Staphylococcus aureus vaccine conjugate--Nabi: Nabi-StaphVAX, StaphVAX

Staphylococcus aureus is a major cause of hospital-acquired infections and infections in kidney dialysis patients. Over 90% of these infections are due to types 5 and 8. Nabi, under a CRADA agreement with the US National Institutes of Health, is developing a bivalent vaccine against S. aureus types 5 and 8 [Nabi-StaphVAX, StaphVAX]. The vaccine contains type 5 and type 8 S. aureus capsular polysaccharides conjugated to a protein carrier (recombinant exoprotein A, a genetically detoxified form of Pseudomonas aeruginosa exotoxin A). Nabi changed its name to Nabi Biopharmaceuticals on 5 March 2002. StaphVAX is available for licensing (http://www.nabi.com). Nabi's preference is for a licensee that can provide non-US marketing and regulatory capabilities in addition to financial resources to accelerate the vaccine's development. Nabi intends to develop a second-generation version of StaphVAX that will include antigen from Staphylococcus type 336. This would increase the vaccine's coverage of staphylococcal infection. Nabi also intends to develop two combination vaccines. The first, StaphVAX+ will contain both StaphVAX and EpiVAX trade mark in a single vial and the second, CombiVAX, will contain components of StaphVAX, EpiVAX trade mark and EnteroVAX trade mark. The vaccine has completed phase II clinical trials in chronic, ambulatory, peritoneal dialysis patients. Nabi-StaphVAX completed a multicentre, phase III trial in the US involving 1800 end-stage renal disease patients on haemodialysis. In September 2000, Nabi announced preliminary results from the phase III trial; these indicated that although Nabi-StaphVAX elicited a significant decrease in S. aureus bacteraemias in the first 10 months after vaccination, statistical significance was not reached in the primary endpoint of the study, a decrease after 1-year follow up. As a result, the US FDA indicated that US registration would require a second phase III trial in which the primary endpoint is reached. Following discussions with the US FDA, Nabi stated that the initiation of a second phase III trial in collaboration with a corporate partner was likely. Nabi intends to request either an accelerated- or fast-track review by the FDA, on the basis that the vaccine prevents a fatal disease for which no other prophylactics are available. In the meantime, Nabi initiated a boosting study of Nabi-StaphVAX in July 2001. This trial is administering a second dose of Nabi-StaphVAX to 100 patients enrolled in the phase III trial. Nabi plans to begin the confirmatory phase III study of the vaccine, as requested by the US FDA, in 3000 end-stage kidney patients in Q4 2003. The primary endpoint will be a statistically significant reduction of S. aureus bacteraemia caused by type 5 and 8 S. aureus through 8 months post-vaccination, the peak efficacy point in the first phase III trial. This trial will include a booster vaccination at 8 months and vaccinees will be followed up for up to 6 months after the booster to evaluate the vaccine's ability to generate antibodies, efficacy and safety. Results from this study will be used to support eventual product registration, now planned for 2005. In July 2003, Nabi reported that proceeds totalling 32.9 million US dollars from the private placement of its common stock to selected investors will enable the planned confirmatory phase III trial to proceed. In June 2003, Nabi Biopharmaceuticals announced the start of a clinical trial (a bridging study) to evaluate the safety and immunogenicity of a newly manufactured lot of StaphVAX produced by the contract manufacturer, Dow Biopharmaceutical Contract Manufacturing, intended for use in a planned confirmatory phase III trial later in 2003. The study demonstrated that the new batch of vaccine generated antibody levels that were equivalent to the levels generated by the vaccine produced at Nabi's R&D pilot plant and used in previous phase III studies.