ICAAC In Brief

Noxafil graft vs. host data: Schering-Plough plans to submit an NDA for use of its novel triazole antifungal Noxafil (posaconazole) for prevention of invasive fungal infections (IFIs) in high-risk patients, the company says. One of the pivotals, presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, D.C. Dec. 16-19, shows significantly greater efficacy in preventing aspergillosis compared to fluconazole. In the 600-patient trial of stem cell transplant recipients with graft-versus-host disease, seven Noxafil-treated patients (2%) developed aspergillosis compared to 21 for fluconazole (7%) (p=0.006). The study poster notes that Noxafil was "as effective" as fluconazole in preventing IFIs other than aspergillosis. A total of 16 Noxafil patients (5%) developed IFI of any kind compared to 27 in the fluconazole group (9%) (p=0.07). Noxafil has been "approvable" since June for refractory invasive fungal infections (¹ Pharmaceutical Approvals Monthly July 2005, In Brief)....

J&J TMC-114 goes to ICAAC, then FDA: Johnson & Johnson's Phase IIb POWER 2 trial for HIV protease inhibitor TMC-114 shows that 62% of patients in the highest dose arm (600 mg/100 mg) achieved at least a 1 log viral load reduction compared to 14% in the control group, the firm discloses at ICAAC Dec. 19. An NDA seeking accelerated approval was submitted Dec. 23 ( ² (Also see "Year-End Submission Rate Stabilizes In 2005 As NDA Approvals Drop" - Pink Sheet, 15 Jan, 2006.) ). In POWER 2, TMC-114 boosted with ritonavir was evaluated in patients treated with at least one PI, one non-nucleoside reverse transcriptase inhibitor or one NRTI. After 24 weeks of treatment, 39% of patients in the TMC-114/ritonavir high-dose group reached undetectable virus levels compared to 7% in the control. TMC-114 currently is in Phase III trials for both treatment-experienced and treatment-naïve HIV patients; an expanded access program began in October 2005....

Tanox entry inhibitor Phase II data: Tanox will advance its entry inhibitor TNX-355 into Phase III studies in the second half of 2006, the firm says. Tanox "is planning to confer with the FDA in early 2006 to determine next steps for development" of the monoclonal antibody, the firm reported Dec. 17. At ICAAC, the firm unveiled positive 24-week data from a Phase II placebo-controlled study looking at two TNX-355 doses. In combination with an optimized background regimen, TNX-355 at 15 mg/kg and 10 mg/kg doses resulted in a mean decrease in viral load of 0.97 log and 1.20 log, respectively (p<0.001). Time to virologic failure also was significantly better in both TNX-355 arms compared to placebo. Tanox says it "will continue the Phase II trial through its planned 48-week duration"; responders will continue on to a 96-week extension....

GSK/Vertex brecanavir on track for Phase III: GlaxoSmithKline and Vertex expect their HIV protease inhibitor brecanavir to enter Phase III studies this year. The firms presented positive 24-week data at ICAAC from a Phase II, open-label study showing 81% of patients achieving under 400 HIV RNA copies and 77% reaching undetectable viral load levels (<50 copies). Brecanvir (formerly GW640385/VX-385) is likely to be useful in resistant HIV strains, the firms state....

Dynavax Heplisav vs. GSK Engerix-B: Dynavax' toll-like receptor 9 agonist-based hepatitis B vaccine Heplisav shows significantly better seroprotection against HBV compared with GlaxoSmithKline's Engerix-B vaccine, Dynavax reports at ICAAC. In a Phase II/III study in 88 seronegative patients, Heplisav showed 100% seroprotection compared to 90.5% in the Engerix-B group (p=0.034) at four weeks. At week 50, subjects receiving Heplisav maintained their 100% levels, while the Engerix-B group declined to 86% (p=0.009). Heplisav entered Phase III in June 2005 with the initiation of a 400-patient Phase III study in 40-70-year-olds; a second Phase III trial is slated to begin in the first half of 2006. "We are initially focusing on patients with chronic renal failure who are either about to undergo hemodialysis or are already on hemodialysis," Dynavax said. HIV-infected patients will be another target for the HBV vaccine....

Theravance telavancin skin infection data: Theravance's injectable lipoglycopeptide antibiotic telavancin shows significantly better microbiologic eradication of methicillin-resistant Staphylococcus aureus (MRSA) skin and skin structure infections compared to standard treatment, Theravance reports Dec. 18 at ICAAC. In the firm's 195-patient, Phase II FAST 2 trial, eradication of MRSA infections was 92% with telavancin vs. 68% (p=0.043). Cure rates were similar for telavancin and standard care (anti-Staph penicillins or vancomycin) in MRSA patients, with telavancin showing a 96% success rate in MRSA compared to standard care's 90%. Infection eradication also was not significantly better in the study's overall population - including non-MRSA patients - (92% vs. 78%; p=0.066). Telavancin currently is in Phase III for complicated skin and skin structure infections. Pfizer's lipoglycopeptide dalbavancin has been "approvable" for the same indication since September (³ Pharmaceutical Approvals Monthly December 2005, p. 5)....