There are no reports of valoctocogene roxaparvovec accidental infusions or high dose volumes. If considered necessary, the treatment of a valoctocogene roxaparvovec overdose should be symptomatic and supportive. Receiving higher doses than recommended may result in higher factor VIII activity levels, associated with an increased risk of thrombotic events.^L43282

At doses up to 2×10¹⁴ vg/kg, CD1 mice given valoctocogene roxaparvovec did not show any signs of toxicity, except for a pattern of hemorrhages, necrosis and fibrosis in the heart, lungs, epididymis and thymus. These effects were consistent with a coagulopathy likely caused by the formation of SQ form of human coagulation factor VIII (hFVIII-SQ) antibodies that cross-reacted with the murine factor VIII protein.^L43282 Vector integration was detected in the liver samples of non-human primates (n=12), which may lead to a higher risk of malignancies. Reproductive and developmental toxicity studies have not been performed. Since the majority of the patient population are males, germline transmission was evaluated in pups sired by male mice dosed with valoctocogene roxaparvovec. No germline transmission was detected.^L43282