Explore the vast range of titles available.

BackgroundBulevirtide (BLV) is a first-in-class entry inhibitor for chronic hepatitis D (CHD) which was conditionally approved in the EU. Results from the Week 48 primary endpoint analysis for MYR301, a phase 3 randomized study, showed monotherapy with BLV at 2 or 10 mg/d given subcutaneously was superior to no active anti-HDV treatment e. Here, we present findings from the predefined week 96 interim analysis of this ongoing study.Methods150 patients with CHD were randomized and stratified: Arm A: no active anti-HDV treatment for 48 weeks followed by BLV 10mg/d for 96 weeks (n=51), and Arms B or C: immediate treatment with BLV at 2 mg/d (n=49) or 10 mg/d (n=50), respectively, each for 144 weeks, with follow-up of 96 weeks after end of treatment. The combined response was defined as undetectable HDV RNA or decrease by ≥2 log10 IU/mL from baseline and ALT normalization; other endpoints included viral response, ALT normalization, log10 change in HDV RNA and change in liver stiffness by transient elastography.ResultsAt W24, 62% of participants were VR, of which 30 had ALT WNL, 22 were PR, of which 12 had ALT WNL, and 14 were NR, of which 2 had ALT WNL. (IDDF2024-ABS-0267 Table 1) Of the 36 NR or PR at W24 vs VR, mean baseline HDV RNA and median ALT at W96 were as follows: VR [5.1 log10 IU/mL, 77 U/mL], PR [4.9 log10 IU/mL, 120 U/mL], and NR [4.4 log10 IU/mL, 156 U/mL]. Of 22 PR participants at W24, 18 became VR by W96; 15 with ALT WNL) and 3 remained PR; 2 with ALT WNL.Abstract IDDF2024-ABS-0267 Table 1Shift Table for Non- and Partial Responders at Week 24 Through Week 48 and 96 BLV 2 mg Week 24 HDV RNA BLV 10 mg Week 24 HDV RNA BLV 2mg = 10 mg Week 24 HDV RNA NR PR VR NR PR VR NR PR VR n=10 n=12 n=25 n=4 n=10 n=33 n=14 n=22 n=58W48 HDV RNA Nonresponder8 (80)1 (8.3)0 (0)3 (75)0 (0)0 (0)11 (78.6)1 (4.6)0 (0) Partial Responder1 (10)0 (0)2 (8)0 (0)5 (50)1 (3)1 (7.1)5 (22.7)3 (5.2) Responder1 (10)11 (91.7)23 (92)1 (25)5 (50)32 (97)2 (14.3)16 (72.7)55 (94.8)W96 HDV RNA Nonresponder4 (40)1 (8.3)0 (0)1 (25)0 (0)0 (0)5 (35.7)1 (4.6)0 (0) Partial Responder3 (30)0 (0)2 (8)0 (0)3 (30)2 (6.1)3 (21.4)3 (13.6)4 (6.9) Responder3 (30)11 (91.7)23 (92)3 (75)7 (70)31 (93.9)6 (42.9)18 (81.8)54 (93.1)ConclusionsBLV continues to be safe and well tolerated as monotherapy for CHD through Week 96. Virological and biochemical responses increased with longer-term therapy.

