[LbOr19A] Enfuvirtide (T-20) in combination with an optimized background (OB) regimen vs. OB alone in patients with prior experience or resistance to each of the three classes of approved antiretrovirals (ARVs) in Europe and Australia.

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Enfuvirtide (T-20) in combination with an optimized background (OB) regimen vs. OB alone in patients with prior experience or resistance to each of the three classes of approved antiretrovirals (ARVs) in Europe and Australia.

[AUTHOR(S):] B Clotet, A Lazzarin, D Cooper, J Reynes, K Arasteh, M Nelson, C Katlama, J Chung, L Fang, J Del

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbOr19A

BACKGROUND: Enfuvirtide (T-20; ENF) is the most advanced agent in a new class of investigational ARV, the Fusion Inhibitors, that blocks gp41-mediated fusion of HIV-1 to host cells. TORO 2 (T-20 vs Optimized Regimen Only) is the second Phase III study of enfuvirtide, similar in design to TORO 1.

METHODS: Patients from 64 sites in Europe and Australia with >3 months prior experience with 3 classes of ARVs, and HIV-1 RNA >5,000 copies/mL selected an OB regimen of 3-5 ARVs based on prior history and baseline (BL) genotypic (GT) and phenotypic (PT) viral resistance. Patients were randomized 2:1 to enfuvirtide (90 mg SC BID) + OB or OB alone.

RESULTS: 504 patients were randomized, received at least one dose of study drug and had at least one post-BL assessment. Median BL HIV-1 RNA in both arms was 5.1 log₁₀ copies/mL, and overall CD4 count 98 cells/mm³. Demographics and prior ARV experience were balanced across arms; patients had prior experience of an average of 12 ARVs with almost 90% of patients having virus with 5 or more primary mutations to the 3 ARV classes. Patients in both arms used on average 4 ARVs in their OB regimen. At the 24 week primary analysis (ITT, Last Observation Carried Forward) the least squared means change from BL in viral load (covariate, phenotypic sensitivity score) were -1.43 log₁₀ and -0.65 log₁₀ copies/mL for enfuvirtide + OB and for OB alone respectively, a difference of 0.78 log₁₀ copies/mL (p<0.0001). By week 24 of the study 17% and 5% of patients discontinued from enfuvirtide + OB and OB respectively. Injection site reactions (ISRs) were experienced by 98% of patients but only 3.3% had to discontinue for these. Aside from ISRs, the safety profile was comparable across treatments and similar to previous Phase II studies.

CONCLUSIONS: Enfuvirtide provided significant viral suppression at 24 weeks when used with an OB regimen in heavily pre-treated patients, confirming the results of TORO 1.

Presenting author: B Clotet

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