Phase III GENEr8-1 study safety update of Roctavian in haemophilia A.- BioMarin Pharma

In the GENEr8-1 Phase III study, Annualized Bleeding Rate (ABR) was significantly reduced by 4.1 treated bleeds per year (p-value <0.0001), or by 85% from a baseline mean of 4.8 (median 2.8), in the pre-specified primary analysis in participants from a prior non-interventional study (rollover population; n="112;" median follow-up of 110 weeks). the percentage of participants with zero treated bleeds increased from 32% on prophylaxis at baseline to 82% during year 1 and 84% during year 2. the mean abr was 0.8 (median 0.0) through the entire efficacy evaluation period, 0.9 (median 0.0) during year one, and 0.7 (median 0.0) during year two. across all participants in the rollover population (n="112)," mean annualized factor viii infusion rate was reduced by 133 infusions per year (p-value><0.0001) or 98% from baseline. as of the two-year data cut, 95% of participants remain off factor viii prophylactic therapy.></0.0001)></0.0001),>

All participants in the Phase III study received a single 6e13 vg/kg dose. No participants developed inhibitors to Factor VIII, malignancy, or thromboembolic events. During year two, no new safety signals emerged, and no treatment-related serious adverse events (SAE) were reported. Most patients had discontinued any corticosteroid (CS) use in year one, and there were no CS-related SAEs in the remaining patients being tapered off CS in year two. Overall, the most common adverse events (AE) associated with valoctocogene roxaparvovec occurred early and included transient infusion associated reactions and mild to moderate rise in liver enzymes with no long-lasting clinical sequelae. Alanine aminotransferase (ALT) elevation (119 participants, 89%), a laboratory test of liver function, remained the most common AE. Other common adverse events were headache (55 participants, 41%), arthralgia (53 participants, 40%), nausea (51 participants, 38%), aspartate aminotransferase (AST) elevation (47 participants, 35%), and fatigue (40 participants, 30%).

In a Phase I/II study, an SAE of a salivary gland mass was identified in one study participant, who was treated more than five years ago, and was reported as unrelated to valoctocogene roxaparvovec by the investigator. The relevant health authorities were notified in late 2021, and all studies remain ongoing without modification. The independent Data Monitoring Committee (DMC) further reviewed the case. A genomic analysis is being conducted as prespecified in the clinical trial protocol. Data were presented at the 15th Annual Virtual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD).