Status - marketed in the U.S. and internationally

Organizations involved:

Scios Inc. – Manuf.; R&D; Tech.; USA mark.

California Biotechnology Inc. – R&D; Tech; Former

Johnson & Johnson – Parent

Quintiles Transnational Corp. – USA mark.

GlaxoSmithKline plc – Europe mark.; Former

Bayer Corp. – Former

Description: Natrecor is a lyophilized (freeze-dried) formulation of nesiritide, a recombinant B-type naturiuretic peptide (BNP) expressed in Escherichia coli (E. coli). Nesiritide is a peptide with the same 32 amino acid sequence as the endogenous human nesiritide peptide (BNP). A disulfide bridge, as in the natural human form, connects cysteine residues at positions 10 and 26, forming a ring of 17 amino acids with an amino-terminal extension of 9 amino acids and an carboxyl-terminal extension of 6 amino acids . Nesiritide has a molecular weight of 3,464 Dalton (3.46 kDa), and molecular formula of C143-H244-N50-O42-S4. Human nesiritide (hBNP) is a hormone secreted by ventricular myocardium of the heart in response to heart failure, regulating blood pressure by controlling fluid volume and blood vessel diameter.

Natrecor is formulated as the citrate salt of nesiritide packaged in single-use vials containing 1.58 mg nesiritide powder for intravenous infusion administration after reconstitution. Each vial also contains mannitol 20.0 mg, citric acid monohydrate 2.1 mg, and sodium citrate dihydrate 2.94 mg. Reconstitution involves adding 5 mL of diluent removed from a pre-filled diluent-containing 250 mL plastic IV bag, e.g., containing 5% Dextrose Injection, to the contents of a 1.5 mg vial of Natrecor. The reconstituted (dissolved) contents of the vial are then added back into the 250 mL IV bag, providing a solution with a concentration of Natrecor of approximately 6 µg/mL.

Nomenclature: natriuretic peptide, rDNA [BIO]; Natrecor [TR]; nesiritide [FDA]; Noratak [TR Europe]; B-type natriuretic peptide, recombinant [SY]; BNP [SY]; natriuretic peptide, B-type [SY]; SC-70400 [SY]; NDC 65847-205-25 [NDC]

Biological.: Human b-type natriuretic peptide (hBNP) or nesiritide is one of several natriuretic peptide hormone subtypes primarily secreted by the cardiac ventricles after increased cardiac volume and pressure overload. The effects of hBNP (and also recombinant nesiritide/Natrecor) and atrial natriuretic peptide (ANP) are both mediated by thee guanylyl cyclase A or GC-A receptors. hBNP and rhBNP bind to these receptors on the surface of vascular smooth muscle and endothelial cells, triggering intracellular activation of the secondary messenger, cyclic guanosine 3’5’-monophosphate (cGMP), leading to smooth muscle relaxation and dilation of blood vessels. Some of BNP’s vasodilating effects may be due to its ability to inhibit production of endothelin-I, a vasoconstrictive peptide, by endothelial cells.

hBNP is produced primarily in the left ventricle of the heart and is released when the heart fails. By ridding the body of salt and water, dilating blood vessels, and decreasing other hormones that raise blood pressure, BNP (both human and recombinant) improves heart function. Levels of endogenous hBNP are elevated in fluid-overload disease states, such as congestive heart failure. Clinical studies indicate that BNP has a number of effects, including increasing the excretion of sodium (natriuresis), excretion of fluids (diuresis), and dilation of blood vessels (increasing blood flow). These properties are useful for improving congestive cardiac performance. Animal and human studies suggest that BNP decreases the secretion of neurohormones (renin, aldosterone and norepinephrine) which lead to vessel constriction, fluid retention, and elevated blood pressure.

BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to increased intracellular concentrations of cyclic guanosine 3’5’-monophosphate (cGMP) and smooth muscle cell relaxation. Cyclic GMP serves as a second messenger to dilate veins and arteries. Nesiritide has been shown to relax isolated human arterial and venous tissue preparations that were precontracted with either endothelin-1 or phenylephrine, an alpha-adrenergic agonist. In human studies, nesiritide produces dose-dependent reductions in pulmonary capillary wedge pressure (PCWP) and systemic arterial pressure in patients with heart failure. Naturally occurring atrial natriuretic peptide (ANP), a related peptide, increases vascular permeability in animals and humans, and may reduce intravascular volume.

