1 / 21

Safety Review

Safety Review. Sources of Safety Information. BLA 125397 (Applicant’s data) 1993-2007: Voluntary questionnaires 2008-present: SCTOD FDA Dockets Literature Search The COBLT Study Prospective clinical study of safety and efficacy of unrelated donor cord blood transplantation

chaney
Download Presentation

Safety Review

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. Safety Review

  2. Sources of Safety Information • BLA 125397 (Applicant’s data) • 1993-2007: Voluntary questionnaires • 2008-present: SCTOD • FDA Dockets • Literature Search • The COBLT Study • Prospective clinical study of safety and efficacy of unrelated donor cord blood transplantation • Sponsored by the NHLBI

  3. Review Strategy • Characterize the safety profile of the applicant’s product • Units manufactured using the method intended for licensure • TNC dose >2.5 x 107/kg • Summarize the safety information from the additional public sources • Emphasis on product-related outcomes • Infusion reactions, delayed neutrophil recovery, graft failure, early mortality

  4. Agenda • Describe the datasets used • Summarize safety outcomes • Summarize infusion reactions

  5. Datasets Used In FDA Analyses • BLA 125397 (Applicant) • Datafile for 3619 patients transplanted with 3946 cord blood units • Limited to 409 patients transplanted 2007 to 2011 with 432 cord blood units manufactured using the method intended for licensure • Pooled Dataset (Public Information) • NYBC: 550 patients transplanted 1993-1998 • COBLT: 356 patients transplanted 1999-2004 • NMDP: 577 patients transplanted 2000-2006

  6. Patient Demographics

  7. Transplant Characteristics

  8. Agenda • Describe the datasets used • Summarize safety outcomes • Summarize infusion reactions

  9. Hematopoietic RecoveryTNC Dose >2.5 x 107/kg * Includes death, 2nd transplantation or autologous recovery for patients surviving at least 14 days without neutrophil recovery For all patients in the pooled dataset: • Primary graft failure was associated with TNC dose, degree of HLA mismatch and diagnosis • Time to ANC>500 was associated with TNC dose and degree of HLA mismatch

  10. Hematopoietic Recovery by Diagnosis(Pooled Dataset -TNC Dose >2.5 x 107/kg)

  11. Day 100 MortalityTNC Dose >2.5 x 107/kg For all patients in the pooled dataset: • Day-100 Mortality was associated with TNC dose, degree of HLA mismatch, diagnosis and gender.

  12. Additional Outcomes of Interest ∙ GVHD in patients who received a TNC dose >2.5 x 107/kg. For all other outcomes, patients receiving any TNC dose are considered. +From The COBLT Study dataset only.

  13. Safety Outcomes Overview • Applicant’s Data (TNC Dose >2.5 x 107/kg) • Primary graft failure in 14% • Median time to neutrophil recovery is 20 days • Day-100 mortality is 25% • Mortality due to graft failure is 3.9% • Transmission of a genetic disorder is rare • Additional Information • Donor cell leukemia and transmission of infections are additional rare events. • Engraftment syndrome is an additional common event.

  14. Agenda • Describe the datasets used • Summarize safety outcomes • Summarize infusion reactions

  15. Infusion Reaction Characterization • Applicant’s Data (n=244 infusions) • Data questionnaire: Requested information on any SAE or any event that required intervention • SCTOD: Requested information on 17 specific adverse events and SAEs • No grading • The COBLT Study (n=523 infusions) • Prospectively requested information on 13 specific adverse events with grading by NCI CTC criteria • Any SAE also graded and reported.

  16. Infusion Reactions

  17. Infusion Reactions

  18. Infusion Reactions - Cardiopulmonary

  19. Cardiopulmonary SAEs • Spectrum of signs and symptoms includes hypertension, cardiomyopathy, pulmonary edema, acute respiratory distress and acute renal failure. • Applicant reports 4 infusion-related SAEs (0.1%) • None of the reports involved units manufactured with the method intended for licensure • Four (0.8%) such SAEs were also reported in The COBLT Study dataset. • Five additional published cases

  20. Composition of Prepared Unit ∙ Prepared according to applicant’s instructions. The instructions do not include an infusion rate. Dextran 40 • Side effects include pulmonary edema, congestive heart failure, acute renal failure, bleeding disorders and anaphylactoid reactions • Recommended dose is 5-10 mL/kg over 12-24 hours (available as a 10% solution)

  21. Infusion Reactions Overview • Applicant’s Data (TNC Dose >2.5 x 107/kg) • Reported infusion reaction rate is 18% • Serious cardiopulmonary events in 0.1% • The most common infusion reactions are hypertension (14%), nausea (5%), vomiting (4%), and hypoxemia (3%) • Additional Information • Reported infusion reaction rate is 65% • Serious cardiopulmonary events in 0.8% • Severe allergic reactions occurred in 0.2%.

More Related