Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301)

Summary

This Phase III clinical study will assess the impact of BMN 270 (compared to FVIII prophylaxis) on the number of bleeding episodes irrespective of exogenous FVIII replacement treatment in the efficacy evaluation period (EEP) (from Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). The study will also assess the impact of BMN 270 (compared to FVIII prophylaxis) on: the number of bleeding episodes requiring exogenous FVIII treatment in "Post FVIII Prophylaxis to Last Visit", FVIII activity as measured by chromogenic sustrate assay at Week 104 following intravenous infusion of BMN 270, usage of exogenous FVIII replacement therapy in "Post FVIII Prophylaxis to Last Visit", health-related quality of life patient-reported outcomes at week 104 following intravenous infusion of BMN 270. The study will also evaluate the safety of the BMN 270.

Timeline

Start

2017-12-19

Primary completion

2020-11-16

Completion

2024-11-20

Outcome

Met primary endpoint

registry analysis (superiority test); BMN 270 (Valoctocogene Roxaparvovec); p <0.0001; % Reduction from Baseline -77.0; t-test, 2 sided NCT03370913 ↗

release “the pre-specified primary analysis for Annualized Bleeding Rate (ABR) a single dose of valoctocogene roxaparvovec significantly reduced ABR by 84%” biomarin.com ↗

release “The pivotal study demonstrated superiority to Factor VIII prophylaxis in key clinical efficacy endpoints.” biomarin.com ↗

release “The two-year data from the 134-participant Phase 3 study, shared in January 2022 , met all primary and secondary efficacy endpoints.” biomarin.com ↗

release “The GENEr8-1 Phase 3 study demonstrated stable and durable bleed control, including a reduction in the mean annualized bleeding rate (ABR)” biomarin.com ↗

Publications

• Santos S, Robinson TM, Trueman D. Estimated Long-Term Durability of Valoctocogene Roxaparvovec Treatment in Male patients with Severe Hemophilia A: An Extrapolation of Clinical Data. Adv Ther. 2025 Nov;42(11):5781-5793. doi: 10.1007/s12325-025-03368-4. Epub 2025 Sep 23.
• Agarwal S, Sandza K, Obrochta Moss K, Vora M, Bowen A, Bunch B, Holcomb J, Robinson TM, Jayaram K, Russell CB, Zoog S, Vettermann C, Henshaw J. Blood biodistribution and vector shedding of valoctocogene roxaparvovec in people with severe hemophilia A. Blood Adv. 2024 Sep 10;8(17):4606-4615. doi: 10.1182/bloodadvances.2024013150.
• Oldenburg J, Chambost H, Liu H, Hawes C, You X, Yang X, Newman V, Robinson TM, Hatswell AJ, Hinds D, Santos S, Ozelo M. Comparative Effectiveness of Valoctocogene Roxaparvovec and Prophylactic Factor VIII Replacement in Severe Hemophilia A. Adv Ther. 2024 Jun;41(6):2267-2281. doi: 10.1007/s12325-024-02834-9. Epub 2024 Apr 15.
• Mahlangu J, Kaczmarek R, von Drygalski A, Shapiro S, Chou SC, Ozelo MC, Kenet G, Peyvandi F, Wang M, Madan B, Key NS, Laffan M, Dunn AL, Mason J, Quon DV, Symington E, Leavitt AD, Oldenburg J, Chambost H, Reding MT, Jayaram K, Yu H, Mahajan R, Chavele KM, Reddy DB, Henshaw J, Robinson TM, Wong WY, Pipe SW; GENEr8-1 Trial Group. Two-Year Outcomes of Valoctocogene Roxaparvovec Therapy for Hemophilia A. N Engl J Med. 2023 Feb 23;388(8):694-705. doi: 10.1056/NEJMoa2211075.
• Quinn J, Delaney KA, Wong WY, Miesbach W, Bullinger M. Psychometric Validation of the Haemo-QOL-A in Participants with Hemophilia A Treated with Gene Therapy. Patient Relat Outcome Meas. 2022 Jul 18;13:169-180. doi: 10.2147/PROM.S357555. eCollection 2022.
• Ozelo MC, Mahlangu J, Pasi KJ, Giermasz A, Leavitt AD, Laffan M, Symington E, Quon DV, Wang JD, Peerlinck K, Pipe SW, Madan B, Key NS, Pierce GF, O'Mahony B, Kaczmarek R, Henshaw J, Lawal A, Jayaram K, Huang M, Yang X, Wong WY, Kim B; GENEr8-1 Trial Group. Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A. N Engl J Med. 2022 Mar 17;386(11):1013-1025. doi: 10.1056/NEJMoa2113708.
• Rosen S, Tiefenbacher S, Robinson M, Huang M, Srimani J, Mackenzie D, Christianson T, Pasi KJ, Rangarajan S, Symington E, Giermasz A, Pierce GF, Kim B, Zoog SJ, Vettermann C. Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy. Blood. 2020 Nov 26;136(22):2524-2534. doi: 10.1182/blood.2020005683.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	valoctocogene roxaparvovec	Gene therapy (AAV / viral vector)	6e+13 vg/kg	Intravenous

Indications