Companies.: Natrecor was developed and is manufactured by California Biotechnology Inc., renamed Scios Corp.. Scios is now a subsidiary of Johnson & Johnson (J&J), which in Feb. 2003, announced its intension to acquire Scios (whose only marketed product is Natrecor) for $2.4 billion. Bayer AG originally held exclusive international marketing rights. In Jan. 2002, Scios licensed European marketing rights to GlaxoSmithKline plc.

Scios has formed a marketing alliance with Quintiles Transnational Corp. to commercialize Natrecor for the treatment of acute decompensated congestive heart failure (CHF) in the U.S. PharmaBio Development, Quintiles’ corporate ventures group, provided $35 million in funding for Natrecor commercialization. Quintiles’ Innovex pharmaceutical product commercialization unit was to deliver a wide range of sales and marketing solutions for Scios, including training and establishing a 180-person sales group. Innovex was to provide services through Dec. 31, 2004. With the acquisition of Scios by J&J, this marketing alliance has been terminated, with J&J assuming U.S. and international marketing.

In July 2005, with mounting concerns about safety and significantly depressed sales, J&J reacquired European marketing rigths from GlaxoSmithKline.

FDA class: Drug NDA

Approvals: Date = 20010810; NDA (no. 020920), first approval

Date = 20040704; NDA supplement; Indication = an as yet undisclosed labeling revision

Date = 20050500; NDA supplement; Indication = information was also added to Natrecor’s labeling, including noting an increased risk of death compared with other treatments.

Indications: [full text of the "INDICATIONS AND USAGE” section of product insert/labeling]:

Natrecor (nesiritide) is indicated for the intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity. In this population, the use of Natrecor reduced pulmonary capillary wedge pressure and improved dyspnea.

Status: The NDA was filed in April 1998, and approved on August 13, 2001 (approval time = ~3.4 years) with new chemical entitity (NCE) designation (providing 5 years of market exclusivity). Prior to approval, it took about 20 months for Scios to conduct a clinical study in response to issues raised in an FDA approvable letter. FDA was concerned that Natrecor reduced blood pressure too much in a small percentage of patients. Natrecor was the first new drug to treat congestive heart failure in 14 years.

The Cardiovascular and Renal Drugs Advisory Committee, FDA, had recommended approval of Natrecor in Jan. 1999. The FDA acknowledged that Natrecor reduced pulmonary capillary wedge pressure, increased cardiac output, and produced some evidence of symptomatic benefit. However, FDA did not follow the committee’s recommendations (relatively unusual), and issued an approvable letter requesting further data to define the consequences of Natrecor’s pharmacodynamic profile, specifically as it relates to the onset of effect and the recovery from hypotension, if it occurs. Bayer dropped out of its marketing agreement with Scios after this. Scios started another Phase III trial in Oct. 1999. In Jan. 2001, Scios filed an amendment to its 1998 NDA filing.

In Oct. 2004, a study in the Journal of Emergency Medicine reported six deaths (5 for Natrecor, 1 placebo) ongoing PROACTION double-blind, placebo-controlled Phase IV trial, but that the difference in all-cause mortality at 30 days after treatment with Natrecor or placebo was not statistically significant. In Jan. 2005, interim data from a 180-day expanded analysis of PROACTION showed 2 new patient deaths within 30 days of treatment. J&J began an investigation into why the two additional deaths were not reported, and if they change the published conclusions regarding the trial.

In March 2005, an article was published in Circulation suggesting that Natrecor is associated with an increased risk of kidney problems. In the April issue of the Journal of the American Medical Association (JAMA), the same researchers published a meta-analysis of three prio clinical trials involving a total of 862 patient showing that Natrecor use was associated with an 80% increase in the risk of mortality one month after treatment, compared to conventional therapies, such as vasodilators and diuretics. J&J called the study a “selective interpretation of existing published data,” rather than new research.

In May 2005, the 50 physicians of the department of cardiovascular medicine, Cleveland Clinic, one of the largest centers for cardiac care in the U.S., voted unanimously to severely curtail or even ban the clinic’s use of Natrecor. This foreshadowed rejection or further restrictions on use of Natrecor by other health care organizations, insurers, and regulatory actions (with the Cleveland Clinic similarly taking the lead in banning use of Bextra months before FDA acted against the drug).

