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Conference Paper: Safety and antiviral activity of VIR-2218, an X-targeting RNAi therapeutic, in participants with chronic hepatitis B infection: week 48 follow-up results
Title | Safety and antiviral activity of VIR-2218, an X-targeting RNAi therapeutic, in participants with chronic hepatitis B infection: week 48 follow-up results |
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Authors | |
Issue Date | 2021 |
Publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep |
Citation | International Liver Congress (ILC) 2021: beating liver disease together, Virtual Meeting, 23-26 June 2021. In Journal of Hepatology, 2021, v. 75 n. Suppl. 2, p. S287-S288 How to Cite? |
Abstract | ackground and aims: VIR-2218 is an investigational GalNAcconjugated small interfering ribonucleic acid (siRNA) therapeutic in development for functional cure of chronic hepatitis B virus infection (CHB). VIR-2218 was created using Enhanced Stabilization Chemistry Plus, which retains in vivo potency while reducing off-target effects. VIR-2218 targets a conserved region of the X gene and is designed to
silence all major HBV transcripts, from both cccDNA and integrated DNA, across all 10 HBV genotypes as a single siRNA. We present final safety and antiviral activity data from a Phase 2 trial of VIR-2218 in
participants with CHB.
Method: Non-cirrhotic, virologically suppressed participants received 2 subcutaneous doses of VIR-2218 or placebo on Day 1 and Day 29 (Week 4). HBeAg- participants received 20, 50, 100 or 200 mg, and HBeAg+ participants received 50 or 200 mg. Cohorts included 4 or 8 participants randomized 3:1 to VIR-2218 or placebo. Assessments included safety, HBsAg levels and other viral markers, with 12 weeks of follow-up after the 2nd dose for all participants and an additional 32-weeks follow-up for participants achieving prespecified HBsAg declines.
Results: Twenty-four CHB participants received VIR-2218 (18 HBeAg-; 6 HBeAg+). Maximum mean HBsAg log10 IU/ml declines in HBeAg- participants receiving 20, 50, 100, and 200 mg of VIR-2218
were 1.03, 1.23, 1.50, and 1.65, respectively. For the HBeAg+ participants receiving 50 and 200 mg of VIR-2218, the maximum mean HBsAg log10 IU/ml declines were 1.16 and 1.57, respectively. Most participants achieved maximum HBsAg decline by week 16. Most participants had levels of HBV DNA and HBV RNA |
Description | Oral presentation - Parallel Session: Viral hepatitis B-D: therapy - no. OS-44 |
Persistent Identifier | http://hdl.handle.net/10722/305524 |
ISSN | 2023 Impact Factor: 26.8 2023 SCImago Journal Rankings: 9.857 |
DC Field | Value | Language |
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dc.contributor.author | Gane, E | - |
dc.contributor.author | Lim, YS | - |
dc.contributor.author | Cloutier, D | - |
dc.contributor.author | Shen, L | - |
dc.contributor.author | Cathcart, A | - |
dc.contributor.author | Ding, X | - |
dc.contributor.author | Pang, P | - |
dc.contributor.author | Huang, S | - |
dc.contributor.author | Yuen, RMF | - |
dc.date.accessioned | 2021-10-20T10:10:37Z | - |
dc.date.available | 2021-10-20T10:10:37Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | International Liver Congress (ILC) 2021: beating liver disease together, Virtual Meeting, 23-26 June 2021. In Journal of Hepatology, 2021, v. 75 n. Suppl. 2, p. S287-S288 | - |
dc.identifier.issn | 0168-8278 | - |
dc.identifier.uri | http://hdl.handle.net/10722/305524 | - |
dc.description | Oral presentation - Parallel Session: Viral hepatitis B-D: therapy - no. OS-44 | - |
dc.description.abstract | ackground and aims: VIR-2218 is an investigational GalNAcconjugated small interfering ribonucleic acid (siRNA) therapeutic in development for functional cure of chronic hepatitis B virus infection (CHB). VIR-2218 was created using Enhanced Stabilization Chemistry Plus, which retains in vivo potency while reducing off-target effects. VIR-2218 targets a conserved region of the X gene and is designed to silence all major HBV transcripts, from both cccDNA and integrated DNA, across all 10 HBV genotypes as a single siRNA. We present final safety and antiviral activity data from a Phase 2 trial of VIR-2218 in participants with CHB. Method: Non-cirrhotic, virologically suppressed participants received 2 subcutaneous doses of VIR-2218 or placebo on Day 1 and Day 29 (Week 4). HBeAg- participants received 20, 50, 100 or 200 mg, and HBeAg+ participants received 50 or 200 mg. Cohorts included 4 or 8 participants randomized 3:1 to VIR-2218 or placebo. Assessments included safety, HBsAg levels and other viral markers, with 12 weeks of follow-up after the 2nd dose for all participants and an additional 32-weeks follow-up for participants achieving prespecified HBsAg declines. Results: Twenty-four CHB participants received VIR-2218 (18 HBeAg-; 6 HBeAg+). Maximum mean HBsAg log10 IU/ml declines in HBeAg- participants receiving 20, 50, 100, and 200 mg of VIR-2218 were 1.03, 1.23, 1.50, and 1.65, respectively. For the HBeAg+ participants receiving 50 and 200 mg of VIR-2218, the maximum mean HBsAg log10 IU/ml declines were 1.16 and 1.57, respectively. Most participants achieved maximum HBsAg decline by week 16. Most participants had levels of HBV DNA and HBV RNA <LOQ at baseline, and significant changes were not detected. Declines in qHBeAg and HBcrAg were observed in HBeAg+ subjects receiving 200 mg VIR-2218. No participants discontinued due to an adverse event (AE), and the majority of treatment emergent AEs were mild in severity. No clinically significant ALT elevations were observed. Conclusion: Two doses of VIR-2218 at 20–200 mg given 4 weeks apart were well tolerated in CHB participants. Substantial reductions in HBsAg were observed in both HBeAg- and HBeAg+ participants across all dose levels, suggesting that VIR-2218 may silence transcripts from both cccDNA and integrated DNA. The antiviral activity of VIR-2218 demonstrated in this study support continued development as part of combination regimens targeting functional cure. | - |
dc.language | eng | - |
dc.publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep | - |
dc.relation.ispartof | Journal of Hepatology | - |
dc.relation.ispartof | The International Liver Congress 2021 (ILC 2021) | - |
dc.title | Safety and antiviral activity of VIR-2218, an X-targeting RNAi therapeutic, in participants with chronic hepatitis B infection: week 48 follow-up results | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Yuen, RMF: mfyuen@hku.hk | - |
dc.identifier.authority | Yuen, RMF=rp00479 | - |
dc.description.nature | abstract | - |
dc.identifier.hkuros | 326623 | - |
dc.identifier.volume | 75 | - |
dc.identifier.issue | Suppl. 2 | - |
dc.identifier.spage | S287 | - |
dc.identifier.epage | S288 | - |
dc.publisher.place | Netherlands | - |
dc.identifier.partofdoi | 10.1016/S0168-8278(21)01842-0 | - |