By Debbie Strickland
Five months after its lead product failed at Phase III, Scios Inc.'s Natrecor BNP for the short-term treatment of acute congestive heart failure (CHF) passed the pivotal trial by fire.
Upon release of the preliminary data, analysts David Stone and Felicia Reed of Cowen & Co., in Boston, upgraded the company's shares to "buy," calling the results "the turning point in the [Scios] story." They projected sales of $37 million by 2000, if the drug is approved and launched in 1999.
However, some Natrecor marketing issues remain, including competition from existing drugs that are apparently less effective but much cheaper. But if final analysis of Phase III results "show[s] a longer-term impact on symptom relief and a better side-effect profile, it could carve out a significant slice of the market," according to the analysts.
The company is keeping its U.S. marketing options open on this unpartnered product, though Scios will definitely seek a European marketing partner, Richard Casey, chairman and CEO, told BioWorld Today. Scios already markets seven psychiatric drugs, an operation that has generated cash to fund product development.
The Phase III news boosted Scios' shares (NASDAQ:
SCIO) Thursday to $8.934, a gain of 23 percent. The shares fell 30 percent to $4.687 in April following news that Auriculin, a treatment for oliguric acute renal failure, did not achieve its primary endpoint, dialysis-free survival.
First cloned by Scios researchers in 1989, Natrecor's active ingredient, human b-type natriuretic peptide (BNP), is a naturally occurring hormone produced predominantly in the ventricles of the heart. The body secretes BNP to combat fluid-overload states such as CHF, suggesting that BNP may be a natural regulatory response to a failing heart.
Auriculin, the company's former lead product, was based on atrial natriuretic peptide, or ANP. Both BNP and ANP are produced in the heart, and appear to produce similar biological effects, including elimination of salt and water from the body, dilation of blood vessels, and reduced secretion of other hormones which lead to blood vessel constriction and elevated blood pressure.
BNP, however, seems "clearly superior," said Casey, "either because it is more potent or because it circulates longer in the blood and hits more receptors."
NDA To Follow Next Year
Data from the Phase III efficacy study of Natrecor, along with results from a 300-patient safety study that has recently completed enrollment, will become part of the Phase III package in the company's first-ever new drug application (NDA), slated for submission to the FDA in the first half of 1998.
"Getting your first NDA is the major milestone for a biotech company," said Casey. "Having been in business almost 15 years, it's been a long road, and this is very important."
The randomized, double-blind, placebo-controlled efficacy trial enrolled 127 patients with acutely decompensated CHF requiring hospitalization. Patients received an infusion of either Natrecor (in one of two doses) or placebo. The primary endpoint of the trial was a reduction in pulmonary capillary wedge pressure (PCWP). Secondary endpoints included cardiac index and symptom improvement.
With respect to the primary endpoint, a preliminary analysis indicates Natrecor, compared with placebo, reduced PCWP by 20 percent at the lower dose level (0.015 mcg/kg/min) and by 30 percent at the higher dosage (0.03 mcg/kg/min). The safety trial will determine which dose is selected for the drug's label.
The drug also significantly improved symptom score and cardiac index vs. placebo. Additional data are under analysis.
According to the National Center of Health Statistics, acute CHF ranks among the leading causes of hospital admissions in the U.S., resulting in more than 1 million hospitalizations annually. About 10 percent of acute CHF patients die as a result of the condition.
"When patients are admitted to the hospital with acutely decompensated CHF, the goal of acute therapy is to rapidly improve the patients' cardiac function and relieve their symptoms, such as severe shortness of breath," said Wilson Colucci, the study chairman and chief of cardiology and director of the cardiomyopathy program at Boston Medical Center. "These Phase III results show that Natrecor is efficacious on both of these fronts." *