Natrecor Use Should Be Limited, Independent Panel Convened By J&J Says

The cardiologist panel calls for use of the congestive heart failure therapy to be "strictly limited" to patients that present with symptoms in the hospital setting. The expert panel also recommends that Scios "immediately undertake" a professional educational campaign about Natrecor's appropriate uses.

Johnson & Johnson's Natrecor (nesiritide) should only be used in patients that present with symptoms in the hospital setting, according to an independent panel of cardiologists convened by the company.

Natrecor use "should be strictly limited to patients presenting to the hospital with acutely decompensated congestive heart failure who have dyspnea at rest," the panel report states.

That population would more closely resemble the patient population studied in the largest clinical trial that supported Natrecor's approval, the report states.

The panel's recommendation that Natrecor use be limited to the hospital setting is slightly narrower than the indicated use in labeling for the congestive heart failure therapy.

"Natrecor 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," nesiritide labeling states.

J&J's Scios subsidiary convened the panel, chaired by Eugene Braunwald (Harvard Medical School), to review and discuss nesiritide's risk/benefit profile, to provide guidance on proposed clinical development strategies, to review the current package insert and to provide recommendations on its use, the company said.

At its June 8 meeting in Boston, the panel heard presentations from Scios scientific staff and held two closed-door executive sessions to develop its recommendations, Scios said. The closed-door sessions were not open to the company.

The panel's meeting followed the publication of a meta-analysis in the Journal of the American Medical Association that reported an 80% increase in the risk of mortality after 30 days of Natrecor treatment compared to other therapies (¹ (Also see "Natrecor Safety Labeling Change Likely, J&J Says" - Pink Sheet, 19 Apr, 2005.)).

Natrecor's labeling was updated to include a revised analysis of mortality rates seen in nesiritide clinical trials, but did not add warnings about increased risk of death (² (Also see "J&J/Scios Natrecor Labeling Change Includes Expanded Mortality Analysis" - Pink Sheet, 21 Apr, 2005.)).

Updated Natrecor labeling also includes a precaution about the association with a higher risk of kidney dysfunction.

The panel's report outlines five ways in which Natrecor should not be used: as a replacement for diuretics, for intermittent outpatient infusion, for scheduled repetitive use, to improve renal function, or to enhance diuresis.

Natrecor labeling contraindicates use of the drug as primary therapy for patients with cardiogenic shock or in patients with a systolic blood pressure of <90 mm Hg. Natrecor is also contraindicated in patients who are hypersensitive to any of its components.

The cardiologist panel recommended that physicians consider "the availability of alternate therapies to relieve the symptoms of congestive heart failure" prior to prescribing Natrecor.

The panel also called for Scios to "immediately undertake a proactive educational program to inform physicians regarding the conditions and circumstances in which nesiritide should and should not be used."

Finally, the panel endorsed Scios' plan to conduct a large outcomes study to assess Natrecor's risk/benefit profile compared to other therapies.

J&J expects the results of its ADHERE registry, which are slated for publication in the Journal of the American College of Cardiology, to confirm Natrecor's safety (³ (Also see "Natrecor Safety Confirmed In ADHERE Heart Failure Registry, J&J Says" - Pink Sheet, 27 May, 2005.)).

- Steele Thomas