Safety and effectiveness of up to 3 years’ bulevirtide monotherapy in patients with HDV-related cirrhosis

Loglio, Alessandro; Ferenci, Péter; Renteria, Sara Colonia Uceda; Tham, Christine Y.L.; Scholtès, Caroline; Holzmann, Heidemarie; Boemmel, Florian van; Borghi, Marta; Perbellini, R.; Rimondi, Alessandro; Farina, Elisa; Trombetta, Elena; Manunta, Maria; Porretti, Laura; Prati, Daniele; Ceriotti, Ferruccio; Zoulim, Fabien; Bertoletti, Antonio; Lampertico, Pietro

doi:10.1016/j.jhep.2021.10.012

Cited by 54 publications

(57 citation statements)

References 10 publications

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“…The inhibition of cell reinfection and cell spread and the later onset of the antiviral effect could explain the HCV RNA reduction in the erlonitib 100 mg group observed only after the end of the 14-day treatment course. Indeed, a similar kinetic of viral load changes has been reported for both HCV and hepatitis delta virus entry inhibitors in patients and animal models, with an antiviral effect starting around 2 weeks after the treatment initiation and lasting several days or weeks after the end of treatment (30,(32)(33)(34)(35).…”

Section: Discussionsupporting

confidence: 59%

Safety and Antiviral Activity of EGFR Inhibition by Erlotinib in Chronic Hepatitis C Patients: A Phase Ib Randomized Controlled Trial

Saviano¹,

Habersetzer²,

Lupberger

et al. 2022

Clin Transl Gastroenterol

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INTRODUCTION:Significant hepatocellular carcinoma (HCC) risk persists after chronic hepatitis C (CHC) cure. Preclinical studies have shown that erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has an antiviral activity and HCC chemopreventive effect. Erlotinib is metabolized in the liver, and its safety in patients with CHC is unknown. This study aimed to assess the safety and antiviral activity of erlotinib in patients with CHC.METHODS:In this investigator-initiated dose-escalation phase Ib prospective randomized double-blind placebo-controlled study, noncirrhotic hepatitis C virus (HCV) patients received placebo or erlotinib (50 or 100 mg/d) for 14 days with a placebo-erlotinib ratio of 1:3. Primary end points were safety and viral load reduction at the end of treatment (EOT). The secondary end point was viral load reduction 14 days after EOT.RESULTS:This study analyzed data of 3 patients receiving placebo, 3 patients receiving erlotinib 50 mg/d, and 3 patients receiving erlotinib 100 mg/d. One grade 3 adverse event was reported in the placebo group (liver enzymes elevation), leading to treatment discontinuation and patient replacement, and 1 in the erlotinib 100 mg/d group (pericarditis), which was not considered to be treatment-related. Grade 2 skin rash was observed in 1 erlotinib 100 mg/d patient. No significant HCV-RNA level reduction was noted during treatment, but 2 of the 3 patients in the erlotinib 100 mg/d group showed a decrease of >0.5 log HCV-RNA 14 days after EOT.DISCUSSION:Erlotinib demonstrated to be safe in noncirrhotic CHC patients. An antiviral activity at 100 mg/d confirms a functional role of EGFR as an HCV host factor in patients. These results provide perspectives to further study erlotinib as an HCC chemopreventive agent in patients with CHC.

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Section: Discussionsupporting

confidence: 59%

Safety and Antiviral Activity of EGFR Inhibition by Erlotinib in Chronic Hepatitis C Patients: A Phase Ib Randomized Controlled Trial

Saviano¹,

Habersetzer²,

Lupberger

et al. 2022

Clin Transl Gastroenterol

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“…Combined response, that is ALT normalisation and a > 2log decline of HDV‐RNA was observed in 7/22 (32%) patients at week 24, in 10/20 (50%) at week 36, in 12/20 (60%) at week 48 and 8/13 (62%) at week 60. Overall, a total of seven patients achieved HDV‐RNA undetectability: One at week 24, three at week 36, one at week 48, one at week 60 and one additional after a treatment period of 100 weeks 16,22 . No significant changes in HBsAg levels were observed during BLV therapy.…”

Section: Resultsmentioning

confidence: 97%

Response‐guided long‐term treatment of chronic hepatitis D patients with bulevirtide—results of a “real world” study

