Tenofovir Alafenamide Tablets (trade name: Vemlidy), known as the "strongest HBV drug in history", has been recommended by the latest European Association for the Study of the Liver (EASL) guidelines and American Association for the Study of Liver Diseases (AASLD) guidelines as a first-line therapy for the previously untreated chronic hepatitis B (CHB). With this, there are three first-line nucleoside/nucleotide analogs available clinically for treating CHB in China: tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV), which have significant antiviral effects, however, what are their influences on the long-term outcome of treating hepatitis B patients?

According to a recent study on health outcomes using TAF, TDF, or ETV for the treatment of 100,000 CHB patients in China, the 5-year and 10-year liver complication risks of patients treated with TAF would be lower than those treated with ETV or TDF.

Details of the study

Researchers constructed the health outcome model using an independent patient simulation framework. The model input was from randomized controlled trials and peer-reviewed Chinese literature and verified by a Chinese hepatologist group. 90% of the cohort composition was assumed as treatment-experienced (TE) hepatitis B patients, and 27% thereof had used lamivudine. According to REVEAL score and in combination with early alanine transaminase (ALT) normalization, 5-year and 10-year liver cirrhosis and hepatocellular carcinoma risks were calculated.

According to the model prediction, the 5-year and 10-year liver complication (including compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma) risks of patients treated with TAF would be lower than patients treated with TDF and patients treated with ETV.

In particular, the 5-year hepatocellular carcinoma risk of patients treated with TAF would be separately 13% and 31% lower than those treated with TDF and those treated with ETV.

Conclusion: The predicted 5-year and 10-year liver complication incidences of patients treated with TAF would be lower than those treated with TDF and those treated with ETV.

CHB drugs approved in China

CHB is one of the global major public health issues. TAF has been approved by the National Medical Products Administration of China (NMPA) on Nov. 8, 2018 to treat the CHB in adults and adolescents aged above 12 with a weight of at least 35kg. With this, there have been many CHB drugs approved for clinical use in China, including lamivudine (LAM) approved in 1998, ETV and adefovir dipivoxil (ADV) approved in 2005, PEG-interferon approved in 2006, telbivudine (LdT) approved in 2007, and TDF approved in 2013. If you want to get more information on CHB drugs, Pharmasource would be your best choice.

Advantages of TAF

1. Directly "targeting" the liver, with lower side effects

With the deepening of clinical studies, the time to market of new drugs is shorter than and the efficacy thereof is superior to drugs marketed earlier. Compared to TDF, TAF’s clinical dosage is 10 times less, and after it is administered, the average exposure of plasma tenofovir (TFV) in systemic plasma is 89% lower, which reduces the body toxicity. According to an in vitro test, the concentration of tenofovir-diphosphate (TFV-DP) produced by TAF in human primary hepatocytes is 5 times that by TDF. TAF directly "targets" the liver to further improve the antiviral efficacy.

2. Drug resistance not easily occurring

Study 108 and Study 110 are two global multicenter Phase III registered clinical studies on TAF, involving 1,632 previously untreated and treated adult HBeAg-negative and HBeAg-positive HBV patients, and 105 study centers from 17 countries and regions participated in those two randomized, double-blind, multicenter non-inferiority studies. Synthesizing results of the two studies, TAF had powerful antiviral efficacy for HBeAg-positive patients, and HBV DNA inhibition of TAF by week 96 was similar to that of TDF.

Considering that virus evolution and variation will cause drug resistance, HBV treatment should select drugs with low or no drug resistance to achieve long-term antiviral treatment, block disease progression, and reduce liver cancer risks. The biggest issue with drugs marketed earlier is the easy occurrence of drug resistance. According to the study on TAF, no drug resistance was detected to TAF during the 96-week treatment.

Hepatitis B in a certain proportion of patients will develop into liver cirrhosis and liver cancer if they are not treated, therefore, the main therapeutic goal of CHB patients is very clear, namely, to prevent and reduce disease progression and block hepatitis B from progressing to liver cirrhosis and liver cancer, to thus improve patients’ life quality and prolong the survival time.

According to research, risks of hepatitis B turning into liver cirrhosis and liver cancer increase with the increase of HBV DNA viral load; after the antiviral treatment, risks of liver cirrhosis and liver cancer will significantly decrease with the decrease of the viral load, showing that effective antiviral treatments can reduce risks of hepatitis B patients in suffering from liver cirrhosis and liver cancer. The study mentioned above shows that the predicted 5-year and 10-year liver complication incidences of patients treated with TAF would be lower than those treated with TDF and those treated with ETV. Therefore, choosing TAF is more appropriate for CHB patients from the perspective of a better long-term outcome.

References:

1. Ying Han, Bin Wu, Ming Hu, et al. Projection of health outcomes over 5-year and 10-year period using tenofovir alafenamide (TAF) for the management of chronic hepatitis B (CHB) in China. APASL2019. Manila. Poster.679.

2. garwal K, Fung S, Seto WK, et al. A phase 3 study comparing tenofovir alafenamide (TAF) to tenofovir disoproxil fumarate (TDF) in patients with HBeAg-positive, chronic hepatitis B: efficacy and safety results at week 96 Journal of Hepatology 2017;66 (suppl

3. 1):S478. FIR-153.

About the Author:

Xiaobin

Xiaobin holds a Master's degree in Pharmacy and currently work as a public health control staff. Navigating through the intricate and complex data each day and feeling a sense of insignificance of herself. While being happy to witness the golden time of the development of Chinese bio-pharmaceutical industry. Hope to learn and improve together with everyone.

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