Valoctocogene Roxaparvovec-rvox

1 INDICATIONS AND USAGE ROCTAVIAN is an adeno-associated virus vector-based gene therapy indicated for the treatment of adults with severe hemophilia A (congenital factor VIII deficiency with factor VIII activity < 1 IU/dL) without antibodies to adeno-associated virus serotype 5 (AAV5) detected by an FDA-approved test. ROCTAVIAN is an adeno-associated virus vector-based gene therapy 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. ( 1 )

6 ADVERSE REACTIONS The following adverse reactions are also discussed in other sections of the label: Infusion-Related Reactions [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥ 5%) were nausea, fatigue, headache, infusion-related reactions, vomiting, and abdominal pain. ( 6 ) Most common laboratory abnormalities (incidence ≥ 10%) were ALT, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), factor VIII activity levels, gamma-glutamyl transferase (GGT) and bilirubin > ULN. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-866-906-6100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary ROCTAVIAN is not intended for administration in women. There are no data on the use of ROCTAVIAN in pregnant women to inform a drug-associated risk of adverse developmental outcome. Animal reproduction and developmental toxicity studies have not been conducted with ROCTAVIAN. It is not known whether ROCTAVIAN can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

5 WARNINGS AND PRECAUTIONS Infusion-related reactions: Infusion reactions, including hypersensitivity reactions and anaphylaxis, have occurred. Monitor during and for at least 3 hours after ROCTAVIAN administration. If symptoms occur, slow or interrupt administration and give appropriate treatment. Restart infusion at slower rate once symptoms resolve. Discontinue infusion for anaphylaxis. ( 2.3 , 5.1 ) Hepatotoxicity: Monitor alanine aminotransferase (ALT) weekly for at least 26 weeks and institute corticosteroid treatment in response to ALT elevations as required. Continue to monitor ALT until it returns to baseline. Monitor factor VIII activity levels since ALT elevation may be accompanied by a decrease in factor VIII activity. 4 CONTRAINDICATIONS Administration of ROCTAVIAN is contraindicated in: patients with active infections, either acute (such as acute respiratory infections or acute hepatitis) or uncontrolled chronic (such as chronic active hepatitis B) . patients with known significant hepatic fibrosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent), or cirrhosis [see Dosage and Administration (2) ].