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XOMA is developing Neuprex, an injectable recombinant protein fragment (rBPI-21) of the naturally-occurring bactericidal/permeability increasing (BPI) protein, for serious infections and infectious complications of trauma and surgery. Neuprex is the most advanced compound from XOMA's BPI platform. Neuprex is planning to commence a clinical trial for at least one additional indication in 1998 [293193]. Meningococcemia The lead indication for Neuprex is meningococcemia, for which phase III trials are expected to be completed in the second half of 1998 [275644]. In June 1998, Neuprex received Orphan Drug designation from the FDA for the treatment of severe meningococcal disease. XOMA is preparing components of a BLA to be submitted to the FDA as soon as the ongoing phase III trial is complete [290059]. In an open-label pilot study in 26 patients, completed in 1996, the mortality rate was 3.8% (one death) compared with 22% (12 deaths in 55 patients) of patients treated at the same medical centers from the previous two years [264164]. A 200-patient phase III trial, testing Neuprex in children with severe meningococcemia, is being carried out in the UK and North America. An independent Data Safety Monitoring Board recommended continuation of the trial following an interim analysis of the data [264164]. Post hepatectomy A phase II trial in partial hepatectomy patients has stopped enrollment at 35 patients (due to the slow rate; XOMA intends to make progress in other hepatic studies). Data from the first interim safety analysis, on twelve patients (low-dose group), suggested that patients receiving Neuprex spent less time on respirator, in the ICU and in the hospital [282257]. Antibiotic-resistant infections In vitro studies have shown that rBPI-21 can make resistant bacteria more antibiotic-susceptible and enhance the potency of a broad range of traditional antibiotics. Hence, XOMA has commenced studies to examine Neuprex in situations where infections may be resistant to antibiotics. A 21-patient open-label trial of Neuprex as an adjuvant to antibiotics in the treatment of severe intra-abdominal infections has been completed. The results showed a consistent, dose-related improvement in patient outcome as measured by time to improvement and time to fever-free status, but few resistant bacterial strains were found in this study and none that were resistant to all three antibiotics used in the study [282257]. In November 1997, XOMA began a clinical trial evaluating Neuprex as an adjunctive therapy with conventional antibiotics in bacterial lung infections in cystic fibrosis (CF) patients. A second study site was added in January 1998. The pilot study will enroll up to 24 CF patients hospitalized for acute bacterial exacerbations [264398]. Post-hemorrhagic trauma The company is initiating a phase III clinical trial to evaluate Neuprex as a treatment to prevent infections and infectious complications in patients suffering from hemorrhagic trauma [268444]. A 401-patient, phase II hemorrhagic trauma trial showed a positive overall benefit in patients receiving Neuprex versus placebo [282257]. A follow-on study in 169 patients confirmed the original dosing regimen [282257]. Bactericidal/permeability increasing protein platform BPI is a human host-defense protein discovered in 1978 by Drs Peter ElsbachGerrold Weiss, at New York University (NYU) Medical School. BPI occurs in neutrophils. XOMA scientists have discovered three active areas (functional domains) within the N-terminal fragment of human BPI (the amino-terminal 199 amino acid fragment). Many peptides, derived from these domains, have been identified and characterized. Five classes of bioactivity have been shown: antifungal, antibacterial, endotoxin-neutralizing, heparinneutralizing and anti-angiogenic [282257]. XOMA has succeeded in producing recombinant versions of BPI proteins but has also modified them to fine-tune their function and improve their pharmacodynamic profile [162407,183566, 184024]. XOMA is New York University's exclusive licensee for patents relating to human therapeutic and diagnostic uses of rBPI. XOMA has also built a broad patent position related to its own work with BPI [282257]. In addition, in July 1998, XOMA licensed all of Incyte's BPI-related intellectual property, adding seven patents to XOMA's portfolio, which now includes worldwide rights to all existing BPI patents [293193]. |
