만성B형간염의 치료에서 비리어드와 비교해 베시보의 유효성과 안전성(Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection)

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기사입력 2019.10.21 12:25 AM

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Background & Aims

Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea.

Methods

We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA <69 IU/mL or 400 copies/ml), bone mineral density (BMD), and renal outcomes for safety analysis. The main efficacy endpoint was the proportion of patients with a virologic response at week 48. After 48 weeks, TDF was switched to BSV (150 mg) for an additional 48 weeks.

Results

After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV-BSV and 85.7% of patients in the TDF-BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups.

Conclusions

BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes.

만성B형간염 치료의 주된 치료약물은 entecavir(ETV), 비리어드, tenofovir alafenamide(TAF)였다. 하지만 효과적인 바이러스 치료 후에도 일부 환자에서는 간부전이나 간암이 발생하고 있기 때문에 기존 치료 약물들은 한계가 있었다. 게다가 entecavir(ETV)는 약물 내성이 발생할 수 있고 비리어드는 신독성과 골밀도 감소가 발생할 수 있다. 베시보는 la 임상 및 llb임상에서 강력한 바이러스 억제 효과를 보였기 때문에 이번 연구에서는 국내 만성B형간염 환자들을 대상으로 베시보의 3상 시험을 진행했다.

핵심 메시지

1. 48주 치료 후에 항바이러스 유효성은 베시보와 비리어드가 비슷하며 베시보는 96주간 효과가 지속된다.
2. 비리어드와 비교해 베시보는 뼈와 신장에 대한 안전성이 더 우월하다.