In MYR301, a Phase 3 study evaluating bulevirtide (BLV) monotherapy for 2–3 years, BLV treatment was safe and effective through 144 weeks (W) in patients with compensated chronic hepatitis delta (CHD). We present final MYR301 results through follow-up at 96W after end of treatment (EOT; FU96).Patients (N=150) were randomised to treatment with BLV 2 or 10 mg/day for 144W or to 48W of delayed treatment followed by BLV 10 mg/day for 96W (DT-to-10 mg) and 96W posttreatment FU. Efficacy endpoints included virologic response (VR; undetectable hepatitis delta virus [HDV] RNA or ≥2 log1 0 IU/mL decline from baseline), combined response (CR; VR and alanine aminotransferase [ALT] normalisation), ALT normalisation, undetectable HDV RNA, and hepatitis B surface antigen (HBsAg) loss. The primary analysis was intention to treat, with missing data considered failures.Baseline characteristics were similar across groups. Most patients (92%) remained in the study at EOT; 72% and 57% completed FU48 and FU96. CR rates in the 2, 10, and DT-to-10 mg groups declined from 57%, 54%, and 56% at EOT to 24% in each group at FU96. HDV RNA undetectability rates in these groups were 29%, 50%, and 52% at EOT and 20%, 22%, and 20% at FU96. Of the total 64 patients with undetectable HDV RNA at EOT and available FU data, 23 (36%) had sustained undetectable HDV RNA through FU96 and 41 had viral relapse, which occurred in 38 (93%) by FU24 and none after FU48. Sustained posttreatment undetectable HDV RNA was more frequent with longer on-treatment continuous HDV RNA undetectability at EOT: ≥96W, 9/10 (90%); ≥48W-to-<96W, 11/22 (50%); 0-to-<48W, 3/32 (9%). Posttreatment HBsAg loss occurred in 3 patients. Posttreatment, 14/142 (10%) patients had ALT >10 × the upper limit of normal (ULN). Posttreatment hepatic serious adverse events (SAEs) were reported in 20/142 (14%) patients: 7 had ALT >10 × ULN, 15 had HDV rebound (HDV RNA increased ≥2 log1 0 IU/mL from EOT), and 4 had liver-related hospitalisation; 1 additional patient experienced nonserious ascites. The hepatic SAEs resolved in 17/20 (85%) patients, ≥16 of whom restarted BLV.In patients with CHD treated with BLV monotherapy for 96W or 144W, response rates decreased after treatment discontinuation. However, a subset of patients maintained undetectable HDV RNA for 2 years posttreatment, which was associated with longer duration of continuous on-treatment undetectability. Posttreatment viral relapse occurred only in year 1 after EOT and may be associated with hepatitis flares.

In the Phase 3 MYR301 study, a subset of patients with chronic hepatitis delta (CHD) receiving bulevirtide (BLV) monotherapy achieved undetectable hepatitis delta virus (HDV) RNA by end of treatment (EOT, 2–3 years) and maintained undetectable viraemia at follow-up (FU) 48 weeks (W) after EOT. We present predictors of sustained HDV RNA undetectability through FU48 after 96W or 144W of BLV treatment.Patients with CHD (n=149) in MYR301 were randomised to treatment with BLV 2 or 10 mg/day for 144W, or delayed treatment for 48W followed by BLV 10 mg/day for 96W (DT-to-10 mg). All patients were to be followed through FU48. Logistic regression modelling (adjusted for treatment group) was evaluated via odds ratios (OR [95% CI]) for potential predictors of sustained HDV RNA undetectability (defined as less than the lower limit of quantitation [target not detected at follow-up]) through FU48 in those with undetectable viraemia at EOT.Baseline characteristics were similar between treatment arms. Overall, 65/149 (44%) patients achieved HDV RNA undetectability at EOT, of whom 23/64 (36%) had sustained undetectability through FU48. Sustained undetectability rates were higher in the immediate treatment (2 mg: 7/14, 50%; 10 mg: 10/25, 40%) vs DT-to-10 mg arms (6/26, 23%). Undetectability rates at EOT were higher in the BLV 10 mg arm, but relapse was less frequent among the few patients with HDV RNA undetectable in the BLV 2 mg arm. Baseline predictors of sustained undetectability posttreatment included baseline median HDV RNA <4.5 log1 0 IU/mL (OR [95% CI]: 6.2 [1.9, 20.8]; P=0.003) and lower baseline hepatitis B surface antigen (HBsAg) level (0.3 per log1 0 IU/mL [0.1, 0.8]; P=0.019). On-treatment predictors included greater duration of continuous undetectability at EOT (per additional week: 1.0 [1.0, 1.1]; P<0.0001), HBsAg loss or decrease by ≥1 log1 0 IU/mL (7.2 [1.2, 42.3]; P=0.030), and W144 antidrug antibody (ADA) incidence (10.2 [1.9, 55.7]; P=0.008). The proportion of patients with sustained posttreatment undetectability was highest (9/10 [90%]) in those with ≥96W of undetectability at EOT, 11/22 (50%) in those with ≥48 to <96W, and 3/32 (9%) in those with <48W. Of patients with ADA incidence by W144, 8/10 (80%) had sustained undetectability vs 15/54 (28%) of those without. Baseline cirrhosis was not a predictor of sustained posttreatment undetectability (13/32 [41%] with vs 10/32 [31%] without cirrhosis).In patients with CHD treated with BLV monotherapy for 96W or 144W, early and sustained HDV RNA undetectability predicted sustained undetectability during follow-up.

