Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients

Inclusion Criteria:

- Males ≥ 18 years of age with hemophilia A and residual FVIII levels ≤ 1 IU/dL as
evidenced by medical history, at the time of signing the informed consent.

- Must have been on prophylactic FVIII replacement therapy for at least 12 months prior
to study entry. High-quality, well-documented historical data concerning bleeding
episodes and FVIII usage over the previous 12 months must be available.

- Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure
days (EDs).

- No previous documented history of a detectable FVIII inhibitor, and results from a
Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda
Units (BU) (or less than 1.0 BU for laboratories with a historical lower sensitivity
cutoff for inhibitor detection of 1.0 BU) on 2 consecutive occasions at least one week
apart within the past 12 months (at least one of which should be tested at the central
laboratory).

Exclusion Criteria:

- Detectable pre-existing antibodies to the AAV5 capsid.

- Any evidence of active infection or any immunosuppressive disorder, including HIV
infection.

- Significant liver dysfunction with any of the following abnormal laboratory results:

- ALT (alanine aminotransferase) > 1.25x ULN;

- AST (aspartate aminotransferase) > 1.25x ULN;

- GGT (gamma-glutamyltransferase) > 1.25x ULN;

- Total bilirubin > 1.25x ULN;

- Alkaline phosphatase > 1.25x ULN

- INR (international normalized ratio) ≥ 1.4.

Subjects whose liver laboratory assessments fall outside of these ranges may undergo repeat
testing of the entire liver test panel within the same Screening window and, if eligibility
criteria are met on retest, may be enrolled after confirmation by the Medical Monitor.

- Prior liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0-4
on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or an
equivalent grade of fibrosis if an alternative scale is used.

- Evidence of any bleeding disorder not related to hemophilia A.

- Platelet count of < 100 x 10^9/L.

- Creatinine ≥ 1.5 mg/dL.

- Liver cirrhosis of any etiology as assessed by liver ultrasound.

- Chronic or active hepatitis B as evidenced by positive serology testing (hepatitis B
surface antigen [HBsAg], hepatitis B surface antibody [HBsAb], and hepatitis B core
antibody [HBcAb]) and confirmatory HBV DNA testing. Refer to the Centers for Disease
Control (CDC) table for the interpretation of serological test results.

- Active Hepatitis C as evidenced by detectable HCV RNA or currently on antiviral
therapy.

- Active malignancy, except non-melanoma skin cancer.

- History of hepatic malignancy.

- History of arterial or venous thromboembolic events (eg, deep vein thrombosis,
nonhemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolus),
with the exception of catheter-associated thrombosis for which anti-thrombotic
treatment is not currently ongoing.

- Known inherited or acquired thrombophilia, including conditions associated with
increased thromboembolic risk, such as atrial fibrillation.