Shares of Nabi Biopharmaceuticals plunged 71.8 percent after the company halted further development of StaphVAX pending a deeper data analysis, as the product missed its primary endpoint in a Phase III trial to treat Staphylococcus aureus-caused infections in patients with end-stage renal disease.

Though it had been designed to confirm the statistical significance seen in a previous Phase III study, the study failed to show that StaphVAX reduced the incidents of S. aureus types 5 and 8 infections compared to placebo. The trial enrolled 3,600 patients on hemodialysis who were randomized to receive either StaphVAX, a polysaccharide conjugate vaccine or placebo.

"Unfortunately, we didn't find any significant reduction in the risk of developing Staph aureus infections in the patients," said Henrik Rasmussen, senior vice president of clinical, medical and regulatory affairs at Nabi.

Wall Street was disappointed. Nabi's stock (NASDAQ:NABI) fell $9.22 Tuesday to close at $3.63. The company's shares were downgraded by New York-based Bear, Stearns & Co. Inc. from "outperform" to "peer perform," and from "buy" to "sell" by Stanford Group Co., of Houston.

Nabi's focus now is analyzing the data and determining whether the company can move forward with the StaphVAX program, said Tom McClain, chairman, president and CEO of the Rockville, Md.-based company.

The question is why the results "ran contradictory to a previous Phase III clinical study in the same population, where we had demonstrated about a 60 percent reduction in infection in patients dosed with StaphVAX through 10 months," McClain said, referring to the trial completed in September 2000 involving 1,804 subjects.

In that trial, patients receiving Nabi's vaccine showed a 57 percent reduction in infection vs. placebo. However, the trial missed its overall endpoint of showing a statistically significant reduction through 12 months of treatment, the time period designated for evaluating the study's primary endpoint. After meeting with the FDA, the company agreed to conduct another pivotal study, that one testing StaphVAX's effect through eight months of vaccination. (See BioWorld Today, Sept. 20, 2000; Feb. 15, 2001; and Sept. 30, 2003.)

"So, basically, we had one study that was positive, and now one that is not showing a positive result," McClain said, adding that the company will begin working "to assess what may have happened between the two studies."

Nabi will compare isolates of the antibodies formed in response to the vaccine during both trials, as well as isolates of the bacteria, to determine any differences that could explain the disparate results.

"Over the next few days, we'll be designing experiments to look at the quality of the antibody, to see whether it has the same affinity to the bacteria in both trials," said Raafat Fahim, senior vice president of research, technical and production operations. "We'll also look at the bacteria to see how it may have changed over the past five years."

The analysis is expected to take the few months. At the same time, the company has invited an outside panel of experts to review the data. Results from both efforts will determine whether the company will proceed with its development activities.

In the meantime, Nabi has withdrawn its marketing authorization application for European approval of StaphVAX, and also stopped development of Altastaph (Staphylococcus aureus immune globulin intravenous) for the prevention and treatment of S. aureus infections. That product is based on the same capsular polysaccharide technology as StaphVAX.

One bit of good news from the Phase III trial is that it showed the vaccine's ability to elicit an immune response, indicating that the company's underlying technology is effective in producing and sustaining high levels of antibodies, McClain said.

"Immunogenicity is very important to us," he told BioWorld Today. "It proves that the vaccine technology, the carrier protein we use, is very strong and very robust."

Nabi's conjugate vaccine technology produced its smoking cessation product, NicVAX (nicotine conjugate vaccine), which is in a Phase IIb trial, and also served as the foundation for other vaccine programs in the bacterial infections area, though those vaccines do not rely on the capsular polysaccharide technology.

"We have some different technologies for Staph aureus in both hospital- and community-acquired infections," McClain said, including a vaccine against type 336 that is in Phase I development. He said the company also has a S. epidermidis vaccine in Phase I trials, and is in preclinical development with a vaccine against Enterococcal infections.

In addition, Nabi plans to advance its hepatitis C product, Civacir, a human polyclonal antibody product developed to treat patients following liver transplants. The National Institutes of Health has funded a Phase I/II trial of Civacir in hepatitis C-positive liver transplant patients to evaluate the product's safety and ability to produce antibodies.

The company reported a net loss of $16.1 million for the third quarter. Research and developments expenses totaled about $17.4 million for the three-month period, much of which was used to fund clinical and regulatory costs associated with StaphVAX. As of Sept. 30, Nabi had cash and marketable securities of $136.5 million.