A Phase 3 Study of Tenofovir Alafenamide Compared with Tenofovir Disoproxil Fumarate in Patients with Hbeag-Negative, Chronic Hepatitis B: Week 48 Efficacy and Safety Results

Buti, Marı́a; Gane, Ed; Seto, Wai‐Kay; Chan, H.L.Y.; Chuang, Wan‐Long; Степанова, Т. Ю.; Hui, Aric Josun; Lim, Yong Sung; Mehta, R.; Janssen, H.L.A.; Sk, Acharya; Flaherty, John F.; Massetto, Benedetta; Cathcart, A.; Dinh, Phillip; Subramanian, G. Mani; McHutchison, John G.; Pan, C.; Brunetto, M.R.; Izumi, N.; Marcellin, Patrick

doi:10.1016/s0168-8278(16)01637-8

Cited by 14 publications

(12 citation statements)

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“…In recent randomised phase 3 studies, the efficacy of TAF at week 48 on virological response was non‐inferior to TDF for both HBeAg‐positive and ‐negative patients. Patients with TAF treatment had significant improvements in both renal and bone safety than TDF …”

Section: Novel Approaches: Direct Acting Anti‐virals (Daa)mentioning

confidence: 99%

“…Patients with TAF treatment had significant improvements in both renal and bone safety than TDF. 62,63 Besifovir (LB80380) is a novel and potent guanosine analogue with rapid intracellular phosphorylation to inhibit HBV replication. It also has potent anti-HBV activity, irrespective wild type virus or virus resistant to approved nucleos(t)ide analogues.…”

Section: Potent Polymerase Inhibitorsmentioning

confidence: 99%

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Review article: novel therapies for hepatitis B virus cure – advances and perspectives

Lin

Kao

2016

Aliment Pharmacol Ther

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Summary Background Current anti‐viral therapies, interferon and nucleos(t)ide analogues, have been proven to reduce the progression of chronic hepatitis B (CHB). However, covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) persists, resulting in viral relapse after the discontinuation of treatment. Aim To discuss and review novel therapies for chronic hepatitis B infection. Methods Recent published studies which searched from PubMed were comprehensive reviewed. The key words include chronic hepatitis B, hepatitis B virus cure, covalently closed circular DNA, direct acting anti‐virals and host targeting agents. Results Several novel agents through viral and host targets approaches are under investigations towards functional cure of HBV. On the one hand, direct acting anti‐virals targeting virus itself, such as HBV new polymerase inhibitor, entry inhibitor, engineered site‐specific nucleases and RNA interference, could inhibit amplification of cccDNA as well as intrahepatic HBV infection and eliminate or silence cccDNA transcription. Inhibitors of HBV nucleocapsid assembly suppress capsid formation and prevent synthesis of HBV DNA. On the other hand, host targeting agents (HTA) include lymphotoxin‐β receptor agonist, toll‐like receptor agonist, immune checkpoint inhibitors and adenovirus‐based therapeutic vaccine. Through enhancing innate and adaptive immune responses, these agents could induce noncytolytic destruction of cccDNA or attack HBV‐infected hepatocytes. Conclusion With these promising approaches, we hope to reach global hepatitis B virus control in the middle of this century.

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Section: Novel Approaches: Direct Acting Anti‐virals (Daa)mentioning

confidence: 99%

Section: Potent Polymerase Inhibitorsmentioning

confidence: 99%

Review article: novel therapies for hepatitis B virus cure – advances and perspectives

Lin

Kao

2016

Aliment Pharmacol Ther

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“…I pazienti in trattamento con ETV ad "alto rischio" e quelli in trattamento con TDF a "basso rischio" devono essere controllati ogni 3 mesi per il primo anno e ogni 6 mesi successivamente se non si osserva un peggioramento della funzione renale, mentre i pazienti in trattamento con TDF ad "alto rischio" devono essere monitorati ogni mese per i primi 3 mesi, poi ogni 3 mesi fino alla fine del primo anno e successivamente ogni 6 mesi in assenza di peggioramento della funzione renale [2]. Per far fronte a queste problematiche di tossicità correlate all'impiego di TDF, è stato recentemente sviluppato tenofovir alafenamide (TAF) [46][47][48][49][50]. Negli studi a 48 settimane in pazienti con epatite cronica B, TAF ha confermato una minore tossicità renale e ossea rispetto a TDF [49,50].…”

Section: Figura 12unclassified

“…Per far fronte a queste problematiche di tossicità correlate all'impiego di TDF, è stato recentemente sviluppato tenofovir alafenamide (TAF) [46][47][48][49][50]. Negli studi a 48 settimane in pazienti con epatite cronica B, TAF ha confermato una minore tossicità renale e ossea rispetto a TDF [49,50]. Tuttavia, a fronte dei dati di efficacia e sicurezza più che decennali otte-nuti nella pratica clinica con ETV [51][52][53][54][55][56][57][58][59][60], ci si chiede quale possa essere l'ambito d'impiego del TAF.…”

Section: Figura 12unclassified

Efficacia e sicurezza di entecavir dopo switch da tenofovir per comparsa di effetti collaterali renali: uno studio multicentrico italiano, di pratica clinica, su 103 pazienti con epatite cronica B