In June 2005, responding to concerns about safety and cost-benefit, a panel of clinicians appointed by Scios/Johnson & Johnson recommended that use of Natrecor be “strictly limited” in hospitalized acutely decompensated congestive heart failure (CHF) patients who have dyspnea at rest, and that it only be administered in a hospital setting. The panel also recommended that Natrecor not be used to replace diuretics and that Scios/J&J should undertake a pro-active educational program to inform physicians about correct usage. In July 2005, Scios/J&J issued a “Dear Doctor” letter to 160,000 U.S. healthcare professionals about the panel’s recommendations. In Aug. 2005, Scios launched “a comprehensive recommended use initiative” for Natrecor. This included (re)training the entire sales force and all promotional speakers, new promotional materials, and an advertising in top-tier medical journals.

In July 2005, Scios/Johnson & Johnson received a subpoena from the U.S. Attorney’s Office in Boston requesting documents related to the alleged sales and marketing of Natrecor for off-label indications: (use in less severe CHF patients).

In Jan. 2006, Scios submitted an interim report to FDA and other regulatory authorities with its expanded analysis of the three-year-old PROACTION exploratory health outcomes study comparing treatment with Natrecor to placebo. This included two additional deaths that had occurred within 30 days after treatment that not been initially reported. Scios expressed confidence these two additional cases have no impact on the overall benefit/risk profile of Natrecor for its approved indications:.

Natrecor has not received centralized European Union approval. Scios/J&J appears not to have filed for EU approval.

In Feb. 2009, the U.S. government intervened (joined) in two whistleblower suits filed in the Northern District of California againstScios Inc. and its parent company, Johnson & Johnson Inc., alleging that the companies marketed the Natrecor off-lable and caused false and fraudulent claims to be submitted to federal health care programs. Allegedly, shortly after receiving approval in 2001, Scios began an aggressive campaign to market Natrecor for scheduled, serial outpatient infusions for patients with less severe heart failure -- a use not included in the FDA-approved label. These patients were prescribed Natrecor infusions for less than six hours on a scheduled basis over an extended period of time. Medicare does not cover pharmaceuticals for off-label uses unless established to be medically necessary. The federal health care programs -- in particular, Medicare -- paid substantial amounts for the serial outpatient off-label use of Natrecor.

In July 2011, after several years of investigating, the U.S. Dept. of Justice filed charges against Johnson & Johnson's Scios division over its marketing of Natrecor. Prosecutors levied a misdemeanor charge of mislabeling Natrecor, and J&J faces a $200,000 fine. The charges stemmed from a probe first prompted by the prior whistleblower lawsuit. Scios allegedly sponsored seminars on Natrecor's off-label use; and hired a consultant to create a guide to help doctors bill Medicare for off-label use. The Justice Department had joined the whistleblower suit, but the case was dismissed later in 2009.

In Oct. 2011, Scios/J&J pleaded guilty today misdemeanor violation of the Food, Drug and Cosmetic Act (FDCA) for introducing into interstate commerce Natrecor for a use that was not approved by FDA. The District Court sentenced Scios to pay an $85 million criminal fine in accordance with the plea agreement between Scios and the government. Scios admitted that it intended Natrecor to be used off-label for infusing chronic (non-acute) CHF patients on a scheduled, serial basis and that it understood that this was not an approved use. Scios also admitted that the FDA-approved labeling for Natrecor did not contain any directions for this scheduled, serial use to treat chronic (non-acute) patients.

Tech. transfer: In Jan. 2013, the Orange Book cites 5,114,923, "Recombinant techniques for production of novel natriuretic and vasodilator peptides," originally set to expire May 19, 2009, but extended 5 years to May 19, 2014. The FDA Orange Book had previously reported that U.S. 5,114,923, expiration May 19, 2009, provides protection for Natrecor; and that Natrecor has new chemical entity-based exclusivity through Aug. 10, 2006.

The product insert cites U.S. 5,674,710, assigned to Scios, Inc., and 5,114,923, assigned to California Biotechnology (now Scios). These patents describe recombinant human and other mammalian natriuretic peptides, including nesiritide. U.S. 5,047,397, assigned to California Biotech., describes synthetic linear analogs of atrial natriuretic peptide, including nesiritide, methods for production, and medical uses.

