Chronic hepatitis B (CHB) is a major global public health challenge caused by persistent infection with the hepatitis B virus (HBV). If not effectively controlled, it may progress to severe complications such as liver cirrhosis and hepatocellular carcinoma, posing a serious threat to patients’ health and survival. In the ongoing development of anti-HBV therapies, Tenofovir Amibufenamide (Chinese generic name: Aimitinofovir; brand name: Hengmu®), a novel nucleotide reverse transcriptase inhibitor independently developed in China, has brought new hope to patients with chronic hepatitis B through its unique structural advantages and outstanding clinical performance.
I. Basic Characteristics and Development Background
Tenofovir Amibufenamide is a phosphonamidate prodrug of tenofovir and is classified as a prescription medication. It was independently developed by Jiangsu Hansoh Pharmaceutical Group Co., Ltd., with full proprietary intellectual property rights. The development process spanned eight years, from project initiation to clinical research, demonstrating the technical capabilities of China’s innovative drug R&D ecosystem.
In June 2021, Tenofovir Amibufenamide was approved for marketing by the National Medical Products Administration (NMPA). In December of the same year, it was included in the National Reimbursement Drug List (NRDL), significantly improving accessibility and enabling more patients with chronic hepatitis B to benefit from this innovative therapy.
II. Core Mechanism of Action
As a nucleotide reverse transcriptase inhibitor, the antiviral activity of Tenofovir Amibufenamide centers on the inhibition of HBV replication, with enhanced liver targeting achieved through structural optimization. Compared with traditional tenofovir formulations, its key advantages include higher cell membrane permeability, enabling more efficient entry into hepatocytes, improved plasma stability, and reduced systemic exposure to tenofovir (TFV). These properties enhance antiviral efficacy while minimizing systemic adverse effects.
The mechanism of action can be summarized in three key steps:
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After oral administration, Tenofovir Amibufenamide is absorbed as a prodrug and primarily hydrolyzed within hepatocytes to tenofovir.
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Tenofovir is subsequently phosphorylated by intracellular kinases to form the pharmacologically active metabolite, tenofovir diphosphate (TFV-DP).
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TFV-DP is incorporated into viral DNA by HBV reverse transcriptase, resulting in chain termination and potent inhibition of viral DNA synthesis.
Importantly, in vitro studies have shown that TFV-DP exhibits weak inhibitory effects on mammalian DNA polymerases, including mitochondrial DNA polymerase γ, indicating no significant mitochondrial toxicity and supporting its safety for long-term use.
III. Clinical Application Value
(1) Indications and Dosage
Tenofovir Amibufenamide is indicated for the treatment of adult patients with chronic hepatitis B. According to the prescribing information, the recommended dosage is one tablet (25 mg) once daily, administered orally with food. Studies have demonstrated that administration with a high-fat meal increases drug absorption, bioavailability, and therapeutic efficacy compared with fasting administration.
If a dose is missed and remembered within 18 hours of the scheduled dosing time, one tablet should be taken as soon as possible and the regular dosing schedule resumed. If more than 18 hours have passed, the missed dose should be skipped and the next dose taken at the regular time. If vomiting occurs within 1 hour after dosing, an additional tablet should be taken; if vomiting occurs after more than 1 hour, no additional dose is required.
(2) Clinical Efficacy Advantages
Multiple clinical studies and real-world data have confirmed the potent antiviral efficacy of Tenofovir Amibufenamide. Compared with the conventional first-line agent tenofovir disoproxil fumarate (TDF), Tenofovir Amibufenamide achieves comparable antiviral effects at less than one-tenth of the dose, with efficacy similar to other first-line anti-HBV agents.
In a multicenter, prospective real-world study involving 183 patients with chronic hepatitis B, the virological response rate (HBV DNA <100 IU/mL) with Tenofovir Amibufenamide was comparable to that of TDF. Among treatment-experienced patients who switched from other antiviral regimens to Tenofovir Amibufenamide, antiviral efficacy was maintained.
