Cardiac Safety Research Consortium

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CSRC Think Tank: Factor XI Workshop

May 21, 2024

Welcome and Introduction
Norman Stockbridge ( U.S. FDA CDER); Dan Bloomfield (Anthos)
Overview of the CSRC
Jonathan Seltzer (CSRC) View Slides
Session 1:  Overview of Factor XI 
Moderators:  Brandon Atkins (Merck), Aaron Kithcart (Regeneron), Dave Gailani (VUMC)
  1. Factor XI biology & inhibition and preclinical validation : Dave Gailani (VUMC)
    Preclinical Studies/Animal Models View Slides Here
    Hemostasis sparing / uncoupling hemostasis and thrombosis
  2. Epidemiology and clinical phenotyping with FXI-deficient individuals : Jean Connors (BWH) View Slides Here
  3. Human genetic data supporting Factor XI as a target Discuss genetic studies and data: Lori Morton (Regeneron Genetics Center) View Slides Here
  4. Novel molecules (with different MOAs) targeting Factor XI; Meta analysis of Ph2 studies (TKR); Biomarkers of activity & Surrogates/ Assays to estimate the PD effects of FXI/FXIa inhibition : Jeff Weitz (McMaster) View Slides Here
  5. Panel Discussion: PANELISTS – Brandon Atkins (moderator); Aaron Kithcart (moderator); Dave Gailani (moderator); Jean Connors; Lori Morton; Jeff Weitz; Erik Tucker; Scott Berkowitz (FDA)

BREAK

Session 2:  Factor XI Development Programs 
Moderators: Robert Harrington (Weill Cornell), John Strony (JNJ) 
  1. Evolution of anticoagulation from warfarin to DOACs to FXI inhibitors – Christian Ruff (TIMI Study Group) View Slides Here
  2. Potential indications for FXI inhibitors and Phase 3 indications:   Industry, Academic and Regulatory Perspectives –  Sameer Bansilal (Bayer), Marc Bonaca (CPC Clinical Research) View Slides Here
  3. What is the potential role of FXI inhibition in – Jordan Pomeroy (FDA) View Slides Here. a. Secondary stroke prevention – Mike Sharma (McMaster) View Slides Here b. Atrial fibrillation – Manesh Patel (Duke) View Slides Here c. Patient deemed unsuitable for anti-coagulation – Bruce Hug (Anthos) View Slides Here d. Renal dysfunction and dialysis – Wolfgang Winkelmayer (Baylor) View Slides Here e. AMI – Mike Gibson (BCRI) View Slides Here f. Cancer-associated thrombosis Jeff Weitz (McMaster) View Slides Here
  4. Regulatory Science Perspective:  Lessons Learned from DOACs relevant to Factor XI – Jordan Pomeroy (FDA) View Slides Here
  5. Panel Discussion : PANELISTS- Robert Harrington (moderator); John Strony (moderator); Jordan Pomeroy; Mike Sharma; Manesh Patel; Mike Gibson; Robert Giugliano (TIMI); Roxana Mehran (Mount Sinai)
Session 3:  Benefit Risk Safety and Effectiveness–Consensus Endpoints of Interest 
Moderators: Norman Stockbridge (FDA), Dan Bloomfield (Anthos)
  1. Patient relevant bleeding:  Is minor bleeding on anticoagulants really minor?  Leslie Lake (Nat’l Blood Clot Alliance)
    View Slides Here
  2. Patient/Physician Preferences (Academic) – Shelby Reed (Duke) View Slides He
  3. Patient/Physician Preferences (Industry) – Bennett Levitan (JNJ) View Slides Here
  4. Benefit/risk assessment in SPAF – integrating stroke prevention and bleeding in a non-inferiority study (Industry
    perspective) – Elliot Barnathan (JNJ) View Slides Here
  5. Benefit/risk assessment in SPAF – integrating stroke prevention and bleeding in a non-inferiority study – (Academic
    perspective) – Mike Gibson (BCRI) View Slides Here
  6. Considerations in designing benefit-risk analyses involving outcome importance weighting or ranking (FDA
    perspective) – Leila Lackey (FDA) View Slides Here

BREAK
Panel Discussion: PANELISTS – Norman Stockbridge (moderator); Dan Bloomfield (moderator); Roxana Mehran; Leslie
Lake; Shelby Reed; Bennett Levitan; Mike Gibson; Elliot Barnathan; Leila Lackey

BREAK/LUNCH

Session 4:  Management of bleeding, procedures, and urgent surgery 
Moderators: Ricardo Garcia-Sanchez (BMS), Jordan Pomeroy (FDA)
  1. Experience from patients with Factor XI deficiency – Jean Connors (BWH) View Slides Here
  2. Urgent bleeding management strategies – Jeff Weitz (McMaster) View Slides Here
  3. Experience with managing urgent surgery with a long-acting FXI inhibitor – Christian Ruff (TIMI) View Slides Here
  4. Regulatory Perspective – what data are needed? – Jordan Pomeroy (FDA) View Slides Here
  5. Panel Discussion: PANELISTS – Ricardo Garcia-Sanchez (moderator); Jordan Pomeroy (moderator); Jean Connors; Christian Ruff; Jeff Weitz; Jordan Pomeroy; Dan Bloomfield 
Meeting Summary – Session Moderators and Q&A