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Financial Disclosures

Financial Disclosures. JM Goodrich, E van der Ryst, J Sullivan, M Westby, H Mayer: are full-time employees of Pfizer Global Research and Development

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Financial Disclosures

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  1. Financial Disclosures • JM Goodrich, E van der Ryst, J Sullivan, M Westby, H Mayer: are full-time employees of Pfizer Global Research and Development • M Saag: Has received grant/research support from Achillion Pharmaceutica, Boehringer-Ingelheim, Gilead Sciences, GlaxoSmithKline, Merck, Panacos, Pfizer/Agouron, Progenics, Roche Laboratories, Serono, Tibotec, Trimeris, and Vertex; and consulting fees from Achillion Pharmaceutical, Avexa, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Monogram Biosciences, Panacos, Pfizer/Agouron, Progenics, Roche Laboratories, Tanox, Tibotec/Virco, Trimeris, and Vertex • G Fätkenheuer:Has received consulting fees from Pfizer • B Clotet: Has received consulting fees and lecture fees from Gilead, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Tibotec-Jansen, Boehringer Ingelheim, Pfizer, Abbot, Merck, and Panacos • N Clumeck: Has received reimbursement for either/or: attending a symposium; a fee for speaking; a fee for organizing education; funds for research; fees for consulting from various pharmaceutical companies including, Abbott, Boehringer, Merck Sharp & Dohme, Roche, GlaxoSmithKline, Tibotec GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  2. 45th IDSA San Diego, USA, October 4–7, 2007 Presentation LB-2 48-Week Safety and Efficacy of Maraviroc in Combination with Optimized Background Therapy (OBT) for the Treatment of Antiretroviral-Experienced Patients Infected with Dual/Mixed-Tropic HIV-1 JM Goodrich1, M Saag2, E van der Ryst3, G Fätkenheuer4, B Clotet5, N Clumeck6, J Sullivan3, M Westby3, and H Mayer1 1Pfizer Global Research and Development, New London, USA; 2University of Alabama at Birmingham, USA; 3Pfizer Global Research and Development, Sandwich, UK; 4University of Cologne, Cologne, Germany; 5University Hospital Germans Trias i Pujol, Barcelona, Spain; 6St Pierre University Hospital, Brussels, Belgium GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  3. Background • Maraviroc, a CCR5 antagonist, is active against R5 but not X4 or dual-tropic HIV‑1 • A4001029 is a double-blind, placebo-controlled, Phase 2b study investigating the safety and efficacy of maraviroc in treatment-experienced patients with non-R5 HIV-1 • At 24 weeks1, in treatment-experienced patients with D/M-tropic HIV-1 and advanced disease: • Maraviroc + OBT was generally well tolerated • HIV-1 RNA changes were not significantly different between either MVC + OBT group and PBO + OBT • Maraviroc + OBT was associated with greater increases in CD4+ cell count than PBO + OBT OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of RTV not counted as an ARVD/M = dual/mixed 1. Mayer H et al. XVI IAC 2006; Abstract THLB0215 GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  4. A4001029: Phase 2b Pilot Study Evaluating the Safety of Maraviroc in Patients with Non-R5 HIV-1 Maraviroc (150 mg* BID) + OBT Screening and randomization Maraviroc (150 mg* QD) + OBT Placebo (PBO) + OBT Screening(4–6 weeks) 0 24 wk 48 wk Primary efficacyendpoint • Stable pre-study ARV regimen, or no ARVs for ≥ 4 weeks • Dual-class resistance and/or ≥ 3 months’ experience with ≥ one ARV from three classes • Patient eligibility criteria: • X4 or D/M-tropic HIV-1, or indeterminate tropism due to repeated assay failure • At least one active drug in OBT • HIV-1RNA ≥5,000 copies/mL OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of RTV not counted as an ARV) *Patients receiving a PI (except TPV) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  5. Baseline Characteristics Includes all treated patients with non-R5 virus at screening who received at least one dose of study medication * Primary study population; all treated patients with D/M-tropic virus at screening who received at least one dose of study medication NP/NR - not phenotyped/not reported D/M - dual/mixed tropic GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  6. Baseline Characteristics—Primary Study Population Includes all treated patients with D/M-tropic virus at screening who received at least one dose of study medication * Mean of up to three pre-dose assessments (screening, randomization, and baseline)†Data missing for four patients‡Data missing for one patient in each treatment group GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  7. PBO + OBT (N=58) MVC QD + OBT (N=57) Study week MVC BID + OBT (N=52) 241 48 0.0 -0.5 Mean change in HIV-1 RNA from baseline (log10 copies/mL) -0.62 -0.84 -0.91 -1.0 -0.97 -1.11 -1.20 Difference: +0.23* (97.5% CI: -0.35, +0.81) Difference: +0.06* (97.5% CI: -0.53, +0.64) -1.5 Difference: -0.26*(97.5% CI: -0.86, +0.33) Difference: -0.23(97.5% CI: -0.83, +0.36) Mean Change in HIV-1 RNA from Baseline Includes all treated patients with D/M-tropic virus at screening who received at least one dose of study medication HIV-1 RNA value imputed as baseline if patient discontinued before 48 weeks*Treatment difference vs PBO + OBT 1. Mayer H, et al. IAC 2006; Abstract THLB0215 Study A4001029–Week 24 & 48 GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  8. Percentage of Patients with Undetectable HIV-1 RNA Over 48 Weeks Includes all treated patients with D/M-tropic virus at screening who received at least one dose of study medication PBO + OBT (N=58)MVC QD + OBT (N=57) MVC BID + OBT (N=52) <400 copies/mL <50 copies/mL 31% 31% 27% 27% 22% Patients (%) 21% 22% 25%* 24%† 21% 18% 16% Time (weeks) Time (weeks) HIV-1 RNA value imputed as baseline if missing or if patient discontinued before 48 weeks* MVC QD + OBT; † PBO + OBT Study A4001029–Week 48 GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  9. Subjects with Viral Load <400 copies/mL and <50 copies/mL at Week 48 by OSS* at Screening *OSS - overall susceptibility score, a reflection of the number of active drugs in the OBT Study A4001029–Week 48 GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  10. PBO + OBT (N=54) 150 MVC QD + OBT (N=57) MVC BID + OBT (N=52) 100 78 65 62 60 51 50 36 0 Mean Change from Baseline in CD4+ Count Includes all treated patients with D/M-tropic virus at screening who received at least one dose of study medication Difference: +28*(95% CI: –5, +61) Difference: +27*(95% CI: +1, +52) Difference: +15*(95% CI: –18, +47) Difference: +24*(95% CI: –1, +49) Mean change from baselinein CD4+ count (cells/mm3) † 241 48 Study week Last observation carried forward*Treatment difference vs PBO + OBT †Data missing for four patients1. Mayer H, et al. IAC 2006; Abstract THLB0215 Study A4001029–Week 24 & 48 GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  11. Summary of Week 48 Safety Results Includes all treated patients with non-R5 virus at screening who received at least one dose of study medication AEs = adverse events; SAEs = serious adverse events*Includes deaths reported up to 28 days after stopping study drugNo deaths or malignancies were related to study drug according to the investigator Study A4001029–Week 48 GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  12. Number of Category C Events Includes all treated patients with non-R5 virus at screening who received at least one dose of study medication • No Category C malignancies (Kaposi’s sarcoma or Hodgkin’s lymphoma) were reported • Patients who experienced a Category C event had a lower median CD4+ count and slightly higher median HIV-1 RNA at baseline vs those who did not Study A4001029–Week 48 GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  13. 50 40 30 20 10 0 ISR Rash Cough Fatigue Nausea Vomiting Diarrhea Upper RTI Headache Incidence of Adverse Events Occurring in ≥10% of Patients in Any Group, Unadjusted for Exposure Includes all treated patients with non-R5 virus at screening who received at least one dose of study medication PBO + OBT (N=62) MVC QD + OBT (N=63) MVC BID + OBT (N=61) Patients (%) ISR = injection site reaction; RTI = respiratory tract infection Study A4001029–Week 48 GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  14. ALT = alanine transaminase; AST = aspartate transaminase * Total patients evaluated for each laboratory parameter†Upper limit of normal ‡ Data missing for 1 patient Maximum Liver Function Test Values Over 48 Weeks Without Regard to Baseline Study A4001029–Week 48 GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  15. A4001029: Summary of 48-Week Analysis 48-week results were consistent with 24-week findings: • Maraviroc (BID or QD) + OBT was generally well tolerated • The safety profile of MVC + OBT was similar to PBO + OBT • No new or unique safety findings emerged • Maraviroc + OBT was not associated with an increase in LFT abnormalities, Category C events, malignancies, discontinuations due to AEs, or deaths compared to PBO + OBT • There was no evidence at Week 48 of an adverse effect on viral load or CD4+ cell counts when MVC (QD or BID) was added to OBT, compared to PBO + OBT, in treatment-experienced patients with D/M-tropic HIV-1 and advanced disease GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  16. Acknowledgments • Patients who participated in the study • Investigators and study site staff • Colleagues from Monogram Biosciences: J Whitcomb, E Coakley, C Petropoulos • Colleagues from Pfizer: S Felstead, M McHale, J Sullivan, D Lindell, D Paige, S Nuttall GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