Jachs

Schwarz²,

Panzer

et al. 2022

Aliment Pharmacol Ther

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Summary Background and Aim Bulevirtide (BLV) blocks the uptake of the hepatitis D virus (HDV) into hepatocytes via the sodium/bile acid cotransporter NTCP. BLV was conditionally approved by the EMA but real‐life data on BLV efficacy are limited. Methods Patients were treated with BLV monotherapy. Patients who did not achieve further decreases in HDV‐RNA after 24 weeks were offered PEG‐IFN as an add‐on therapy in a response‐guided manner. Results Twenty‐three patients (m: 10, f: 13; mean age: 47.9 years, cirrhosis: 16; median ALT: 71 IU/ml; median HDV‐RNA: 2.1 × 105copies/ml) started BLV monotherapy (2 mg/day: 22; 10 mg/day: 1). Twenty‐two completed ≥24 weeks of treatment (24–137 weeks): Ten (45%) were classified as BLV responders at week 24. BLV was stopped in two patients with >6 months HDV‐RNA undetectability, but both became HDV‐RNA positive again. One patient was transplanted at week 25. One patient terminated treatment because of side effects at week 60. Ten patients are still on BLV monotherapy. Adding PEG‐IFN in eight patients induced an HDV‐RNA decrease in all (1.29 ± 0.19 [SD] log within 12 weeks). HDV‐RNA decreased by >2log or became undetectable in 45%(10/22), 55%(11/20), 65% (13/20) and 69% (9/13); and ALT levels normalised in 64% (14/22), 85% (17/20), 90% (18/20) and in 92% (12/13) patients at weeks 24, 36, 48 and 60, respectively. Portal pressure decreased in 40% (2/5) of patients undergoing repeated measurement under BLV therapy. Conclusion Long‐term BLV monotherapy is safe and effectively decreases HDV‐RNA and ALT—even in patients with cirrhosis. The optimal duration of BLV treatment alone or in combination with PEG‐IFN remains to be established. An algorithm for a response‐guided BLV treatment approach is proposed.

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“…Real-world experiences on the use of BLV are sparse [ 20 , 21 , 22 , 23 , 24 , 25 ]. We are the first to report the real-world safety and efficacy of BLV at the approved dose of 2 mg/day in combination with TDF over the observation period of 24 weeks according to treatment arm I of the MYR202 trial in a cohort of CHD patients without a disease-modifying SNP in SLC10A1 .…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Bulevirtide plus Tenofovir Disoproxil Fumarate in Real-World Patients with Chronic Hepatitis B and D Co-Infection

et al. 2022

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Background: The hepatitis B and D virus (HBV/HDV) hepatocyte entry inhibitor bulevirtide (BLV) has been available in Europe since July 2020, after the registrational trial MYR202. Real-life data on the efficacy and safety of BLV are sparse. Methods: We have analysed the course of treatment with BLV (2 mg/day) plus tenofovir disoproxil fumarate (TDF) (245 mg/day) in patients with chronic hepatitis delta (CHD). Virologic (≥2 log reduction in HDV RNA or suppression of HDV RNA below the lower limit of detection) and biochemical (normalisation of serum ALT) treatment responses after 24 weeks were defined according to the MYR202 trial. Results: Seven patients were recruited (four with liver cirrhosis Child–Pugh A). After 24 weeks, a virologic response was observed in five of seven and a biochemical response was seen in three of six patients with elevated serum ALT at baseline. Extended treatment data > 48 weeks were available in three cases: two presented with continuous virologic and biochemical responses and in one individual an HDV-RNA breakthrough was observed. Adverse effects were not recorded. Conclusions: The first real-life data of the approved dosage of 2 mg of BLV in combination with TDF confirm the safety, tolerability, and efficacy of the registrational trial MYR202 for a treatment period of 24 weeks and beyond.

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Safety and effectiveness of up to 3 years’ bulevirtide monotherapy in patients with HDV-related cirrhosis

Cited by 54 publications

References 10 publications

Safety and Antiviral Activity of EGFR Inhibition by Erlotinib in Chronic Hepatitis C Patients: A Phase Ib Randomized Controlled Trial

Safety and Antiviral Activity of EGFR Inhibition by Erlotinib in Chronic Hepatitis C Patients: A Phase Ib Randomized Controlled Trial

Response‐guided long‐term treatment of chronic hepatitis D patients with bulevirtide—results of a “real world” study

Efficacy and Safety of Bulevirtide plus Tenofovir Disoproxil Fumarate in Real-World Patients with Chronic Hepatitis B and D Co-Infection

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