BackgroundBulevirtide (BLV) is conditionally approved in the EU for the treatment of chronic hepatitis D (CHD) based on surrogate endpoint results. Virologic responders (VR) to HDV therapy are defined as achieving undetectability or a ≥2-log10 IU/mL decline in HDV RNA from baseline (BL). However, it is unclear if patients who are early virologic nonresponders (NR) will benefit from continued therapy.MethodsMYR301 is a randomized study: BLV 2mg (Arm B) and BLV 10mg (Arm C) for 144W. Results from participants on treatment at 96W from Arm B + C were included in this analysis. Rates of participants achieving biochemical response (alanine transaminase [ALT] within normal limits [WNL]) were compared between NR, PR, and VR.ResultsBaseline characteristics were similar between groups and included: mean (SD) age 41.8 (8.4) years, 57% males, 83% White, 47% with compensated cirrhosis, mean (SD) HDV RNA 5.05 (1.34) log10 IU/mL, mean (SD) ALT 110.9 (69.0) U/L, mean (SD) LS of 15 (8.9) kPa; and 61% were on concomitant nucleos(t)ide analogues therapy. Of 150 patients, 143 (95%) completed 96 weeks of treatment. Week 96 efficacy responses were improved vs. Week 48 (IDDF2024-ABS-0266 Table 1). At Week 96, similar combined responses were seen in arms B and C. Viral and biochemical responses were also similar among arms B and C. BLV were safe and well tolerated; there were no drug discontinuations, serious AE (SAE) or deaths attributed to BLV. Increases in bile acids without a correlation to pruritus or other symptoms were noted with BLV treatment. Injection site reactions occurred in a higher proportion receiving 10 mg/d dosing.Abstract IDDF2024-ABS-0266 Table 1Efficacy and safety results for BLV at Weeks 48 and 96 Arm A Delayed Treatment/BLV 10 mg (N = 51) Arm B BLV 2 mg (N = 49) Arm C BLV 10 mg (N = 50) Week 48 Week 96 (48 week BLV 10 mg ) Week 48 Week 96 Week 48 Week 96 Combined Response:Responder n (%)1 (2)20 (39)22 (45)27 (55)24 (48)28 (56) 95% CI (%)(0.10)(26.54)(31, 60)(40, 69)(34, 63)(41, 70) Viral Response:Responder n (%)2 (4)46 (90)36 (73)37 (76)38 (76)41 (82) 95% CI (%)(0, 13)(79, 97)(59, 85)(61, 87)(62, 87)(69, 91) Undetectable HDV RNA:Responder n (%)012 (24)6 (12)10 (20)10 (20)18 (36) 95% CI (%)(0, 7)(13, 38)(5, 25)(10, 34)(10, 34)(23, 51) ALT normalization:Responder n (%)6 (12)22 (43)25 (51)31 (63)28 (56)32 (64) 95% CI (%)(4, 24)(29, 58)(36, 66)(48, 77)(41, 70)(49, 77) Change from BL in HDV RNA levels (log10 IU/mL):0.0-3.6-2.6-3.2-3.0-3.6Least square means (95% CI)(-0.4, 0.3)(-0.4, 3.3)(-3.0, -2.3)(-3.6, 2.8)(-3.4, -2.7)(-4, 3.2) Change from BL in HBsAg levels (log10 IU/mL):0.0-0.20.1-0.20.1-0.1Least square means (95% CI)(-0.1, 0.1)(-0.3, 0.0)(-0.0, 0.2)(-0.4, -0.1)(0.0, 0.2)(-0.3, 0.0) Change from BL in liver stiffness (kPa):0.9-3.0-3.1-4.0-3.2-4.7Least square means (95% CI)(-0.8, 2.6)(-4.6, -1.5)(-4.7, -1.5)(-5.6, -2.5)(-4.9, -1.5)(-6.3, -3.2) Adverse Events at Week 96 Number (%) of patients with:Any AE39 (77)47 (96)41 (84)47 (96)44 (88)48 (96)Any Grade ≥ 3-4 AE4 (8)7 (14)5 (10)9 (18)4 (8)8 (16)Any AE related to BLV022 (43)24 (49)25 (51)36 (72)36 (72)Any SAE1 (2)3 (6)12 (4)2 (4)1 (2)4 (8)BL, baseline, CI, confidence interval.Undetectable HDV RNA defined as below lower limit of quantification (target not detected). ALT normalization defined as: ≤31 U/L for females and ≤41 U/L for males (Russian sites): or ≤34 U/L for females and ≤49 U/L for males (all other sites). Confidence intervals were calculated using Clopper-Pearson (exact) for proportions. 1Includes 1 death due to plasma cell myeloma not related to study treatment.ConclusionsMost patients who were PR (75%) and a considerable portion who were NR (43%) to BLV at 24W achieved VR by W96, with ALT improvements occurring in all groups, including those who remained NR.