  17. Australia: David Cooper, Jennifer Hoy, Richard Moore, Anthony Allworth, Neil Bodsworth, Cassy Workman Belgium: Michel Moutschen, Jean Goffard, Bernard Vandercam, Nathan Clumeck Canada: Kevin Gough, Francois Laplante, Benoit Trottier, Christos Tsoukas, Sharon Walmsley, Richard Lalonde, Ethan Rubinstein Germany: Lutwinus Weitner, Keikawus Arasteh, Andreas Plettenberg, Jan van Lunzen, Gerd Faetkenheuer Netherlands: Andy Hoepelman Spain: Bonaventura Sala, Felix Gutierrez, Pere Pedrol, Jose Arribas, Antonio Rivero Switzerland: Milos Opravil UK: Martin Fisher, Clifford Leen, Philippa Easterbrook, Mark Nelson USA: Bisher Akil, Paul J Cimoch, Charles Farthing, Stephen Follansbee, Eliot Godofsky, David Henry III, Frederick Cruickshank, Robert Myers Jr., Gerald Pierone Jr., Jayashree Ravishankar, William Robbins, Michael Saag, Kunthavi Sathasivam, Lawrence Schwartz, Silver Sisneros, Louis Marshall Sloan, Corklin Steinhart, Melanie Thompson, William Towner Jr., David Wheeler, Sally Williams, Bienvenido Yangco, Barry Zingman, Robert Bolan, Edwin DeJesus, Jerome Ernst, Shawn Hassler, Stephen Hauptman, Joseph McGowan, Bruce Rashbaum, Stephen Becker, Nicholaos Bellos, Trevor Hawkins, Daniel Klein, Jason Leider, Daniel Skiest, Roy Steigbigel, Jorge Rodriquez, Alfred Burnside Jr A4001029: Investigators GoodrichJMet al. 45th IDSA 2007; Presentation LB-2

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