Study to Evaluate the Efficacy and Safety of Valoctocogene Roxaparvovec, With Prophylactic Steroids in Hemophilia A

Inclusion Criteria: 1. 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. 2. Must have been on prophylactic hemophilia therapy for at least 12 months prior to study entry. High-quality, well-documented historical data concerning bleeding episodes and hemophilia therapy usage over the previous 12 months must be available. 3. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs). 4. Willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any study-related procedures. 5. 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). 6. Sexually active participants must agree to use an acceptable method of effective contraception, either double-barrier contraception (ie, condom + diaphragm; or condom or diaphragm + spermicidal gel or foam) or their female partner either using hormonal contraceptives or having an intrauterine device. Participants must agree to contraception use for at least 12 weeks post-infusion; after 12 weeks, participants may stop contraception use only if they have had 3 consecutive semen samples with viral vector DNA below the limit of detection. 7. Willing to abstain from alcohol consumption for at least the first 52 weeks following BMN 270 infusion. Exclusion Criteria: 1. Participants with detectable pre-existing antibodies to the adeno-associated virus (AAV5) capsid are excluded with the following exception: up to 25% of participants may have detectable pre-existing AAV5 capsid antibodies with titer level below the minimum required dilution (\< 20). 2. Any evidence of active infection, including Coronavirus Disease (COVID-19), or any immunosuppressive disorder, except for HIV infection. HIV-positive patients who meet all other eligibility criteria may be included if they have a CD4 count \> 200/mm\^3 and an undetectable viral load (unquantifiable viral load as defined as less than the limit of quantification by the testing laboratory's assay is permitted) while receiving an antiretroviral therapy (ART) regimen that does not contain efavirenz or another potentially hepatotoxic ART. 3. Significant liver dysfunction with any of the following abnormal laboratory results: alanine aminotransferase (ALT) \> 1.25x upper limit of normal (ULN);aspartate aminotransferase (AST) \> 1.25x ULN;gamma-glutamyltransferase (GGT) \> 1.25x ULN;Total bilirubin \> 1.25x ULN;Alkaline phosphatase \> 1.25x ULN; or international normalized ratio (INR) \>= 1.4. Participants whose liver laboratory assessments fall outside of these ranges could undergo repeat testing of the entire liver test panel within the same Screening window and, if eligibility criteria are met on retest, could be enrolled after confirmation by the Medical Monitor. 4. FibroScan or 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. 5. Evidence of any bleeding disorder not related to hemophilia A. 6. Platelet count of \< 100 x 10\^9/L. 7. Creatinine \>= 1.5 mg/dL 8. Liver cirrhosis or other clinically significant liver disease of any etiology as assessed by FibroScan or liver ultrasound. 9. 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 hepatitis B virus (HBV) DNA testing. Refer to the Centers for Disease Control (CDC) table for the interpretation of serological test results in the Laboratory Manual. 10. Active Hepatitis C as evidenced by detectable hepatitis C virus (HCV) RNA or currently on antiviral therapy. 11. Active malignancy, except non-melanoma skin cancer. 12. History of hepatic malignancy. 13. History of arterial or venous thromboembolic events (eg, deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolus), with the exception of catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing. 14. Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation. 15. Treatment with any investigational product within 30 days or 5 half-lives of the investigational product prior to the screening period. For participants who have received a prior investigational product, all ongoing adverse events (AEs) experienced while receiving that investigational product must have resolved prior to screening for this study. 16. Any condition that, in the opinion of the Investigator or Sponsor would prevent the patient from fully complying with the requirements of the study (including possible corticosteroids (CS) treatment and/or use of alternative immunosuppressive agents (AIS) outlined in the protocol) and/or would impact or interfere with evaluation and interpretation of participant safety or efficacy result. 17. Prior treatment with any vector or gene transfer agent. 18. Major surgery planned in the 52-week period following the infusion with BMN 270. 19. Use of systemic immunosuppressive agents, not including CS, or live vaccines within 30 days before the BMN 270 infusion. 20. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study that does not interfere with the requirements of the current protocol or have the potential to impact the evaluation of efficacy and safety of BMN 270 and with prior consultation with the Medical Monitor. 21. Known allergy or hypersensitivity to BMN 270 investigational product formulation. 22. Unwilling to receive blood or blood products for treatment of an adverse event and/or a bleeding episode. Optional Liver Biopsy Inclusion and Exclusion Criteria Individuals eligible for the optional liver biopsy must meet the following inclusion criteria: 1. Able to sign informed consent and comply with requirements for the optional liver biopsy 2. Documentation of FVIII activity \>= 50 IU/dL (or higher, depending on local guidelines and/or Investigator discretion) within 24 hours prior to the liver biopsy being performed (FVIII activity levels should be assessed at the local laboratory). Participants may be treated with additional exogenous FVIII replacement products in order to increase their FVIII activity to an appropriate level, under the supervision/instruction of the Investigator. Individuals who meet the following exclusion criterion are not be eligible for the optional liver biopsy: 1\. Any condition that, in the opinion of the Investigator or a hepatologist/radiologist would make liver biopsy contraindicated. This includes (but is not limited to) abnormalities detected on liver ultrasound performed within 28 days of procedure, or prior liver ultrasound result within 90 days that would preclude safe performance of the biopsy