PRACTICE AID EHL FVIII Regimens for the Management of Hemophilia A

Current and Emerging Extended Half-Life Factor VIII Therapies

Approved for Hemophilia A Investigational   Rurioctocog alfa pegol BIVV001  pegol

FDA-Approved Extended Half-Life Products for Hemophilia A1-5

Damoctocog Efmoroctocog Rurioctocog Turoctocog Alfa Pegol Alfa Alfa Pegol Alfa Pegol

2018 Adults and 2014 2015 2019 FDA Approval adolescents, Adults and children Adults and children Adults and children previously treated

rFVIII Design B-domain deleted B-domain deleted Full length B-domain truncated

Modification to PEG PEG PEG Fc fusion EHL (60 kDa) (20 kDa) (40 kDa)

Half-Life, h (adult) 19 19 14.3 - 16 19

30-40 units/kg 50 units/kg 2x/week every 4 days 50 units/kg

every 4 days Adjust: 45-60 units/kg 40-50 units/kg Adjust: less or more Dosing (adult) every 5 days; 2x/week frequent dosing Adjust: 25-65 units/kg may be further based on bleeding every 3-5 days adjusted to less or episodes more frequent dosing

• All are highly effective when used as prophylaxis with ABRs significantly Efficacy improved compared to no prophylaxis • Also effective for breakthrough bleeds and perioperative management

Safety • Generally well tolerated with no unexpected safety issues

Access the activity, “Implementing Care With Extended Half-Life Factor VIII Therapy in Hemophilia A: An Interdisciplinary Conversation on Personalized Patient Management,” at PeerView.com/CEV40 PRACTICE AID EHL FVIII Regimens for the Management of Hemophilia A

Extended Half-Life Replacement Factors for Hemophilia A1-5

Top-Line Summary of Selected Half-Life Extension MOA Clinical Data on EHL

Fc Fusion ABR ↓ vs On-Demand Protein of interest Fc region A-LONG Study Individualized prophylaxis Name: Efmoroctocog alfa PEG Protein of interest in vivo t1/2: 19 h PEG

o H H o 92%n Fc region PEG

ABR ↓ vs On-Demand PEGylation PROTECT VIII Study 1x/5 d prophylaxis Name: Damoctocog alfa pegol

in vivo t1/2: 19 h Protein of interest Fc region 96% PEG Protein of interest PEG PROLONG-ATE Study Twice weekly prophylaxis

o H Name: Rurioctocog alfa pegol H o n in vivo t1/2: 14.3 - 16 h Fc region PEG 90%

PathfinderTM1 Study 1x/4 d prophylaxis Name: Turoctocog alfa pegol in vivo t : 19 h 1/2 96%

1 patient developed FVIII inhibitors after 93 exposure days

ABR: annualized bleeding rate; EHL: extended half-life; FVIII: factor VIII; MOA: mechanism of action; PEG: polyethylene glycol; rFVIII: recombinant factor VIII; t1/2: half-life. 1. Konkle BA et al. . 2015;126:1078-1085. 2. Mahlangu J et al. Blood. 2014;123:317-325. 3. Coyle TE et al. J Thromb Haemost. 2014;12:488-496. 4. Tiede A et al. J Thromb Haemost. 2013;11:670-678. 5. Iorio A. Hematology Am Soc Hematol Educ Program. 2017;2017:595-604. Access the activity, “Implementing Care With Extended Half-Life Factor VIII Therapy in Hemophilia A: An Interdisciplinary Conversation on Personalized Patient Management,” at PeerView.com/CEV40 PRACTICE AID Shared Decision-Making in Hemophilia A1

Step 5 Evaluate patient’s interaction Promote decision between patient and Step 4 Goals of Shared Decision-Making the patient to healthcare professional Activate Reach decision increase the role they assume with patient in illness management Inform the patient to improve their knowledge Step 3 about their own illness Assess patient’s values and preferences Step 2 Help patient explore, compare treatment options Step 1 Seek patient’s participation

Communicate that a choice Take into account what Decide together on the exists and invite your patient Discuss the benefits matters most to your best option and arrange Revisit decision, to be involved in decisions and risks of each option patient follow-up appointment monitor implementation

Benefits to Healthcare Professionals Benefits to Patients • Improved quality of care delivered • Improved patient experience of care • Increased patient satisfaction • Improved patient adherence to treatment recommendations

1. https://www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/tools/index.html. Access the activity, “Implementing Care With Extended Half-Life Factor VIII Therapy in Hemophilia A: An Interdisciplinary Conversation on Personalized Patient Management,” at PeerView.com/CEV40 PRACTICE AID Individualization of Care in Hemophilia A: Factors to Consider1,2

Is an EHL FVIII Regimen the Right Choice for Your Patient? Variables that affect decision-making Patient-Specific Factors Treatment-Related Factors

Age

Timing of infusions

Bleeding phenotype

Physical activity Pharmacokinetics • Type • in vivo rFVIII half-life • Pattern • FVIII peak/trough

Joint status

Product used

Adherence

Venous access

A Single, Severity-Based, Therapeutic Model Does Not Represent Advantages of Personalizing Therapy the Optimal Treatment Strategy for All Patients With Hemophilia A  Reduction of factor administration • Individualization of hemophilia care is recommended  Financial impact to health system • Underscores the need for shared decision-making  More accurate assessment of patient-specific FVIII concentrations over time  Maximize efficacy

EHL: extended half-life; FVIII: factor VIII; rFVIII: recombinant factor VIII. 1. Iorio A. Hematology Am Soc Hematol Educ Program. 2017;2017:595-604. 2. Hazendonk HCAM et al; OPTI-CLOT study group. Blood Rev. 2018;32:265-271. Access the activity, “Implementing Care With Extended Half-Life Factor VIII Therapy in Hemophilia A: An Interdisciplinary Conversation on Personalized Patient Management,” at PeerView.com/CEV40