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General Information
Roctavian (valoctocogene roxaparvovec-rvox) is an adeno-associated virus vector-based gene therapy.
Roctavian is specifically indicated for the treatment of adults with severe hemophilia A (congenital factor VIII deficiency with factor VIII activity < 1 IU/dL) without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test.
Roctavian is supplied as a one-time single-dose intravenous infusion,
- Perform baseline testing to select patients, including testing for pre-existing antibodies to adeno-associated virus serotype 5 (AAV5), factor VIII inhibitor presence, and liver health assessments.
- The recommended dose of Roctavian is 6 × 1013 vector genomes (vg) per kg of body weight.
- Start the infusion at 1 mL/min. If tolerated, the rate may be increased every 30 minutes by 1 mL/min up to a maximum rate of 4 mL/min.
Mechanism of Action
Roctavian (valoctocogene roxaparvovec-rvox) is an adeno-associated virus serotype 5 (AAV5) based gene therapy vector, designed to introduce a functional copy of a transgene encoding the B-domain deleted SQ form of human coagulation factor VIII (hFVIII-SQ). Transcription of this transgene occurs within the liver, using a liver-specific promoter, which results in the expression of hFVIII-SQ. The expressed hFVIII-SQ replaces the missing coagulation factor VIII needed for effective hemostasis.
Side Effects
Side effects associated with the use of Roctavian may include, but are not limited to, the following:
- nausea
- fatigue
- headache
- infusion-related reactions
- vomiting
- abdominal pain
Most common laboratory abnormalities (incidence ≥ 10%) include:
- alanine aminotransferase (ALT)
- aspartate aminotransferase (AST)
- lactate dehydrogenase (LDH)
- creatine phosphokinase (CPK)
- factor VIII activity levels
- gamma-glutamyl transferase (GGT)
- bilirubin > ULN
Clinical Trial Results
FDA approval was based on data from the global Phase 3 GENEr8-1 study. Of the 134 patients who received Roctavian in the study, 112 patients had baseline annualized bleeding rate (ABR) data prospectively collected during a period of at least six months on FVIII prophylaxis prior to receiving Roctavia. The remaining 22 patients had baseline ABR collected retrospectively. All patients were followed for at least 3 years.
The 112 patients in whom 6-month baseline ABR was collected prospectively experienced a mean ABR reduction of 52% after receiving Roctavian (2.6 bleeds/year) through end of follow-up (median of three years) compared to their baseline ABR while receiving routine FVIII prophylaxis (5.4 bleeds/year). This result was based on an FDA analysis that imputed an ABR of 35 in 13 patients for the periods when these patients were on prophylaxis. These patients also reported a substantial reduction in the rate of spontaneous bleeds and joint bleeds following treatment with Roctavian (observed mean ABR of 0.5 bleeds/year for spontaneous bleeds and 0.6 bleeds/year for joint bleeds) compared to their baseline rate while receiving routine FVIII prophylaxis (observed mean ABR of 2.3 bleeds/year for spontaneous bleeds and 3.1 bleeds/year for joint bleeds).
The majority of study participants continued to respond to treatment through year three and beyond, without supplemental use of regular prophylaxis.