1 / 17

Back Up Slides

Back Up Slides. July 29, 2008. Screening Evaluations and Exclusions. Exclusions for General Safety

Jimmy
Télécharger la présentation

Back Up Slides

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Back Up Slides July 29, 2008

  2. Screening Evaluations and Exclusions Exclusions for General Safety • Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (included but not limited to tuberculosis and atypical mycobacterial disease, granulomatous disease on chest X-ray, Hepatitis B and C, and herpes zoster), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within four weeks of screening or oral antibiotics within two weeks prior to screening. • Primary or secondary immunodeficiency (history of or currently active) • Laboratory Exclusion Criteria • White Blood Cells < 3000/mm3 • Absolute Neutrophil Count < 2000/mm3 • Absolute Lymphocyte Count < 500/mm3 • Positive Hepatitis BsAg or Hepatitis C Antibody

  3. 8 mg/kg TCZ + MTX 4 mg/kg TCZ + MTX Placebo + MTX 100 90 80 70 60 50 40 30 20 10 0 DMARD IR & Anti-TNF IR:Long-Term Response Over Time % ACR50 Responders WA17822 WA18062 TCZ 8 mg/kgOpen-label TCZ 8 mg/kgOpen-label

  4. Immunogenicity Summary of Combined 6-Month Controlled and LTE Studies • Total of 59/3353 (1.8%) developed anti-TCZ HAHAs • 12 patients experienced an infusion-related reaction and were positive for anti-TCZ antibodies • 5 of these experienced a serious event or event leading to WD • 38/3353 (1%) developed neutralizing anti-TCZ HAHAs (blocks binding of TCZ to s-IL-6r) • Neutralizing antibody positive patients had a similar safety profile to patients who did not develop anti-TCZ HAHAs • No association between neutralizing antibody development and loss of clinical response • 1/38 patients discontinued due to lack of efficacy

  5. Neutrophil Time Course in Healthy Volunteers

  6. Sample Size and RR *Solomon et al. 2006 **Smitten et al. 2008 ***Wolfe and Michaud 2007 ****UHC analysis ****Beyeler et al. 1997

  7. Percentage of Patients Experiencing a Serious Infection

  8. or SA-MTP TCZ-bio TCZ-Dig Pab-<DIG>POD Pab<TCZ Assay to screen for AB positive human serum specimens • Assay principle: bridging ELISA • Sensitivity: fulfills regulatory expectations • TCZ immobilization with two distinct biotinylisation labeling processes (labeled at lysines and at the carbohydrates) to avoid epitope masking • Measures free anti TCZ AB, isotype independent • Adapted as confirmation assay: TCZ spiked in screening positive samples to quench the signal

  9. DMARD Inadequate Responders: Summary of Reasons for Not Achieving an ACR70 Response in Patients Who Achieved DAS28 < 2.6 at Week 24 ITT A = Phy VAS B = Pt VAS C = Pain VAS D= HAQ E = CRP

  10. Planned Education Materials / Tools

  11. Mean age: 61 years (45-82) Mean duration RA*: 12.6 years (0.5-33) Mean number doses TCZ: 20 (2-63) Sex: 10 F, 4 M Medications Corticosteroids: 10 NSAIDs: 9 Unknown: 2 LGI Perforations (RA): n=14Roche and Chugai * Disease duration unknown for 2 patients

  12. Mean age: 59 years (49-76) Mean dur RA: 22 years (11-42, Roche only) Mean doses TCZ: 21 (2-35) Sex: 6 F Medications Corticosteroids: 5 NSAIDs: 6 UGI Perforations (RA): n=6Roche and Chugai

  13. Post-marketing surveillance of ACTEMRA®in RA in Japan • ACTEMRA® was approved for RA on April 16, 2008 • All patients survey – Routinely required by the Japanese regulatory agency. • Target number of patients: 3,000 in total • Observation period: 6 months • Focus on Adverse Drug Reactions and Serious ADRs • 3-year long-term follow up • SAEs of special interests, including Death, Serious Infection (1 year), CV events, Malignancy, and GI perforation • Current Status (as of July 11, 2008) • Number of registered patients: 1,620 • Estimated number of patients treated with TCZ: 1,424 • No new safety signal has been detected.

  14. Patient 64069/4798(WA17824 and WA18696)

  15. Salient summary points • Inflammation in man  lipids (LDL-c, HDL-c, TG) • post MI, post surgery • Sepsis, trauma, ITU • Cancer, RA •  inflammation   lipids • Inflammation resolution/ suppression •  lipids (HDL-C and LDL-C, plus trigs) • In RA TNF-blockers>> DMARDS • Responders >> non-responders • Yet TNF-blockers (responders)  CVD risk

  16. Review of anti-TNF – lipid studies Infliximab 30 Adalimumab 19.1 19.5 20 Change in LDL-cholesterol from baseline (mg/dL) 12.9 11.7 10 3.1 3.0 33 n= 59 50 19 56 20 0 1 2 3,4 5,6 7 8 DMARD failures Active RA 1. Allanore Y, et al. Clin Chim Acta 2006; 365:143–148. 2. Kiortsis DN, et al. J Rheumatol 2006; 33:921–923. 3. Brulhart L, et al. Ann Rheum Dis 2006; 65:1255–1257. 4. Tam LS, et al.ACR 2005. 5. Allanore Y, et al. ACR 2004. 6. Allanoe Y, et al. EULAR 2004. 7. Voskuyl AE, et al. EULAR 2002. 8. Popa C, et al. Ann Rheum Dis. 2005; 64:303–305.

  17. Review of anti-TNF – lipid studies • Popa et al ARD (2007) Infliximab 6/12 •  TC > HDL-C • ↓  DAS   lipids • Peters (2007) ARD 48 week trial infliximab • ↓  DAS   TC and HDL-C

More Related