U.S. 6,974,861, "Pharmaceutical compositions and methods using natriuretic peptides," assigned to Scios/J&J, includes claims for sequences, induction of natriuresis, diuresis and/or vasodilation, and use for treatment of congestive heart failure, expired on May 31, 2008.

Abbott Labs., Shionogi & Co., and Biosite Diagnostics have taken options to license recombinant B-type naturiuretic peptide from Scios for chronic heart failure diagnostics.

Trials: Natrecor has been shown in clinical trials to improve hemodynamics and symptoms faster, more effectively, and with fewer side effects than intravenous nitroglycerine. The pivotal trial supporting approval, VMAC (Vasodilation in the Management of Acute Congestive heart failure), in nearly 500 patients compared Natrecor to nitroglycerin. Natrecor showed a statistically significant effect on the primary end point,reduction of pulmonary capillary wedge pressure, and improved breathing. The hemodynamic effects of Natrecor are sustained through 48 hours without dose increases. Treatment is generally well tolerated, even in the most severely ill patients.

In Sept. 2004, results were reported from the Mortality and Length of Hospital Stay in Patients Receiving Dobutamine, Milrinone, or Nesiritide for Acute Decompensated Heart Failure (HFSA #317) study, a retrospective cohort analysis of the University HealthSystem Consortium (UHC) Clinical Database from 32 academic health centers. The final cohort included 2,130 acutely decompensated heart failure patients (dobutamine n=1,311; milrinone n=433; nesiritide n=386). The mean length of stay (LOS) for patients receiving nesiritide (7.0 +/-5.3 days) was lower compared to those receiving dobutamine (10.4 +/-12.9 days; p=0.012) or milrinone (12.2+/- 29.9 days; p<0.001). In-hospital mortality rates for dobutamine, milrinone, and nesiritide were 10.2%, 7.9%, and 2.9%, respectively. The adjusted odds ratio for death with dobutamine and milrinone, as compared to nesiritide, were 3.5 and 4.1 (p<0.0001), respectively.

In a March 2005 article in Circulation, based on a review of 1,200 patients, investigators concluded that Natrecor caused a 40-50% greater risk of reduced kidney function when compared with more conventional therapies for heart patients. Reduced renal function was linked to a higher death rate for patients with congestive heart failure. The investigators concluded, “Until there’s a definitive study, Natrecor is a drug that should be used only when other drugs don’t work.” Johnson & Johnson responded that the analysis was flawed, with the doses studied being up to three times the recommended dose, and that risk of reduced kidney function was already in the product insert/labeling.

In the April 19, 2005 issue of the Journal of the American Medical Association, results were reported from a study indicating that Natrecor use in pateints with congestive heart failure increased risk of death by 80% in the first month after treatment, compared to other treatments. This was based on meta-analysis of combined results from three clinical trials. Among studies of nearly 900 heart failure patients, 7.2% of patients died within 30 days of treatment with Natrecor, compared with a 4% death rate among controls. A longer, larger study was recommended to determine the safety of Natrecor. Individually, none of the three trials’ data supported a conclusion of a significant increase in risk for death, and essentially all of this data had been reviewed as part of the approval process.

After these negative results, Scios assembled an expert panel to advise it on whether new studies of Natrecor’s safety would be needed; and as is usual in such cases, various lawsuits seeking damages were filed on behalf of patients having received Natrecor. The panel, which was appointed by Scios/J&J, recommended more trials after concluding that Natrecor is associated with increased risk of kidney problems and mortality. The panel also recommended narrowing the use of the drug to treat hospitalized patients and patients that present at the hospital with acutely decompensated congestive heart failure (CHF) who have dyspnea at rest.

In mid-2007, following recommendations of its expert panel, Scios/J&J initiated the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) global, multi-center outcomes trial of Natrecor in ~7,000 patients. The trial is evaluating improvements in dyspnea, global symptomatic improvement, 30- and 180-day mortality, renal function, quality of life, rehospitalization, and pharmacoeconomics. This is the largest trial ever in the acute heart failure field. It is being conducted to further assess clinical outcomes as well as the benefit and safety profile in patients with acutely decompensated heart failure (ADHF). The trial’s key efficacy objectives are to assess whether Natrecor, in addition to standard care, compared with placebo and standard care, provides significant improvement in symptom relief, heart failure rehospitalization, and mortality after admission to the hospital. Other important clinical endpoints include safety, renal function and health economics.

