In the world of pharmaceuticals, a “blockbuster” is the term reserved for a prescription drug which has annual sales in the billion-dollar plus range (with the emphasis on “plus”).
While annual sales in the $500 million range are nothing to sneeze at, the many drugs that attain that level are looked upon as revenue producers. The blockbusters are looked upon as king-makers.
Thus, when drug has the potential to attain the elusive “10-figure” status, some very questionable marketing strategies take place. These include:
• Failing to disclose or report negative test or clinical trial results;
• Failing to report adverse reactions;
• Failing to finalize post-approval testing or reporting;
• Spending more on advertising a drug than on developing and testing it;
• Withholding negative information from doctors or using questionable incentives to encourage the writing of prescriptions for a specific drug;
• Indirectly engineering a campaign to stimulate (while not actually promoting) one or more “off-label” uses of a drug that may actually generate more income for that drug than the approved uses. (The “off-label” market will be described below.)
These revenue-driven strategies do not make a drug better or safer. In fact, every case is little more than marketing winning out over science, safety, and even ethical considerations. In the case of Natrecor nothing good can be said concerning the manner in which the drug was promoted and marketed.
Natrecor, or nesiritide, was approved by the FDA in 2001 to treat congestive heart failure or acute decompensating heart failure in which patients experience shortness of breath and the heart fails to adequately pump blood to other organs in the body. The drug works by mimicking a hormone-like molecule that dilates vessels to prevent blood from gathering in the heart and lungs thereby allowing the patient to breathe.
Natrecor is manufactured by Scios, a company which was bought by Johnson & Johnson in 2003. As many as 600,000 patients have been treated with the drug since its approval.
Natrecor was, and still is, supposed to be used for the sole purpose of treating hospitalized patients with the aforementioned heart conditions. Despite this express limitation on its approved use; Natrecor has become an increasingly popular option in outpatient clinics nationwide where it is used for far longer periods than it was originally approved for.
Some outpatient clinics even administer Natrecor twice weekly for up to 12 weeks. This type of use is considered to be extremely dangerous as no study has been conducted to confirm whether long-term use is either safe or effective.
This “off-label” use of Natrecor has lead to the discovery of severe side-effects and a subsequent push from medical experts and consumer advocates for the manufacturer to conduct further large-scale, longitudinal studies of the drug.
The off-label prescribing of drugs beyond the scope of their approval by the FDA has become a serious concern in recent years. Dosage levels, medical conditions, and treatment durations for which drugs were never intended or tested make the entire area of off-label use problematic at best. At its worst, the practice can be downright deadly.
It is for this reason that the FDA regularly discourages and even warns against such uses of drugs. This has been especially true in the case of powerful drugs like antipsychotics, heart medications, and antidepressants.
The incredibly strange thing about off-label use, however, is that doctors may prescribe drugs to treat conditions for which the FDA has even denied approval. Thus, while a manufacturer cannot market a drug for an unapproved off-label use, a doctor may prescribe the drug for that use.
Thus, if a pharmaceutical company is able to subtly (or, even not so subtly) stimulate off-label use of one of its drugs, the return in unanticipated profits can be quite significant. In fact, a clever marketing scheme can turn a restricted approval drug with limited sales potential into a billion-dollar blockbuster.
Many times, off-label use of a drug is stimulated by doctors themselves who are acting more like marketing agents than as responsible health professionals.
Dr. Jonathan Sackner-Bernstein, a cardiologist at North Shore University Hospital in New York and an avid opponent of the overuse of Natrecor, co-wrote several journal articles that provide data which links Natrecor to kidney problems and elevated death rates.
Sackner-Bernstein’s patients taking Natrecor were 80% more likely to die within the next 30 days than patients who had received other treatments such as diuretics or vasodilators.
The issues relating to kidney safety were known prior to and during the process of FDA approval of the drug and are specifically noted in the drug’s labeling. Yet the increased risk of mortality was not entirely known or appreciated until the drug became widely used in outpatient clinics for extended periods of time.
Although Scios argued that the Sackner-Bernstein paper included studies done at higher doses than are advised on the drug’s label, those higher doses are precisely what patients are being exposed to when they receive the treatment outside of hospitals.
Natrecor was never approved to be used as frequently as it is being used in outpatient clinics. Sackner-Bernstien and other experts, including fellow cardiologist Keith Aaronson, have attempted to show that Natrecor should not be administered in outpatient settings and that the drug’s label should indicate the serious problems associated with unrestricted off-label usage.
