Healthy Skepticism Library item: 6277

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Publication type: news

Westphal S.
Tough Prescription : Heart Medication Approved for Blacks Faces Uphill Battle
Wall St Journal 2006 Oct 16
http://online.wsj.com/article_email/SB116096445875393515-lMyQjAxMDE2NjEwNzkxNjc0Wj.html

Full text:

Tough Prescription : Heart Medication Approved for Blacks Faces Uphill Battle
As Insurers Debate Costs And Generics Loom, BiDil Fails to Reach Needy
The Role of Medicare Part D
By SYLVIA PAGÁN WESTPHAL
October 16, 2006; Page A1

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 Pagán Westphal at sylvia.westphal@wsj.com