The anti-staph field got potentially more complicated last week when a would-be challenge to research leader Inhibitex Inc. appeared on the horizon.
MedImmune Inc. and pharmaceutical giant GlaxoSmithKline plc entered a licensing deal with unspecified money terms for anti-staphylococcal monoclonal antibodies (MAbs), including BSYX-A110, a monoclonal antibody targeting lipoteichoic acid in staph bacteria cells, which is in Phase II trials for preventing serious bloodstream infections caused by the Staphylococcus bug in low-birth-weight infants.
GSK, which licensed BSYX-A110 and related rights from Biosynexus Inc. in 2002, is paying undisclosed cash up front plus milestone payments and royalties on any products that come out of the arrangement. Phase IIa data are being sifted now, and a Phase IIb trial to test BSYX-A110's safety and efficacy is slated for next year.
Inhibitex has Veronate, nearing the finish line of Phase III trials against S. aureus. The company went public in June 2004, pulling down gross proceeds of just under $39 million, and Inhibitex raised about $41.3 million last month in a private placement. (See BioWorld Financial Watch, July 12, 2004.)
Money from the financing, Inhibitex said, would go for Veronate and the firm's second product, Aurexis, which had just completed a Phase II trial in 60 patients with life-threatening S. aureus bloodstream infections. Hospitalized patients were treated with Aurexis in combination with antibiotics, and Inhibitex is putting together a larger, follow-on, Phase II or Phase III trial that should begin around the end of this year.
Aurexis also is being studied in a 30-patient Phase II trial to evaluate its impact on S. aureus bacterial load and pulmonary inflammation in cystic fibrosis patients.
For Veronate, the market size isn't exactly clear. Figures date from the U.S. Census Bureau's findings from 2001, when about 43,000 infants weighing less than 1,250 grams at birth were born.
Veronate targets MSCRAMM proteins on the surface of pathogenic organisms that allow infection to start and keep going (Aurexis targets the same proteins), and Inhibitex could file a biologics license application in the second half of next year. Clinical lag aside, BSYX-A110 - by taking aim at lipoteichoic acid - could have trouble competing, since skeptics note the acid (unlike MSCRAMM) is sometimes released from the staph germs, and thus could draw some of the antibody's efficacy away from the live bacteria where it belongs. What's more, different strains of staph might release the acid at varying rates.
An abstract related to a Phase I/II study with BSYX-A110, reported last spring at the Pediatric Academic Societies meeting, was somewhat sketchy but said morbidities and mortality "were not different across study groups" (which could provide a clue as to why GSK gave it up after getting the compound from Biosynexus), whereas Veronate has proved strong in a Phase II study.
Another player is Nabi Biopharmaceuticals Inc., which has Altastaph (S. aureus immune globulin) in Phase II for the prevention and treatment of S. aureus infections.
The product deploys high levels of antibodies to capsular polysaccharides, the protective outer sugar coatings on S. aureus bacteria, from S. aureus types 5 and 8, which together account for about 85 percent of all S. aureus infections.
At the start of last year, the FDA granted orphan drug status to Altastaph for immediate protection against S. aureus infections in low-birth-weight neonates, and in February 2004 designated the compound as fast track. Nabi plans a Phase II trial next year with an improved version of its own drug, which will protect babies against S. epidermidis, as well as S. aureus.
"Coagulase negative [targeted by BSYX-A110] covers a wide range of staph," Henrik Rasmussen, senior vice president of clinical, medical and regulatory affairs for Nabi, told BioWorld Financial Watch, noting that the very prevalent coagulase-negative microorganisms and S. epidermidis germs are "almost synonymous, though not completely."
In May, Nabi began the first human study of its vaccine to prevent S. epidermidis in at-risk patients, which include neonates, as well as patients with in-dwelling catheters and patients undergoing certain types of surgery. The Phase I trial will evaluate the safety and immune response of the vaccine in up to 48 patients at four dosage levels, with results expected in the second half of the year.
Interestingly, Nabi's expertise against S. aureus drew a licensing deal in 2003 with Pharmacia & Upjohn Co. (now Pfizer Inc.), focused on Nabi's whole-cell vaccine technology for fighting the infection - in cattle. In March of this year, though, Pfizer "notified us that they would not pursue further development of a product" in that area, according to Nabi's annual report. "Pursuant to the license agreement, we retain our full rights to information and data generated under the agreement and have no further obligations to Pfizer."
Humans, of course, are another matter. Inhibitex's Veronate lacks activity against S. epidermidis, Rasmussen said, and the strength of Nabi's product in that regard could eventually distinguish it in the marketplace.
Meanwhile, though, the battle (if there is to be one, longer term) is shaping up between Veronate and BSYX-A110. For the treatment of S. aureus in very low-birth-weight infants, Veronate has orphan drug status and could get priority review. BSYX-A110, on the other hand, might be a few years away from a filing and, to win the FDA's favor, GSK/MedImmune might - depending on the outcome of Veronate's 2,000-patient Phase III study, which currently is enrolling - have to conduct a trial comparing the compound directly to the Inhibitex drug.