In the July 14 edition of the New England Journal of Medicine, Dr. Eric Topol of the Cleveland Clinic was highly critical of the way in which Scios was marketing Natrecor and he even went so far as to state that the drug should be off the market because the FDA was never given sufficient data upon which to have based its approval.
Natrecor has been aggressively marketed with sales of the drug now reaching almost $700 million this year. This is because Natrecor is an expensive option, costing nearly 50 times more than standard therapy options.
Natrecor is billed to insurance companies at up to $700 per session. When used in hospitals for emergency situations, as intended, the cost, while high, is controllable. However, when patients are receiving this treatment dozens of times in outpatient clinics, the cost quickly spirals out of control.
In addition to other questionable marketing strategies, Scios provided doctors with promotional materials advising them on how to bill Medicare for Natrecor uses that are clearly not approved by the FDA.
The Scios reimbursement guide, also available through a toll-free number, told doctors to use Medicare codes that treat Natrecor like chemotherapy allowing them to bill for lager Medicare reimbursements.
As a result, Medicare managers became concerned that reimbursements for Natrecor treatments in outpatient clinics would skyrocket as a result of the information that Scios has been giving to medical professionals.
In May 2005, Johnson & Johnson announced that in compliance with the FDA, it would revise the labeling for Natrecor to include data indicating an increased risk of mortality within 30 days for Natrecor patients compared with patients taking a placebo or other treatments.
This was a good start but doctors and other medical professionals were still advocating further studies of Natrecor to determine the health risks associated with the drug. Milton Packer, a cardiologist at the University of Texas, Southwestern, is concerned that Scios, like Vioxx maker Merck, has not done adequate studies to make sure that its drug is safe. Although the FDA approved the drug in 2001, many doctors argue that today the vote might be closer and Natrecor would probably wind up with a tougher label.
Then, in May of this year, an independent expert panel, convened by Johnson & Johnson itself, recommended that Natrecor be restricted to severely ill hospitalized patients. Most experts also agreed that a large-scale clinical trial is needed in order to determine the risks of Natrecor.
Although a spokesperson for Scios argued that the company could not control how doctors prescribe the drug, Scios itself greatly contributed (or even created) the problem by affirmatively providing doctors with information on how to maximize their billing of Natrecor for off-label uses.
Many experts consider it ethically irresponsible for a pharmaceutical company to promote an off-label (and potentially harmful) use of a medication for no other apparent reason than financial gain.
Such questionable conduct could have caused significant problems for Scios and Johnson & Johnson if the drug does prove to be as dangerous as it appears to be and it continued to be prescribed in outpatient settings as opposed to hospital situations where it is a life-or-death situation.
In June, the panel of cardiologists convened by Johnson & Johnson and headed by the highly respected heart researcher, Harvard’s Dr. Eugene Braunwald, recommended strict limitations on Natrecor, including not using it for scheduled “tune-ups” or even administering it outside the hospital.
The panel specifically recommended that Natrecor only be used in cases of an acute type of heart failure when the patient actually shows up at the hospital; that it should not be used in place of diuretics, the first-line treatment for heart failure; and never used for outpatients, scheduled appointments, or to improve kidney function.
Furthermore, the panel believed that: “Scios should immediately undertake a proactive educational program to inform physicians regarding the conditions and circumstances in which [Natrecor] should and should not be used.”
A member of the panel, Barry Massie (professor of medicine at University of California in San Francisco) also expressed disapproval of the manner in which doctors flagrantly engage in the off-label prescribing of drugs. He believes it is important for doctors to take responsibility for their actions and only prescribe drugs for their approved uses. “It shouldn’t all be blamed on the pharmaceutical companies, no matter what they do to encourage unproven indications.”
On July 20, Johnson & Johnson acknowledged it had received a subpoena from the United States Attorney’s office in Boston requesting documents related to the sales and marketing of Natrecor.
As a result of this virtual tidal wave of disapproval concerning the questionable tactics associated with the marketing of Natrecor, Johnson & Johnson added a clear disclaimer to its hotline used by doctors seeking information on how to charge Medicare and insurance carriers for the drug. The disclaimer clearly seeks to discourage the heretofore rampant off-label use of Natrecor.
The disclaimer warns of the “lack of clinical data” regarding off-label use of the drug and that Scios “does not recommend Natrecor for this use.” Johnson & Johnson now plans to follow up on the panel’s suggestions.
Fortunately, in the case of Natrecor, the often ineffective checks and balances in the healthcare system finally worked to forever deprive Natrecor of the blockbuster status its manufacturers had so desperately attempted to achieve.