In Feb. 2007, results from the NAPA trial indicated Natrecor may be beneficial in the prevention of renal dysfunction after coronary artery bypass grafting requiring cardiopulmonary bypass. The randomized, prospective, multi-center, double-blind Phase II NAPA (Nesiritide Administered Peri-Anesthesia in Patients Undergoing Cardiac Surgery) trial in 279 patients was designed to determine the role Natrecor may play in the management of patients with left ventricular dysfunction undergoing coronary artery bypass grafting (CABG) requiring cardiopulmonary bypass. Patients in the study were experiencing heart failure and had limited treatment options. Those taking Natrecor had improved outcomes, including shorter hospital stays and a statistically significant decrease in mortality rate after 180 days, vs. patients receiving placebo. Patients on nesiritide had significantly greater urine output within 24 hours after surgery and overall better preservation of kidney functioning during hospitalization and two weeks after surgery.

In March 2007, it was reported that FUSION II (Follow-Up Serial InfusiOns of Natrecor in Advanced Heart Failure), an exploratory, 920-patient, Phase I study of Natrecor, showed a neutral effect on the primary endpoint, a composite of death and cardiorenal hospitalization at 12 weeks. The trial also provided important renal and mortality safety data in patients with advanced chronic decompensated heart failure (CDHF) receiving serial outpatient infusions. FUSION II was designed to assess the long-term safety and outcomes at six months of once- or twice-weekly infusions of nesiritide compared to placebo in persistently symptomatic CDHF patients. All patients received ongoing intensive heart failure disease management, including optimization of standard heart failure medications and once or twice weekly outpatient clinic visits. Patients had to have two prior recent hospitalizations, either NYHA class III or IV heart failure, and had to have been out of the hospital for at least five days prior to enrollment in the trial. The study demonstrated comparable renal and mortality effects in both study arms. There was no statistically significant difference in the primary endpoint between patients receiving nesiritide compared to patients receiving placebo infusions when each was added to optimal heart failure medications, significant use of indicated heart failure devices and intensive disease management (i.e., Natrecor failed to show efficacy vs. placebo). Safety outcomes, including overall mortality and renal hospitalization and mortality were not statistically significantly different between Natrecor and placebo recipients (i.e., it was shown safe). The companies put on a positive spin, i.e., that the safety findings from the FUSION II trial showing safety in severe, chronic heart failure and other recent clinical studies should be reassuring for physicians who use nesiritide to treat patients according to its currently labeled indications:. These findings may help in neutralizing the decrease in sales after the April 2005 JAMA article and other studies indicating safety problems. Mortality data from FUSION II have been incorporated in Natrecor’s labeling.

Medical: For use, the powder reconstituted in a 250 mL intravenous infusion bags is is administered a a bolus at 2 µg/kg followed by intravenous infusion at 0.1 mL/kg/hr. Using a table provided in the product insert, a 70 kg (154 lb.) patient would receive a 1 minute bolus of 23.3 mL followed by infusion at a rate of 7 mL/hour. Blood pressure should be monitored closely during Natrecor administration.

Natrecor (and human BNP) has beneficial effects on acute decompensated congestive heart failure (CHF) by a combination of hemodynamic (balanced vasodilation, preload and afterload reduction), neurohormonal (inhibition of renin-angiotensin-aldosterone and norepinephrine), and renal (diuresis and natriuresis) effects.

Disease: Congestive heart failure (CHF) is characterized by a progressive loss in the heart’s ability to pump blood. Fluid can back up and pool in the lungs causing shortness of breath and/or can accumulate in the ankles causing swelling. This is why heart failure is often called “congestive” heart failure, or CHF. The term “decompensated” is a medical term used to describe patients with these symptoms. Inotropic agents, such as Natrecor, are a class of drugs that stimulate the heart to contract more forcefully to pump out more blood. Intravenous inotropic agents are used to treat patients with severe heart failure marked by a dangerously low output of blood from the heart.

During an episode of acute decompensated congestive heart failure (ADCHF), the heart’s inability to adequately circulate blood throughout the body worsens beyond its already compromised state, causing symptoms to become so pronounced that hospital treatment is required to stabilize the patient’s condition. A sudden increase in dietary sodium (salt), failure to take chronic oral medications, or the development of a new heart event can precipitate ADCHF. Virtually all congestive heart failure (CHF) patients have at least one severe acute episode.

