Trial staph vaccine fades down the stretch
Shorter-term use may still be option
A vaccine under development for Staphylococcus aureus infections showed promise of efficacy in initial research, but it stumbled badly at the one-year endpoint that concluded the trial. Researchers still hold out hope that the development of a booster dose — or use in different patient groups for shorter periods — could salvage the utility of the vaccine, which could be a key weapon against the scourge of antibiotic-resistant staph infections.
Preliminary data from a double-blind, placebo-controlled phase III trial of StaphVAX were presented recently in Toronto at the Interscience Conference on Antimicrobial Agents and Chemotherapy. The vaccine is under development by National Institutes of Health and the Nabi Corp. of Boca Raton, FL. In the promising first 10 months of research, the vaccine showed a 57% reduction in bloodstream infections in 1,804 end-stage renal disease patients on hemodialysis. But the primary endpoint was one year, and StaphVAX failed to achieve statistical significance at that duration.
"It’s [still] a very positive outcome for this trial," said Gary Horwith, vice president of clinical research and medical affairs for Nabi. "What we need to address at this point [are] ways to boost the vaccine and make it more durable [in the patient population studied]. We planned to do that anyway in phase IV."
Jonathan Gal, analyst and president of Biocoverage Inc. in Cambridge, MA, said positive data even at 10 months for this indication constitute "a milestone in medical history. I think there’s still a good chance the FDA will give them a green light and let them file for a [biologics license application] because of the environment around the disease. It’s serious."
StaphVAX is made of capsular polysaccharides from the two most common serotypes of S. aureus, each conjugated to a carrier protein. Testing the vaccine in patients with fully competent immune systems would have been preferable, but finding such patients suitable for a full clinical trial was nearly impossible, Horwith said.
"We knew we had an uphill battle going into it, using this patient population," he said, noting that many of those for whom StaphVAX might be used, if approved, would be patients undergoing surgery who find themselves at high risk for a much shorter period. Evaluating StaphVAX’s efficacy for a shorter period and building in the likelihood of boosters were options, he added, but the 12-month endpoint is "kind of an arbitrary but convenient and conventional time frame. There’s nothing magic about it, and you know there’s going to be a drop in antibodies over a period of time. It was the luck of the draw we saw [efficacy] at 10 months and not at 12 months."
In other pharmaceutical news from ICAAC:
AnorMED Inc. of Vancouver, British Columbia, presented data on AMD-8664, an orally administered drug candidate with the potential to block HIV from entering and infecting healthy T-cells. AMD-8664 has exhibited inhibition of HIV infection and good oral absorption properties in preclinical studies.
Aronex Pharmaceuticals Inc. of The Woodlands, TX, presented clinical, preclinical, and pharmacokinetic data for Nyotran, its product for systemic fungal infections. Results were positive in a phase II clinical trial in refractory or intolerant patients with invasive Aspergillus, in a comparative urinary pharmacokinetics and drug disposition study, in efficacy trials in the treatment of disseminated candidiasis in guinea pigs, and in a differential in-vitro antifungal activity study. Aronex anticipates submission of a new drug application in 2001.
Cubist Pharmaceuticals Inc. of Cambridge, MA, reported positive safety and efficacy data on Cidecin (daptomycin for injection) in a completed phase I dose-escalation study. Also, data from Cubist’s two ongoing phase II studies showed daptomycin had an overall clinical success rate of 93% in the intent-to-treat population and 100% in the clinically evaluable patients. Cidecin is an antibiotic that has demonstrated rapid bactericidal activity against gram-positive bacteria, including strains resistant to current therapies.
Tibotec of Mechelen, Belgium, presented results on R165335-TMC125, one of its lead anti-HIV nonnucleoside reverse transcriptase inhibitors (NNRTI). NNRTIs are standard components of HIV combination therapy, but cross-resistant HIV strains have limited the effectiveness of current NNRTIs. R165335-TMC125 inhibited 98% of all clinical isolates tested and 97% of the NNRTI-resistant strains. n
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