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VER X VE

VER X VE.

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VER X VE

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  1. VERXVE Comparison of 48 week efficacy and safety of 400mg QD nevirapine (NVP) extended release formulation (Viramune XR) versus 200mg BID nevirapine immediate release formulation (Viramune IR) in combination with emtricitabine/tenofovir in antiretroviral (ARV) naïve HIV-1 infected patients (VERxVE) J. Gathe, JR. Bogner, S. Santiago, A. Horban, M. Nelson, P. Cahn, J. Andrade, D. Spencer, C. Yong, T. Nguyen, W. Zhang, M. Drulak and A. Quinson* *Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA

  2. Viramune 200mg immediate release (IR) is a well established component of effective antiretroviral therapy in HIV-1 infected patients Viramune 200mg IR plus emtricitabine/tenofovir (FTC/TDF) recently demonstrated similar efficacy to atazanavir/ritonavir plus FTC/TDF, with a more favourable lipid profile1 Viramune extended release formulation (Viramune XR) may increase therapeutic benefit by improving compliance through once-daily (QD) dosing VERX VE:Rationale for Viramune Extended Release (XR) Formulation • 1. Soriano V. et al. 2010 Manuscript submitted

  3. VERX VE: Objectives and Study Design Objective: • To evaluate the efficacy of Viramune XR 400 mg QD vs Viramune IR 200 mg BID, in ARV treatment-naïve, HIV–1-infected patients after 48 weeks of treatment • Study design: • Double-blind, double-dummy, non-inferiority study • 1:1 randomization to Viramune XR or Viramune IR after 14-day Viramune IR lead-in 200 mg QD dose (given to all patients) • Emtricitabine/tenofovir (FTC/TDF) fixed-dose background ARV treatment • Baseline viral load (VL) stratification (≤100,000 vs >100,000 copies/mL)

  4. Primary endpoint: Sustained virologic response at 48 weeks defined as VL <50 copies/mL prior to and at week 48, without virologic rebound or change of ARV therapy Secondary endpoints: Time-to-loss of virologic response (TLOVR) Time to new AIDS or AIDS-related progression event or death Genotypic resistance associated with virologic failure AEs, SAEs, AEs leading to discontinuation; laboratory parameters VERX VE:Study Endpoints

  5. VERX VE:Demographic Data Note: Total randomized=1068, 1011=randomized & treated (full analysis set, FAS), 2 randomized not treated, 55 DC during lead-in

  6. VERX VE: Disposition of Randomized Patients Through Week 48 *None of the deaths/events were related to study medication, as judged by the investigators

  7. VERX VE: Sustained Virologic Response at Week 48 (VL <50 copies/mL, FAS) Viramune IR Viramune XR 100 90 80.99 80 75.89 Viramune IR: 75.89% (384/506) Viramune XR: 80.99% (409/505) Adjusted difference 4.92% in favour of Viramune XR, with 95% CI of (−0.11, 9.96) Viramune XR shows non-inferiority to Viramune IR within pre-specified margin of −10% 70 Proportion of patients with Virologic Response Week 48 60 50 40 30 20 10 0 Virologic response was independent of age, gender, race or geographic region FAS = Full analysis set

  8. VERX VE: Proportion with Virologic Response by Visit (VL <50 copies/mL, FAS) 100.00 80.00 60.00 Proportion of Virologic Responders 40.00 Viramune IR 20.00 Viramune XR 0.00 6 40 0 8 48 4 12 16 2 24 32 Weeks FAS = Full analysis set

  9. VERX VE: PK Sub-study at Day 28 • Designated trial centres participated in a pharmacokinetic sub-study, involving ~25 patients from each treatment arm • Blood samples collected intensively for 24 hr following morning NVP administration in week 4 (visit 4): day 28 • Plasma NVP levels measured by tandem mass spectrometry (LC-MS/MS) • Arithmetic mean (±SD) plasma concentration of NVP following 400mg QD and 200mg BID dosing determined

  10. VERX VE: PK Sub-study at Day 28: Results (N=25) (N=24) 200mg Viramune IR BID 400mg Viramune XR QD 7000 6000 5000 Viramune Plasma (ng/mL) 4000 3000 2000 24 12 16 20 0 4 8 Time [hours]

  11. VERX VE:PK-PD Response Week 48 (FAS): Viramune XR Equivalent to Viramune IR at ≥1000ng/mL Virologic response rates stratified by geometric mean steady state (ss) trough plasma concentrations (ng/mL) LLOQ (lower limit of quantification) = 50 copies/mL FAS = Full analysis set

  12. VERX VE: Percentage Change in Lipid Profile Viramune IR vs Viramune XR at Week 48 Viramune XR demonstrated a similar lipid profile to that of Viramune IR

  13. VERX VE: AE Summary Randomized Phase, FAS *Investigator defined. Please note: No drug-related fatalities. Atherosclerosis/hypertension; tuberculosis (meningitis); two sepsis, myocardial infarction; respiratory alkalosis. FAS = Full analysis set

  14. VERX VE: Conclusions • Pivotal Trial (VERXVE) demonstrated: • Non-inferior efficacy for Viramune XR to Viramune IR • Similar safety and tolerability profiles for both formulations • The combination of Viramune IR or Viramune XR with FTC/TDF is an effective ARV treatment • PK – PD: • Similar efficacy noted across many PK strata indicating adequate trough drug exposure for Viramune XR • Consistent relative trough exposure of Viramune XR to IR across gender, region, and baseline viral-load strata • Once-daily dosing with VIRAMUNE XR provides patients with a more convenient treatment regimen with comparable efficacy and safety to VIRAMUNE IR

  15. We would like to thank all the patients and investigators for their involvement and dedicated support in this trial VERX VE: Acknowledgments

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