Sempre più promettenti i dati presentati su questi nuovi farmaci: l’IP TMC 114 e l’NRTI Reverset. Delta conterrà un report dettagliato di queste presentazioni.

Presentati i risultati finali a 24 settimane dello studio di fase IIb POWER 1 riguardante il TMC 114/r su 318 pazienti pre-trattati. Ottimi i risultati virologici e sorprendentemente positivi quelli immunologici. Anche sugli effetti collaterali il farmaco sembra molto promettente.

The purpose of this study is to determine the efficacy of TMC114/ritonavir in 3-class experienced patients in a randomized, controlled, international, multi-center phase IIb efficacy/safety study.

Three-class experienced patients on a stable PI-regimen with VL>1,000 copies/ml were randomized to one of four TMC114/r doses, or investigator-selected PI(s). Patients received optimized background regimen (OBR) (>2 NRTIs with/without enfuvirtide (T20). All patients had >1 primary PI mutation. All analyses were intent-to-treat. This is the abstract in the program, and the oral presentation will be presented at the Late Breakers Session on the last day of the conference, and will contain additional information.

RESULTS

318 patients had received a mean of 4 prior PIs. Baseline values were comparable across all groups: mean VL was 4.48 log10 copies/ml and CD4 was 179 cells/mm3; 13%, 31%, and 56%, respectively had 1, 2, or >3 primary PI mutations.

–During study, 10% of TMC114/r patients discontinued vs 62% of controls (control discontinuations mainly occurred for virologic failure).

Efficacy data are presented for the TMC114/4 dose selected for treatment-experienced patients (600/100 mg bid, n=65), vs controls, n=63).

–At week 24, the mean CD4 increase from baseline was 124 cells/mm3 for TMC114/r vs 20 cells/mm3 for control (P<0.001).

–The primary endpoint of >1 log10 VL reduction from baseline was achieved in 77% of TMC114/r patients vs 25% for control (p<0.001).

–Mean VL decrease for TMC114/r was 2.03 vs 0.63 log10 copies/ml for control (p<0.001).

–VL <50 copies/ml occurred in 53% of TMC114/r patients vs 18% of controls (p<0.001).

–VL <50 copies/ml was achieved in 63% of the 19 TMC114/r patients who received T20 in their OBR (previously T20 naïve) vs 56% of the 34 TMC114/r patients who did not receive T20.

Safety data results were also reported. During the study 62% of controls discontinued, 54% for virologic failure, 6% for adverse events. Ten percent of TMC114/r patients discontinued, 5% for AEs. Incidence of serious AEs was equivalent for TMC114/r and control groups (14%). Most AEs and lab abnormalities were mild-to-moderate in severity with similar incidence across all groups. Safety profile in HCV/HBV-HIV coinfected patients (n=31/255) was comparable to the overall population.

600/100mg dose group; control group
Any AE: 92%; 94%
Any grade 3-4 AE: 23%; 29%
Grade 2-4 triglycerides, total cholesterol: 12.3%, 10.8%; 28.6%, 1.6%
Grade 3-4 ALT (AST): 1.5%, 0; 3.2%, 4.8%

Presentati i risultati finali a 16 settimane dello studio di fase IIb RVT-203 riguardante il Reverset (D-d4FC ) su 120 pazienti pre-trattati. Buoni i risultati virologici. Già, però, la molecola ha un “alert” sull’uso concomitante con didanosina.

Results: 199 pts enrolled at 25 sites; currently, 120 completed >16 wks of therapy. Mean baseline VL = 4.5 log10, presence of M184V: 60%, M41L: 60%, 4-6 TAMs: 50%, K65R: 6%.

After 2 wks, mean VL changed by +0.007, -0.5, -0.3, and -0.7 log10 for placebo, 50, 100, and 200 mg groups respectively.

Pts on 200 mg with 0-3 TAMs had 2-wk VL drop of 0.8 log10, with 4-6 TAMs a 0.6 log10 drop.

Pts with M41L, M41L+L210W or w/o M41L showed similar VL decreases (0.7 log10).

Pts with K65R or M184V + TAMs had more variable responses (mean 0.4 log10 drop); >20% pts had > 1 log10 drop.

33% pts didn’t optimize at wk 2. Of these, current data shows stable VL decrease of about 0.6 log10 at wk 16 on 200 mg RVT.

AEs generally mild, included headache, fatigue and GI disorders.

In 35 subjects taking RVT with ddI, 12 (34%) had grade 4 hyperlipasemia (alcool use ?), usually occurring after >12 wks of treatment. Among pts not on ddI, asymptomatic grade 4 lipase seen in 5.4% of pts on 200 mg RVT vs. 3.1% on placebo. Pancreatitis seen in 3 pts on RVT+ddI+TDF: 1 pt on ddI 250mg/TDF 450mg, 1 pt on ddI 400mg/TDF 300mg; all resolved off drugs.

Conclusions: RVT 200 mg is active in ARV-experienced pts and generally well tolerated. Because of the risk of elevated lipase and pancreatitis, RVT should not be used with ddI. Data support continued development of RVT.