Data presented today at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy were from the 24-week primary efficacy and safety analysis of the POWER 2 study, a randomized trial of TMC114 boosted with ritonavir (TMC114/r) in patients with experience of at least 1 PI, 1 NNRTI and 1 NRTI and had 1 or more primary PI mutations.

The results showed that 62% of patients achieved a reduction in viral load (plasma HIV RNA) of 1 log₁₀ or more in the highest TMC114/r dose group, 600mg/100mg BID, compared to 14% in the control group. A total of 278 patients were randomized to receive optimized background regimen (OBR) plus one of four doses of DRV/r (400mg/100mg QD; 800mg/100mg QD; 400mg/100mg BID; 600mg/100mg BID) or OBR plus investigator-selected control PI(s).

At 24 weeks, the percentage of patients reaching undetectable virus levels (<50 copies/ml) was 39% in the highest TMC114/r dose group compared with 7% in the control arm. This study will continue to 144 weeks.

Based on the 24-week results from POWER 1 and POWER 2, the selected dose for treatment-experienced patients in Phase III trials is TMC114/r 600mg/100mg BID.

"These preliminary results in these treatment-experienced patients with highly resistant virus are encouraging," said Dr. Timothy Wilkin, Cornell University, New York, NY who presented the data at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy. "The reduction in viral load observed in this trial demonstrated the antiviral activity of TMC114, and the accompanying rise in CD4 cells is clinically meaningful."

The most common treatment-emergent adverse events (AEs) were headache and nausea, which were each 17% across all TMC114/r arms compared with 17% and 9% respectively in the control arm. Overall, 15% of TMC114/r and 8% of control patients reported at least one serious AE (SAE).

Dr. Daniel Berger’s oral presentation on TMC114/r in POWER 2 focused on the safety aspects of the drug regimen (see below).

Adverse Events in POWER 2 Trial

• The incidence of AEs (any grade) was comparable between TMC114/r and control patients.
  
  
• Overall, 15% of TMC114/r and 8% of control patients reported at least one serious AE (SAE). This likely reflects the high discontinuation rate and lower treatment exposure in the control group.
  
  
• The most common SAE was pneumonia, reported in 2% of TMC114/r and 4% of control patients. No dose-response relationship was observed for SAE frequency.
  
  
• Six patients who received TMC114/r died. Causes of death were staphylococcal sepsis, lymphoma, lung, adenocarcinoma, acute myeloid leukemia, congestive cardiomyopathy and illicit drug overdose. Investigators considered five deaths as unrelated and one as doubtfully related to study medication (lung adenocarcinoma).
  
  
• Without correcting for drug exposure, the observed incidence of commonly reported AEs was generally similar between all TMC114/r groups and control.
  
  
• The most common treatment-emergent AEs in the TMC114/r groups and occurring in at least 10% of patients were headache (17%), nausea (17%), diarrhea (16%), fatigue (16%) and insomnia (10%). Similarly, headache (17%) and diarrhea (16%) were the two most common treatment-emergent AEs observed in the TMC114/r groups in the POWER 1 trial.3 Overall, no dose-response relationship was observed for any AE.
  
  
• When exposure to treatment was corrected for, the overall incidence of AEs was lower in the TMC114/r groups than inthe control arm
  
  – thus, the incidence of headache and fatigue was substantially lower in the TMC114/r groups than in the control group (28.3 vs 43.4 events/100 patient years of exposure and 25.4 vs 48.2 events/100 patient years of exposure, respectively)
  
  – likewise, the incidence of diarrhea was markedly lower for TMC114/r-treated patients than in control patients (25.4 vs 57.8 events/100 patient years of exposure)
  
  – for nausea, no apparent difference was found between TMC114/r and the control group (28.3 vs 24.1 events/100 patient years of exposure).

TMC114 boosted with low-dose ritonavir (TMC114/r) is in Phase III clinical trials in both treatment-experienced and treatment-naïve HIV-1 infected patients.

12/20/05

Source
Tibotec

References 

T Wilkin and others. TMC114/r Superior to Standard of Care in 3-class-experienced Patients: 24-week Primary Analysis of the POWER 2 Study (TMC114-C202). Abstract 2860 (oral). 45^th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. December 16-19, 2005. Washington, DC.

D Berger and others. . TMC114/r in 3-class-Experienced Patients: 24-wk Primary Safety Analysis of POWER 2 study (TMC114-C202). Abstract 3173 (poster). 45^th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. December 16-19, 2005. Washington, DC.