S2694 Achieving Undetectable Hepatitis Delta Virus RNA at End of Therapy With Bulevirtide 10 Mg/day With or Without PegIFNα Is Strongly Associated With Posttreatment Virologic Response in Chronic Hepatitis Delta

Introduction: Bulevirtide (BLV) 2 mg is approved for chronic hepatitis delta (CHD) treatment in Europe, Australia, and Russia. In an integrated analysis of BLV 10 mg monotherapy or in combination with pegylated interferon alpha (PegIFNα), we explored whether hepatitis delta virus (HDV) RNA levels undetectable (target not detected; TND) vs below the lower limit of quantitation (<LLOQ; target detected [TD]) at end of treatment (EOT) affect posttreatment (PT) virologic response. Methods: A pooled analysis of data was performed from patients who completed 2 or 3 years of BLV 10 mg/day (d) with or without PegIFNα in the MYR204 Phase 2 and MYR301 Phase 3 studies. Patients received (A) BLV 10 mg + PegIFNα for 48 weeks (W) followed by 48 W of monotherapy with BLV 10 mg (n = 50), (B) BLV 10 mg for 96W (n = 100), or (C) BLV 10 mg for 144 W (n = 50). Pts were followed for up to 48 W after EOT (follow-up [FU]48). HDV RNA levels were determined by RT-qPCR using RoboGene 2.0 (LLOQ 50 IU/mL, limit of detection 6 IU/mL). Virologic response rates at FU48 were compared between patients with undetectable HDV RNA and those with HDV RNA < LLOQ, TD at EOT. Results: Demographics were similar across groups. At EOT, 49% (97/200) achieved undetectable HDV RNA: (A) 70% (35/50), (B) 37% (37/100), and (C) 50% (25/50); 24% (48/200) had < LLOQ, TD: (A) 16% (8/50), (B) 30% (30/100), and (C) 20% (10/50). At FU48, undetectable HDV RNA was observed in 25% (49/200) overall: (A) 23/50 (46%) of patients receiving combination therapy, (B) 14% (14/100) of patients receiving 2 years of BLV monotherapy, and (C) 24% (12/50) of patients receiving 3 years of BLV monotherapy. 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 < LLOQ, TD at FU48: (A) 6% (2/35), (B) 9% (3/37), and (C) 4% (1/25). Of those who had < LLOQ, TD at EOT, only 6% (3/48) had undetectable HDV RNA (1 per group) and 4% (2/48) remained < LLOQ, TD at FU48, while 71% (34/48) had HDV RNA > LLOQ: (A) 62.5% (5/8), (B) 80% (24/30), and (C) 50% (5/10); during FU, 9 discontinued the study early. Conclusion: In patients with compensated CHD, achieving undetectable HDV RNA with TND at EOT is associated with virologic suppression at 48 W PT. Combination therapy with BLV 10 mg/d and PegIFNα and longer treatment with BLV monotherapy were associated with higher rates of undetectable HDV RNA at EOT and FU48. Pts with HDV RNA < LLOQ, TD at EOT are likely to have HDV RNA rebound off therapy.