Viganò

2016

ABTPN

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Entecavir (ETV) e tenofovir disoproxil fumarato (TDF) rappresentano gli analoghi nucleos(t)idici di III generazione raccomandati in prima linea nei pazienti con epatite cronica B. Entrambi si caratterizzano per un'elevata efficacia e per il rischio pressoché nullo di sviluppo di farmaco-resistenza, tuttavia con l'impiego di TDF sono stati segnalati eventi avversi renali, come la riduzione del filtrato glomerulare (eGFR), l'ipofosfatemia, l'iperfosfaturia e la sindrome di Fanconi, e scheletrici quali osteomalacia e osteoporosi. In questo studio italiano di coorte, multicentrico, sono stati arruolati 103 pazienti con epatite cronica B [età media 63 anni, 83% maschi, 49% cirrotici, 97% HBeAg-negativi, 75% trattati con lamivudina (LMV), 46% con pregressa LMV-resistenza (R), 71% trattati con adefovir dipivoxil (ADV), 94% con ALT normali e 98% con HBV DNA <13 UI/mL] che sono passati a ETV per l'evidenza di una compromissione della funzione renale glomerulare e/o tubulare durante i 35 mesi (range: 3-112) di terapia con TDF (iniziato o ridotto durante il trattamento a 245 mg ogni 48/72 ore nel 40% dei casi). Al basale (inizio della terapia con ETV), una riduzione di eGFR <90 mL/minuto era presente in 94 Efficacia e sicurezza di entecavir dopo switch da tenofovir per comparsa di effetti collaterali renali: uno studio multicentrico italiano, di pratica clinica, su 103 pazienti con epatite cronica B

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“…These data reinforce the need for monitoring and dose adjustment of TDF in patients with reduced eGFR. With the anticipated approval of tenofovir alafenomide (TAF), a phosphonate prodrug of tenofovir that efficiently delivers active drug to hepatocytes, thereby reducing systemic tenofovir exposures, the renal concerns are likely to be reduced [8]. Nevertheless, in clinical scenarios where medication costs may influence use of TAF versus TDF, these ''real-world'' cohorts using TDF identify patients at higher risk of renal toxicity and thus might be targeted for TAF a priori.…”

mentioning

confidence: 99%

Real-World Experiences with Tenofovir Disoproxil Fumarate: Is this the “B-Ticket”?

Terrault

2016

Dig Dis Sci

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The preferred options for treatment of chronic hepatitis B viral (HBV) infection in countries without resource constraints are peginterferon, entecavir, or tenofovir disoproxil fumarate (TDF) [1,2]. For most clinicians, peginterferon is infrequently considered due to the greater complexity of monitoring, higher frequency of adverse effects and patient preference, which narrows the treatment options to TDF or entecavir. In the registration trials of treatment-naïve patients with chronic hepatitis B, both TDF and entecavir demonstrated high rates of on-treatment HBV DNA suppression and low rates of viral resistance coupled with excellent safety [3,4]. Given that TDF and entecavir have been approved therapies for HBV for more than a decade, data derived from ''real-world'' cohort studies have helped fill knowledge gaps regarding the use of these drugs in clinical practice. In the case of TDF, the issues of particular interest include: (1) the efficacy of TDF across a wider spectrum of patients including those less adherent than patients in clinical trials, and (2) the risks associated with longer-term use of TDF, especially the frequency of viral resistance and the risk of renal and bone toxicity.Patients participating in clinical trials are a select group-typically healthier than many patients in the clinic, with fewer comorbidities and higher rates of adherence. The registration trials for TDF required a estimated glomerular filtration rate (eGFR) [70 ml/min, absence of anemia, neutropenia, and liver decompensation or presence of unstable comorbidities [3]. In practice, patient complexity can be greater, comorbidities not always optimized, and adherence less assured. Understanding how antivirals perform under these less than ideal circumstances is important. The ideal ''real-world'' study would prospectively enroll consecutive patients and account for all patients at study end, provide intent-to-treat as well as perprotocol analyses, and include details of treatment failures, including reasons for treatment discontinuation. The ''realworld'' cohorts included in this issue of Digestive Diseases and Sciences-GEMINIS from Germany [5] and VIREAL from France [6]-partially meet these high standards. Regardless, some important practical messages can be gleaned from their analyses.The VIREAL and GEMINIS cohorts enrolled [800 patients from diverse practice settings who were newly initiated on TDF therapy [5,6]. Treatment-naïve and experienced subjects were included, with a substantial proportion of the treatment-experienced patients transitioning from another nucleos(t)ide analog therapy to TDF and having low or undetectable HBV DNA levels at the time of TDF initiation. Hypertension, diabetes, renal disease, cardiovascular diseases, and other comorbidities were present in *40 % of patients [5] with up to 28 % having eGFR \90 ml/min [6]. Although the intent of the study was to follow patients for 3 years, both cohorts suffered from patient attrition, leading to incomplete reporting of virologic and safety data. The primary...

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A Phase 3 Study of Tenofovir Alafenamide Compared with Tenofovir Disoproxil Fumarate in Patients with Hbeag-Negative, Chronic Hepatitis B: Week 48 Efficacy and Safety Results

Cited by 14 publications

References 0 publications

Review article: novel therapies for hepatitis B virus cure – advances and perspectives

Review article: novel therapies for hepatitis B virus cure – advances and perspectives

Efficacia e sicurezza di entecavir dopo switch da tenofovir per comparsa di effetti collaterali renali: uno studio multicentrico italiano, di pratica clinica, su 103 pazienti con epatite cronica B

Real-World Experiences with Tenofovir Disoproxil Fumarate: Is this the “B-Ticket”?

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