BioMarin received approval from the U.S. Food and Drug Administration (FDA) on June 29, 2023, for Roctavian^™ (valoctocogene roxaparvovec-rvox), an adeno-associated virus vector (AAV)-based gene therapy. It is indicated for the treatment of adults who have severe hemophilia A (congenital factor VIII deficiency) with factor VIII activity less than 1 IU/dL without pre-existing antibodies to AAV serotype 5 (AAV5) as detected by an FDA-approved test. Hemophilia A is caused by mutations in the gene that express coagulation protein factor VIII, a factor responsible for blood clotting. The AAV vector can penetrate cells without harming them and replace the non-functioning gene needed to produce factor VIII. Individuals who have hemophilia A are at risk for severe, life-threatening bleeding from common injuries and painful spontaneous bleeding into the joints and muscles. In the U.S., hemophilia A affects around one in 10,000 individuals, almost entirely males. Since candidates for Roctavian therapy also need to test negative for AAV5 antibodies, BioMarin estimates that about 2,500 people may be eligible to receive it. The recommended dose is 6 × 10¹³ vector genomes per kilogram (vg/kg) body weight, administered as a single intravenous (IV) infusion. The wholesale acquisition cost (WAC) is $2.9 million. It will be available in a limited small network and Accredo will have access. A link to the complete prescribing information is not yet available; however, it should be available soon on the company’s website.

At a Glance

• Brand (Generic) Name: Roctavian (valoctocogene roxaparvovec-rvox)
• Manufacturer: BioMarin
• Date Approved: June 29, 2023
• Indication: For the treatment of adults who have severe hemophilia A (congenital factor VIII (FVIII) deficiency with FVIII activity less than 1 IU/dL without antibodies to AAV5 as detected by an FDA-approved test
• Dosage Forms Available: Suspension for infusion containing 2 × 10¹³ vg per mL. Each carton contains one single-dose vial containing an extractable volume of not less than 8 mL, for a total of 16 × 10¹³ vg.
• Launch Date: Within the next 8 weeks
• Estimated Annual Cost: Wholesale acquisition cost of $2.9 million for a one-time, single-dose treatment
• Approximately four-fifths of patients who have hemophilia, or about 16,000 U.S. citizens, predominantly boys, and men, have the A-type. A mainly inherited condition, hemophilia A tends to be more severe than other types. Between 50% and 60% of patients who have it have the severe form of the condition, which means that they produce 2% or less of normal factor VIII levels.
• Up to 35% of patients who have hemophilia A develop inhibitors, antibodies that reduce the effectiveness of factor VIII replacement.
• The current treatment for hemophilia A is recombinant factor VIII products that treat and prevent bleeding episodes. Most are administered by IV infusion, usually two times to four times a week to prevent bleeds.
• Genentech’s Hemlibra^® (emicizumab-kxwh) has been marketed in the U.S. since November 2017, for routine use to prevent or reduce the frequency of bleeding episodes for adult and pediatric patients who have hemophilia A. Additionally, Sanofi’s Altuviiio™ [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl]), was approved by the FDA on Feb. 22, 2023, for both preventing and treating bleeding episodes in patients with hemophilia A.
• In its phase III pivotal trial, (GENEr8-1), Roctavian was administered to 134 adult males who have hemophilia A and who previously were treated with prophylactic factor VIII replacement therapy. Overall, the 112 men who had six months of records from before their Roctavian treatments averaged a 52% reduction in annual bleeding rates (ABR), with an average of 5.2 bleeds per year reduced to an average of 2.6 bleeds per year.
• Patients treated with Roctavian also saw factor VIII usage reduced by 96.8% per year at a median follow-up of approximately three years. All patients are enrolled in 15-year-long extension studies to evaluate the long-term safety and efficacy of the therapy.
• Its label warns that Roctavian can cause infusion-related reactions, anaphylaxis, liver toxicity, thromboembolic events, and increased risk for liver cancer. The most common side effects were nausea, fatigue, headache, infusion-related reactions, vomiting, and abdominal pain.
• BioMarin announced an outcomes-based warranty program for government and commercial payers. The warranty will reimburse at least part of the cost of Roctavian if therapy fails within the first four years following treatment.
• Roctavian was designated as a Breakthrough Therapy and given Priority Review. It is also an Orphan Drug for hemophilia A. Additionally, it qualified for regenerative medicine therapy (RMAT) status, which is granted to cell therapies and similar products intended to manage serious or life-threatening conditions.

Embarc Benefit Protection Strategy: Evernorth is reviewing the clinical efficacy and safety information in addition to the financial impact of BioMarin’s newly approved gene therapy, Roctavian, and further evaluation is needed. As such, Evernorth has not yet made a determination if Roctavian will be added to Embarc Benefit Protection. The Embarc team will provide confirmation as soon as possible.