Various data were reported during this week's Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago. Among findings from the conference, which began Sunday and runs through Wednesday, were the following reports:
• Abbott Laboratories, of Abbott Park, Ill., said the majority of patients initiating therapy with Kaletra (lopinavir/ritonavir) as part of their treatment regimen achieved and maintained undetectable HIV viral load - amount of virus in the blood less than 50 copies per milliliter - through five years of treatment. The data demonstrated that undetectable virus levels could be maintained when the protease inhibitor was dosed in combination with two nucleoside reverse transcriptase inhibitors. The low viral loads, as measured by HIV RNA, were accompanied by increases in CD4 cell counts, even for patients with the most advanced disease. Also, the data showed that Kaletra was generally well tolerated as part of an initial HIV treatment regimen.
• Agouron Pharmaceuticals Inc., a unit of Pfizer Inc., of New York, said that nelfinavir mesylate (Viracept) appears to have a favorable profile when taken by HCV/HIV co-infected patients. More specifically, the retrospective study revealed mean CD4 cell-count changes for patients with baseline CD4 cell counts less than 50, 50 to 200, and greater than 200 were, respectively +179, +153 and +83. In the nelfinavir group alone, CD4 increases were +178, +130 and +89, respectively. For the same baseline groups, mean viral load changes were -1.5 log10 (46 percent with less than 400 copies/mL), -1.2 log10 (57 percent with less than 400 copies/mL) and -0.9 log10 (61 percent with less than 400 copies/mL). For the nelfinavir patients, the following viral load decreases were noted: -1.7 log10 (46 percent with less than 400 copies/mL), -1.6 log10 (52 percent with less than 400 copies/mL) and -1.0 log10 (64 percent with less than 400 copies/mL). Also, nelfinavir showed fewer high-end elevations in aspartate aminotransferase and alanine aminotransferase in comparison to the other protease inhibitors - elevated serum levels of the two can be indicators of liver damage.
• Cel-Sci Corp., of Vienna, Va., said it presented data demonstrating that its CEL-1000 peptide initiates protection from lethal challenge with herpes simplex virus in animals, and shows how the protection is initiated. The data show that after CEL-1000 treatment, the cytokine interleukin-12 is released and found in the blood. It was further demonstrated that interferon gamma and CD4-expressing cells are important elements for initiating and expanding the response to CEL-1000 and for delivering the protection from herpes disease. The work was done in collaboration with a Cel-Sci scientist.
• Genome Therapeutics Corp., of Waltham, Mass., reported in vitro and in vivo activities of Ramoplanin against a variety of pathogens, including vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant enterococci (VRE) and Clostridium difficile. Findings showed that Ramoplanin had a low minimum inhibitory concentration of 0.12 ug/ml and, along with several other antibiotics tested, was rapidly bactericidal against VRSA. Other posters detailed Ramoplanin's in vitro activity against strains of C. difficile resistant to standard therapy (metronidazole), measured C. difficile's lack of resistance to Ramoplanin and determined that Ramoplanin produced superior efficacy compared to vancomycin in treating a hamster model of C. difficile-associated colitis. The product is in a Phase III trial to prevent bloodstream infections caused by VRE and a Phase II study to treat Clostridium difficile-associated diarrhea.
• Human Genome Sciences Inc., of Rockville, Md., reported in vitro and in vivo preclinical data showing that a single dose of ABthrax increases survival significantly in both rabbit and nonhuman primate models of inhalational anthrax. ABthrax (human monoclonal antibody to Bacillus anthracis protective antigen) is designed to prevent and treat anthrax infections. Last month, the FDA conferred fast-track status on the product, which Human Genome Sciences has moved into a Phase I placebo-controlled, dose-escalation trial to evaluate its safety, tolerability and pharmacokinetics in healthy adult volunteers.
• Peninsula Pharmaceuticals Inc., of Alameda, Calif., said data presented from studies of doripenem (also known as S-4661) in Western populations supplement safety and efficacy findings in numerous Japanese studies. The company added that the results better define the antimicrobial activity and pharmacokinetic/pharmacodynamic parameters of doripenem, allowing Peninsula to design and implement a Phase III program to direct the drug toward regulatory approval. The company recently reported the early completion of its Phase II study of the carbapenem compound.
• PhageTech Inc., of Montreal, said it identified small-molecule compounds that effectively kill or inhibit the growth of disease-causing bacteria after identifying phage-derived antimicrobial proteins and using them as tools to discover bacterial targets essential to bacterial growth. More specifically, its researchers used high-throughput phage genomics and functional genomics strategies to sequence the genomes of 43 phages that infect three human pathogens: Staphylococcus aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa. Subsequent screening against the targets yielded several small molecules that appear to mimic the phage-derived inhibitory proteins in their antimicrobial effects. PhageTech said its researchers continue to screen libraries of small-molecule compounds against the newly identified targets for drug-like compounds that effectively inhibit or kill bacteria in the same manner as the phage-derived inhibitory proteins.
• Trimeris Inc., of Durham, N.C., and F. Hoffmann-La Roche Ltd., of Basel, Switzerland, reported data showing that 80 percent of patients receiving a Fuzeon (enfuvirtide)-based anti-HIV drug regimen who achieved undetectable levels of the virus at 24 weeks maintained the response at 48 weeks. Researchers also reported that 37 percent of treatment-experienced patients treated with a Fuzeon-based combination maintained at least a 90 percent reduction in blood levels of HIV at 48 weeks, vs. 17 percent of patients on a regimen without Fuzeon. Separate data from a Phase I/II study of a second-generation fusion inhibitor, T-1249, showed that after 10 days of treatment, 73 percent of patients demonstrated a greater than 1.0 log10 reduction in HIV RNA. Safety evaluations revealed no serious adverse events relating to T-1249. The study included 53 patients who were participating in Phase II or Phase III studies of Fuzeon, which was approved last spring, but discontinued Fuzeon and added T-1249 to an unchanged individualized anti-HIV drug regimen. Phase II studies of the compound are projected to begin next year.