P135 Efficacy and safety of 144 weeks of bulevirtide 2 mg or 10 mg monotherapy from the ongoing phase 3 study, MYR301

<h3></h3> Bulevirtide (BLV) is approved in Europe for treatment of chronic hepatitis delta (CHD). In a Phase 3 study over 96 weeks (W), BLV 2 mg or 10 mg monotherapy was effective and safe. Here, we present W144 results. 150 patients with CHD were randomised: arm A (delayed treatment): observed for 48 weeks followed by BLV 10 mg/d for 96 weeks (n=51); arm B: BLV 2 mg/d for 144 weeks (n=49); arm C: BLV 10 mg/d for 144 weeks (n=50). W144 efficacy endpoints included virologic response (VR; undetectable HDV RNA or ≥2 log₁₀ IU/mL decline from baseline [BL]), alanine aminotransferase (ALT) normalisation, combined response (CR; VR and ALT normalisation), and undetectable HDV RNA (target not detected). Univariate logistic regression was used to discern if any BL characteristics predicted undetectable HDV RNA at W144 for patients in arms B and C who completed W144 and had BL HDV RNA ≥250 log₁₀ IU/mL. Predictors with P&lt;.05 were significant. At W144, 96% (49/51), 92% (45/49), and 88% (44/50) in arms A, B, and C remained in study. Arms B and C had similar rates of CR, VR, and ALT normalisation; rates increased through W96 and were maintained through W144 (figure 1). Undetectable HDV RNA rates increased with BLV treatment and were 29% in arm B and 50% in arm C at W144. BL predictors of W144 undetectable HDV RNA were lower HDV RNA (BLV 2 mg: odds ratio [OR] 2.9, P=.0145; BLV 10 mg: OR 2.1, P=.0258) and lower hepatitis B surface antigen (HBsAg) (BLV 2 mg: OR 5.1, P=.0319; BLV 10 mg: OR 6.0, P=.0390). W144 HBsAg mean (SD) change from BL was −0.36 (0.596) and −0.19 (0.39) log₁₀ IU/mL with BLV 2 mg and BLV 10 mg. At W144 in arm A (96 weeks of BLV), rates of CR, VR, ALT normalisation, and undetectable HDV RNA were 56%, 92%, 58%, and 52%. There was no progression to liver-related outcomes over 144 weeks except for 1 case of mild ascites in arm A (patient with BL cirrhosis). Through W144 of BLV therapy, there were no drug discontinuations, serious adverse events, or deaths attributed to BLV; the safety profile was similar for both doses. Dose-dependent increases in bile acids remained asymptomatic. Improvements in biochemical, fibrosis, and virologic markers, including increased rates of undetectable HDV RNA, and low occurrence of liver-related events support the potential clinical benefits of long-term BLV therapy over 144 weeks.