Rebalancing agents represent a new class of therapies with specific safety monitoring requirements, particularly around thrombotic risk. As with gene therapy patients, the Patient Timeline (Section 3) allows centres to review the full monitoring history for each patient and identify missing assessments or laboratory results. The protocols below define the data collection schedule for CBDR.
This section covers monitoring for concizumab, fitusiran, and marstacimab as rebalancing agents for Hemophilia A or B with or without inhibitors (CDA DRD priority level 3).
Evidence Gaps Being Addressed
- Limited real-world effectiveness data compared to traditional therapies
- Insufficient long-term safety data, particularly thrombotic risk
- Uncertainty regarding patient selection and treatment sequencing
- Limited comparative patient-reported outcome data
- Inadequate data on optimal dosing strategies
Product-Specific Information
Agent | Mechanism | Indication | Approval Status |
Concizumab | Anti-TFPI monoclonal antibody | Hem A/B with or without inhibitors | FDA approved Dec 2024 |
Fitusiran | siRNA targeting antithrombin | Hem A/B with or without inhibitors | FDA approved Mar 2025 |
Marstacimab | Anti-TFPI monoclonal antibody | Hem A/B without inhibitors | FDA approved Oct 2024 |
Baseline Data Collection
Complete prior to initiating rebalancing agent:
Category | Required Data |
Patient Demographics | Age, weight, diagnosis (Hem A or B), severity, inhibitor status (current and historical) |
Prior Treatment History | Previous prophylaxis regimens, products used, reasons for switching, history of ITI if applicable |
Bleeding History | 12-month ABR (total and joint bleeds), target joints, spontaneous vs. traumatic bleeds |
Thrombotic Risk Assessment | History of thrombosis, cardiovascular disease, use of hormonal therapy, immobility risk factors |
Laboratory Baseline | Factor level, inhibitor titer, D-dimer, fibrinogen, platelet count, liver/renal function |
Joint Health | HJHS total and individual joint scores |
Quality of Life | PROBE score, EQ-5D, pain VAS |
Ongoing Monitoring Schedule
Timepoint | Assessments | Focus |
Week 1-4 | Bleeding episodes, injection site reactions | Early safety monitoring |
Monthly (M1-6) | Bleed count, adverse events, adherence | Efficacy signal |
Month 3 | PROBE, pain VAS, bleed rate calculation | Early PRO and efficacy |
Month 6 | HJHS, PROBE, EQ-5D, 6-month ABR, laboratory panel | Comprehensive 6-month review |
Month 12 | Full assessment: HJHS, PROBE, EQ-5D, 12-month ABR, factor consumption, lab panel | Annual efficacy, comparative data |
Ongoing | All bleeds, adverse events, treatment for bleeds (bypass agents) | Real-time safety and efficacy |
Critical Safety Monitoring
Report immediately. Thrombotic events are a class concern:
- Venous thromboembolism (DVT, PE)
- Arterial thrombosis (stroke, MI, peripheral arterial)
- Catheter-related thrombosis
- Thrombotic microangiopathy
Also report:
- Injection site reactions (severity, duration)
- Hypersensitivity reactions
- Breakthrough bleeds requiring bypass agent use
- Any hospitalization