Delving into the Latest Updates on Besifovir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Besifovir dipivoxil, Besivo, ANA-380

+ [1]

Target

HBV pol

Action

inhibitors

Mechanism

HBV pol inhibitors(HBV DNA Polymerase inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication

Hepatitis B, Chronic

Inactive Indication-

Originator Organization

LG Life Sciences Ltd.

Active Organization

Ildong Pharmaceutical Co., Ltd.

Inactive Organization

LG Life Sciences Ltd.

License Organization

Ildong Pharmaceutical Co., Ltd.

LG Chem Ltd.

Drug Highest PhaseApproved

First Approval Date

South Korea (01 Mar 2017),

Hepatitis B, Chronic

Regulation-

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Structure/Sequence

Molecular FormulaC10H14N5O4P

InChIKeyKDNSSKPZBDNJDF-UHFFFAOYSA-N

CAS Registry441785-25-7

: Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB). However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB.

Methods:

: We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes.

Results:

: A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (-0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15.

Conclusions:

: BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.

01 Nov 2022·Liver International

Similar risk of kidney function decline between tenofovir alafenamide and besifovir dipivoxil maleate in chronic hepatitis B

Article

Author: Kim, Beom Seok ; Lee, Jung Il ; Ahn, Sang Hoon ; Kim, Seung Up ; Lee, Hyun Woong ; Jung, Chan‐Young ; Kim, Hyung Woo

Abstract:

Background and Aims:

Although tenofovir alafenamide (TAF) and besifovir dipivoxil maleate (BSV) are potent antiviral agents in the treatment of chronic hepatitis B (CHB) infection, their renal safety profiles have not been previously compared. This study compared the risk of kidney function decline among patients with treatment‐naïve CHB treated with TAF or BSV.

Methods:

This multicenter, retrospective, longitudinal cohort study included 556 patients with treatment‐naïve CHB treated with TAF (n = 366) or BSV (n = 190) between November 2017 and August 2021. The primary outcome was chronic kidney disease (CKD) progression, defined as an increase in CKD stage by at least one stage for at least three consecutive months.

Results:

1:1 Propensity score matching yielded 154 patients in each treatment group. The mean estimated glomerular filtration rate (eGFR) was 100.4 vs. 100.3 ml/min/1.73 m2 in the TAF and BSV groups respectively. A total of 25 patients developed a progression in CKD stage ≥1, of which 13 and 12 patients were from the TAF and BSV treated groups respectively (3.1 vs. 3.3 per 1000 person‐years; p = .751). The unadjusted hazard ratio for risk of progression in CKD stage ≥1 of the BSV group (vs. the TAF group) was 1.13 (95% confidence interval, 0.50–2.58; p = .758). This association persisted even after adjusting for potential confounders. Virological, serological and biochemical responses were also similar between the two treatment groups (all p > .05).

Conclusions:

TAF and BSV showed a similar risk of kidney function decline in patients with treatment‐naïve CHB. Further prospective randomized studies are warranted for validation.

01 Feb 2022·Journal of gastroenterology and hepatologyQ3 · MEDICINE

Besifovir therapy improves hepatic histology and reduces covalently closed circular DNA in chronic hepatitis B patients

Q3 · MEDICINE

Article

Author: Kim, Dong Joon ; Park, Eun‐Sook ; Sohn, Joo Hyun ; Um, Soon Ho ; Jin, So‐Young ; Kim, Kyun‐Hwan ; Yim, Hyung Joon ; Jung, Young Kul ; Jang, Jae Young ; Ahn, Sang Hoon ; Kim, Won

Abstract:

Background and Aim:

Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy.

Methods:

This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed.

Results:

A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow‐up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349).

Conclusions:

The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients.

100 Deals associated with Besifovir

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Besifovir	J05AB	DB15671

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis B, Chronic	South Korea	Ildong Pharmaceutical Co., Ltd.	01 Mar 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04202536 (Pubmed \| Clin Mol Hepatol)	Phase 4	Hepatitis B, Chronic hepatitis B virus (HBV) DNA	153	Besifovir 150 mg	ywfqdpumqs(qiyprwjkil) = mddhuvjlok tleyiyslxh (zgpgchkjle )	Positive	17 Jan 2025
				Tenofovir Disoproxil Fumarate 300 mg	ywfqdpumqs(qiyprwjkil) = uazoqpfjwk tleyiyslxh (zgpgchkjle )
EASL2021	Not Applicable	Hepatitis B, Chronic	153	Besifovir dipivoxil maleate (BSV)	vhefoxqrmq(nzvupcvbfm) = Patients who switched to BSV experienced improvements in bone turnover biomarkers while those who maintaining TDF worsened kmwzralgkq (tenvhgcpeg )	Positive	23 Jun 2021
				Tenofovir disoproxil fumarate (TDF)
NCT01937806 (Pubmed \| Clin Mol Hepatol) Manual	Phase 3	Hepatitis B, Chronic	197	Besifovir	zzrqixpjnc(kxmormfdcb) = kxjtytqdhi prwetbbgpu (qgfvppeizt )	Superior	01 Apr 2021
				tenofovir disoproxil fumarate+Besifovir	zzrqixpjnc(kxmormfdcb) = ravotyawwt prwetbbgpu (qgfvppeizt )
NCT01937806 (Pubmed \| Am J Gastroenterol)	Phase 3	Hepatitis B, Chronic	197	Besifovir dipivoxil maleate	yqegthgrqe(risrbogltt) = zwexhxzarr qkgupddawp (ladznichoz )	Positive	01 Aug 2020
				Tenofovir disoproxil fumarate followed by Besifovir dipivoxil maleate	yqegthgrqe(risrbogltt) = qnxcamggod qkgupddawp (ladznichoz )
NCT01937806 (Pubmed \| Clin Gastroenterol Hepatol) Manual	Phase 3	Hepatitis B, Chronic	197	Besifovir Dipivoxil Maleate	hpkowwouyx(nulnbldvhq) = bshgwdjdub wfezutfzgy (nfmsdqdcqz ) View more	Similar	01 Aug 2019
				Tenofovir Disoproxil Fumarate+Besifovir	hpkowwouyx(nulnbldvhq) = qvpduwtevn wfezutfzgy (nfmsdqdcqz ) View more
EASL2019	Phase 3	Hepatitis B, Chronic	197	Besifovir dipivoxil maleate (BSV)	jhjpezotwu(fwlwebizzk) = jybbtkbohj tagjwqhdap (xgljzhwnne )	-	12 Apr 2019
				Tenofovir disoproxil fumarate (TDF)	jhjpezotwu(fwlwebizzk) = smpxaudadc tagjwqhdap (xgljzhwnne )
NCT00895596 \| NCT01242787 (Pubmed \| Hepatology)	Phase 1/2	Hepatitis B, Chronic	65	LB80380	hsvavcgtdy(uccvbucpij) = 44.6% of patients experienced mild and self-limiting adverse events, none of which were attributed to the study drug gcfgbbjcxc (leckvwgbyz )	Positive	01 Mar 2010
Pubmed \| Antivir Ther	Phase 1/2	Hepatitis B, Chronic hepatitis B e antigen	29	LB80380 30 mg	jqwwpjoigc(yauohyrxes) = bibnnmqhdo nmfqxylyfu (wjlknnrkav )	-	01 Nov 2006
				LB80380 60 mg	jqwwpjoigc(yauohyrxes) = csbtmepmkk nmfqxylyfu (wjlknnrkav )