Another retrospective real-world study compared Tenofovir Amibufenamide with tenofovir alafenamide (TAF). At week 24, treatment-naïve patients in the Tenofovir Amibufenamide group achieved a significantly higher virological response rate (92%) than those in the TAF group (74%). Among treatment-experienced patients, no statistically significant difference in virological response was observed between the two groups. Both groups demonstrated high rates of alanine aminotransferase (ALT) normalization, indicating effective improvement of hepatic inflammation alongside viral suppression.
IV. Safety Profile and Precautions
(1) Key Safety Advantages
The most prominent advantage of Tenofovir Amibufenamide lies in its excellent bone and renal safety profile. Long-term use of traditional tenofovir formulations (such as TDF) has been associated with decreased bone mineral density and renal impairment. By reducing systemic exposure to tenofovir, Tenofovir Amibufenamide significantly lowers the risk of adverse effects on bone metabolism and renal function.
Clinical studies have shown decreases in serum creatinine levels and improvements in estimated glomerular filtration rate (eGFR) in patients receiving long-term Tenofovir Amibufenamide therapy, without evidence of clinically significant bone density loss. Furthermore, a 144-week long-term study demonstrated stabilization of lipid profiles after switching from TDF to Tenofovir Amibufenamide, with no notable lipid abnormalities.
(2) Potential Adverse Reactions and Special Population Considerations
Although Tenofovir Amibufenamide has a favorable safety profile, potential adverse reactions may occur, primarily including gastrointestinal symptoms such as nausea, vomiting, decreased appetite, abdominal pain, and abdominal distension. Some studies suggest a slightly higher incidence of dyslipidemia compared with TDF (11.4%); therefore, lipid levels should be monitored every 6–12 months during long-term therapy.
Regarding special populations, safety and efficacy data are currently lacking for patients under 18 years of age and for those aged 65 years and older; caution is advised in these groups. Pregnant and lactating women should use the drug with particular caution and only under medical supervision. In patients with renal impairment (estimated creatinine clearance <50 mL/min) or severe hepatic impairment, safety and efficacy have not been established, and routine use is not recommended.
V. Research Progress and Clinical Significance
As the first China-developed oral anti-HBV innovative drug, the approval of Tenofovir Amibufenamide not only fills a gap in domestically developed oral HBV therapies but also breaks the long-standing dominance of imported drugs in this field, advancing the localization and independence of China’s hepatitis B drug development.
In recent years, an increasing number of real-world studies have further validated its efficacy and safety across broader patient populations, providing robust evidence for clinical use. For example, real-world data presented at the 2024 European Association for the Study of the Liver (EASL) Annual Meeting once again confirmed efficacy comparable to TDF and superior renal safety, laying the groundwork for wider global adoption.
From a clinical perspective, Tenofovir Amibufenamide offers a low-dose, highly effective, and safe treatment option for adult patients with chronic hepatitis B, particularly those requiring long-term therapy and those at risk for bone or renal complications. Inclusion in the National Reimbursement Drug List has substantially reduced the financial burden on patients and improved access to treatment, contributing meaningfully to improved overall CHB management and reduced risks of cirrhosis and liver cancer in China.
VI. Conclusion
Tenofovir Amibufenamide, a novel second-generation tenofovir agent independently developed in China, achieves efficient liver-targeted antiviral activity through structural optimization. With confirmed efficacy, excellent bone and renal safety, and convenient dosing, it represents an optimal therapeutic choice for adult patients with chronic hepatitis B, particularly those requiring long-term antiviral treatment. As further long-term real-world evidence and clinical experience accumulate, Tenofovir Amibufenamide is expected to play an increasingly important role in the global management of chronic hepatitis B, contributing Chinese innovation to the achievement of worldwide hepatitis B control goals.
Written by DengyueMed
