P134 Efficacy and safety of 48-week off-therapy of Bulevirtide in combination with pegylated interferon alfa-2a in patients with chronic hepatitis delta: final results from the phase 2b, open-label, randomised, multicentre study MYR204

<h3></h3> Bulevirtide (BLV) is approved in Europe for treatment of chronic hepatitis delta (CHD). This Phase 2b study evaluated the safety and efficacy of BLV (2 mg and 10 mg) with/without pegylated interferon alfa-2a (PegIFN) in patients with compensated CHD. Here we present the results at 48 weeks (W) post-end of treatment (EOT). 174 patients with CHD were randomised (1:2:2:2) and stratified based on the absence/presence of compensated cirrhosis to receive (A) PegIFN for 48W, (B) BLV 2 mg + PegIFN, (C) BLV 10 mg + PegIFN for 48W followed by 48W of monotherapy with BLV 2 mg or 10 mg, or (D) BLV 10 mg for 96W. All patients were followed for up to 48W post-EOT (FU-48). The primary endpoint was the proportion with undetectable HDV RNA (&lt; lower limit of quantification (LLOQ), target not detected; LLOQ, 50 IU/mL; limit of detection, 6 IU/mL) at W24 post-EOT (FU-24) with predefined comparisons between arms C and D. Composite response was defined as undetectable HDV RNA and alanine aminotransferase (ALT) normalisation; other endpoints included ALT normalisation, change in liver stiffness (LS) by transient elastography, and hepatitis B surface antigen (HBsAg) loss. 34% had compensated cirrhosis with mean (SD) LS of 13.1 (7.7) kPa, HDV RNA of 5.3 (1.2) log₁₀ IU/mL, and ALT of 114 (94.8) U/L; 48% were on nucleos(t)ide analogue therapy, and 48% were interferon experienced. At FU-48, undetectable HDV RNA was achieved in 6/24 of arm A, 13/50 of arm B, 23/50 of arm C, and 6/50 of arm D (arm C vs D, P = 0.0003) (figure 1). At FU-48, 42% and 25% had ALT normalisation and achieved the composite endpoint in arm A; 38%, 22% in arm B; 46%, 40% in arm C; and 22%, 8% in arm D, respectively (arm C vs D, P &lt;0.05). In BLV-treated arms, at FU-48, least-square mean LS was improved vs baseline (arm A, −0.3; arm B, −2.4; arm C, −2.5; arm, D −0.8). HBsAg loss at FU-48 was observed in BLV-treated arms (arm A, 0%; arm B, 10%; arm C, 4%; arm D, 2%). BLV was well tolerated. One participant discontinued BLV due to a BLV-related adverse event; 3 experienced BLV-related serious adverse events during posttreatment. Combination therapy of BLV 10 mg with PegIFN resulted in the highest rates of undetectable HDV RNA at EOT and FU-24 (sustained through FU-48), providing a viable finite treatment option for patients with compensated CHD.