics say that NitroMed has failed to prove that its drug is more
effective than the available generics. This summer, the Centers for
Medicare & Medicaid Services asked the American Heart Association and
the American College of Cardiology for guidance on the matter. In a
joint response, the groups said that they viewed the use of either the
generics or BiDil as "reasonable" for the management of heart failure in
blacks and in accordance with current treatment guidelines. "We consider
them to be equivalent," says ACC president and Cleveland Clinic
cardiologist Steven Nissen.

Compared with the generics, "there is nothing magical" about BiDil, adds
Bernie Good, chairman for the medical advisory panel that oversees drug
coverage for the Department of Veterans Affairs. The VA has decided not
to provide BiDil coverage in its national formulary -- the list of drugs
preferentially offered to veterans covered by its health plans. The
generics are widely available to beneficiaries.

With insurance plans balking, BiDil's sales of $5.2 million in the first
half of this year were significantly below analysts' prelaunch
estimates, which had the drug achieving around $130 million in sales for
2006. NitroMed's stock has plummeted to under $3 from about $23 a share
at the time of the launch of BiDil, its only product on the market. Last
week, the Lexington, Mass., company announced a major restructuring,
which involves significantly shrinking its sales staff.

Difficult Path

BiDil traveled a difficult path to the market. Jay Cohn, a cardiology
professor at the University of Minnesota, first had the idea of
combining the two chemicals found in BiDil in the mid-1970s. Both drugs,
isosorbide and hydralazine are vasodilators -- that is, they act to
expand vessels, allowing more blood to flow through them.

In 1980 and 1986 Dr. Cohn led two trials, of 642 and 804 patients
respectively, that tested the drugs in heart-failure patients. The
studies found evidence that the combination of drugs improved survival
rates. The results, though, were barely statistically significant and
not enough to convince the FDA to approve the therapy. At the time, the
company seeking approval was Medco Research Inc., which had licensed Dr.
Cohn's patent for BiDil.

A later review of the trial data by Dr. Cohn showed that a subset of
African-Americans had benefited to a greater degree than whites. The
reasons for that still aren't clear but may be related to genetic
differences in the production of nitric oxide, a molecule produced by
the body that helps the heart function better and which BiDil is
presumed to protect.

In 1999, Dr. Cohn licensed his patents to NitroMed, a biotech company
founded in 1992 that had been exploring therapies based on nitric oxide.
In 2001 a new trial of BiDil was started, but was restricted to black
patients taking all other drugs available for heart failure.

The drugs and dosing ratios remained the same as in the older studies
but were combined into a single pill, taken three times a day. The trial
showed that four lives were saved and eight hospitalizations avoided
annually for every 100 patients taking BiDil compared with a placebo, or
dummy pill. The drug received FDA approval in the summer of 2005.
Although it is officially sanctioned for use only among blacks, doctors
can prescribe BiDil "off-label" for any patient.

Since BiDil's approval, insurers and others have supported the generic
alternative by citing the earlier trials -- those that showed benefits
when the two drugs were tested in the general population.

NitroMed's CEO, Dr. Karabelas, disputes the insurers' argument. He says
that the research data submitted to the FDA by Medco shows that
isosorbide and hydralazine pills taken separately don't produce the same
blood levels of the active ingredients as taking the single pill form.
The two drugs aren't approved separately to treat heart failure and
aren't considered generic versions of BiDil by the FDA, he notes. In
May, the agency issued a letter stating that it "has not approved any
drug product...that is designated as therapeutically equivalent (i.e.,
substitutable) to BiDil."

NitroMed, meanwhile, is taking a hardball stance. It says it believes
insurers that encourage the prescription of the two generic drugs
instead of BiDil may be bordering on patent infringement. That's because
the company owns several patents covering the combination use of
isosorbide and hydralazine, either as separate pills or in a single
pill, for the treatment of heart failure. The company has sent letters
to more than a dozen health insurance plans, including Aetna Inc.,
Humana Inc. and Coventry Health Care Inc., placing them on notice of
this view.

"We'd much rather have the plans as our customers and we don't want to
be litigants," says company spokeswoman Jane Kramer. "But if it becomes
necessary to fight for our intellectual property, we will."

Aetna replied that it was "very confident that our actions do not
violate any patent rights." A spokeswoman for Humana said she had not
been able to find a record confirming receipt of the letter at the
health plan. Coventry didn't return several requests for comment.

Write to Sylvia Pag=E1n Westphal at sylvia.westphal@wsj.com

--
Joana Ramos, MSW
Cancer Resources & Advocacy
7303 23rd Ave. NE
Seattle, WA  98115
206-229-2420
http://ramoslink.info/