P164 Achieving undetectable hepatitis delta virus RNA at end of therapy with bulevirtide 10 mg/day with or without pegylated interferon alpha is strongly associated with posttreatment virologic response in chronic hepatitis delta

<h3></h3> This integrated analysis of bulevirtide (BLV) 10 mg monotherapy or combined with pegylated interferon alpha (PegIFN) explored whether undetectable hepatitis delta virus (HDV) RNA levels (target not detected; TND) vs below the lower limit of quantification (&lt;LLOQ; target detected [TD]) at end of treatment (EOT) affect posttreatment virologic response for patients with compensated chronic hepatitis delta (CHD). Data were pooled from patients completing 2 or 3 years of BLV 10 mg/day ± PegIFN in the MYR204 Phase 2 and MYR301 Phase 3 studies. Patients received (A) BLV 10 mg + PegIFN for 48 weeks (W) followed by 48W of BLV 10 mg monotherapy (n=50), (B) BLV 10 mg for 96W (n=100), or (C) BLV 10 mg for 144W (n=50). Patient follow-up (FU) continued for 48W after EOT. HDV RNA levels were determined (LLOQ 50 IU/mL, limit of detection 6 IU/mL), and virologic response rates at FU48 were compared between patients with undetectable HDV RNA vs HDV RNA &lt;LLOQ, TD at EOT. Demographics were similar across groups: male (65%), White (85%), and mean (SD) age 41 (8.2) years; 41% had compensated cirrhosis, and 53% had prior interferon experience. Mean (SD) HDV RNA, alanine aminotransferase, and liver stiffness were 5.1 (1.38) log¹⁰ IU/mL, 109 (88.2) U/L, and 14.0 (9.11) kPa, respectively. At EOT, 48.5% (97/200) overall achieved undetectable HDV RNA: (A) 70% (35/50), (B) 37% (37/100), and (C) 50% (25/50). Additionally, 24% (48/200) had &lt;LLOQ, TD. At FU48, undetectable HDV RNA was observed overall in 25% (49/200) of patients, 23/50 (46%) of those receiving combination therapy, and 14% (14/100) and 24% (12/50) among those who received BLV monotherapy for 2 or 3 years. Of the patients with undetectable HDV RNA at EOT, 46% (45/97) maintained undetectable HDV RNA at FU48: (A) 60% (21/35), (B) 35% (13/37), and (C) 44% (11/25); 6% (6/97) had &lt;LLOQ, TD at FU48. Of those who had &lt;LLOQ, TD at EOT, 6% (3/48) had undetectable HDV RNA (1 in each group) and 4% (2/48) maintained &lt;LLOQ, TD at FU48, while 71% (34/48) had HDV RNA &gt;LLOQ. In patients with compensated CHD, undetectable HDV RNA with TND at EOT is strongly associated with virologic suppression at 48W posttreatment. BLV 10 mg/day and PegIFN combination therapy and longer treatment with BLV monotherapy had higher HDV RNA undetectability rates at EOT and FU48. Patients with HDV RNA &lt;LLOQ, TD at EOT are likely to have HDV RNA rebound off therapy.