About five million Americans suffer from heart failure, with 550,000 new cases diagnosed each year. According to the American Heart Association Heart Disease and Stroke Statistics -- 2004 Update, congestive heart failure affects more than 5 million Americans, and the cost of treating congestive heart failure patients in the U.S. will be $28.8 billion in 2004. Other sources report approximately one million hospitalizations each year in the U.S. due to acute CHF, costing the healthcare system ~$15 billion annually; with another two million Americans are hospitalized each year with acute CHF as their secondary diagnosis. In the U.S., CHF accounts for the single largest cause of hospitalizations for patients over age 65. Natrecor is particularly used in CHF patients experiencing difficulty breathing.

Market: Natrecor sales were estimated to be about $400 million in 2005 before it encountered major problems, e.g., the NEJM study reported in Sept. The author’s rough/crude guess for 2006 sales is $50-$100 million, and about $450 million in 2005 (with a reported $400 million in sales before bad press from negative trial results). Sales were about $395 million in 2004, roughly about $150 million in 2003, $107.3 million in 2002, and $14.1 million in 2001 (launched in Aug.).

Sales have substantially decreased since early-mid 2005, when many began further questioning the safety of Natrecor. At the time of Natrecor’s problems reported in spring 2005, it was reported that Natrecor was on track to reach sales of $700 million/year. For example, in 2004, sales in 2005 had been expected to exceed $600 million.

The 2007 Average Wholesale Price (AWP) is $572.33/1.5 mg single daily vial (Red Book, 2007). Upon approval, Natrecor had a wholesale cost of $380/vial, while nitroglycerine costs only $10-$15 per daily dosage. The AWP was $529.93 in 2005, and $507.60 in 2004. Upon approval, Natrecor had a reported wholesale cost of $380/vial, while nitroglycerine then cost only $10-$15 per daily dosage.

About 130,000 infusions of Natrecor for CHF were estimated in 2004, out of the estimated 1,000,000 cases of CHF in the U.S. (indicating that 13% of CHF patients received Natrecor). In early 2005, it was reported that ~600,000 infusions of Natrecor in the U.S. have been performed since its launch.

In July 2005, it was reported that tens of thousands of patients in the U.S were receiving “tune-ups” with Natrecor on an outpatient basis, an indication for which the drug is not approved, with Natrecor “now being used 10 times more often in outpatient clinics than in acute hospital settings.” This followed the reporting of safety problems with Natrecor only a few months earlier. Scios is alleged to have encouraged physicians to start their own outpatient Natrecor “infusion centers,” which would be billed to Medicare, including setting up a toll-free “Natrecor Reimbursement Support” hotline and publishing a 46-page reimbursement and billing guide providing physicians with specific Medicare billing codes. Many viewed these actions as illegal marketing for off-label indications:, while Scios/J&J claims these actions are fully legal. The U.S. District Attorney in Boston has been investigating Scios’ marketing of Natrecor.

Scios (with assistance from Quintiles) originally fielded a sales force of 165 upon launch of Natrecor.

With only a small percentage of the millions of persons annually treated for congestive heart failure receiving Natrecor, there is considerable potential for growth in sales, particularly with Johnson & Johnson (J&J), a major international pharmaceutical company, having assumed marketing. However, with J&J having paid $2.4 billion to acquire Scios, whose only product is Natrecor, with annual sales of Natrecor now not even reaching $.5 billion, and with continuing doubts and negative reports about the product’s safety and off-label use and Natrecor’s improper marketing, sales will likely further reduce or stall. J&J’s acquisition of Scios is likely to not be profitable for J&J (to put it mildly).

In Dec. 2005, Center for Medicare and Medicaid Services (CMS) requested public comments concerning a proposal to deny reimbursement for in-office Natrecor use to treat chronic heart failure (CHF), an off-label indication. The proposed decision would not change coverage of Natrecor for acutely decompensated heart failure (the approved indication).

In Feb. 2006, Scios (a J&J subsidiary) restructured, including laying off 150 employees (leaving ~750), primarily in sales and marketing, inorder to “return the drug [nesiritide] to growth.”

Competition: CoGenesys Inc., spun-off from Human Genome Sciences Inc. is developing a long-acting B-type natriuretic peptide using HGSI’s albumin-fusion protein technology, which it expects will avoid the problems associated with Natrecor nesiritide.