Hansoh Pharma's Novel Anti-HBV Drug Tenofovir Amibufenamide Nears Approval with Smooth NDA Review Progress

Highly anticipated, China's first small-molecule innovative drug for hepatitis B and a next-generation tenofovir prodrug with a completely novel structure—Tenofovir amibufenamide—is poised for market launch. Recently, the website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) indicated that the marketing application review for Hansoh Pharma's Class 1 innovative drug "Tenofovir amibufenamide" is progressing smoothly. Industry experts predict it is expected to be approved in the first half of the year, meaning hepatitis B patients in China will gain access to the country's first oral innovative drug produced in China. This innovative anti-HBV therapy was developed by Hansoh Pharma over an eight-year period.

According to WHO data, there are approximately 257 million individuals with chronic HBV infection worldwide. In 2020, the prevalence of hepatitis B virus infection among children under five years of age in China fell to below 1%, successfully shedding the label of a high-endemic country for hepatitis B. However, the patient population remains substantial. It is estimated that the current HBsAg prevalence in China's general population is 5%–6%, representing approximately 70 million chronic HBV-infected individuals. The number of patients with chronic hepatitis B (CHB) is estimated at 20 to 30 million. Over the past decade, the annual number of new cases has averaged around 1 million, accounting for one-third of reported Class A and Class B infectious disease cases. Hepatitis B remains one of the infectious diseases with the highest incidence in China and continues to pose a severe public health challenge.

Currently, achieving a cure for chronic hepatitis B remains difficult, and the majority of patients still require long-term treatment. The annual incidence rate of cirrhosis in chronic hepatitis B patients without antiviral therapy is 2%–10%, while the annual incidence rate of hepatocellular carcinoma in patients with cirrhosis is 3%–6%. Clinically, approximately 80% of liver cancer cases are attributable to hepatitis B. According to expert analysis, the total DALYs burden of liver cancer in 2050 is projected to increase by 20.0% compared with 2017 [4]. It is therefore evident that the treatment of hepatitis B still has a long way to go.

Although there is currently no curative medication for chronic hepatitis B, pharmacological treatment can control viral replication, delay disease progression, improve patients' quality of life, and prolong survival. According to the recommendations of the *Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 Edition)*, the preferred first-line treatments for chronic hepatitis B are high-potency, low-resistance nucleos(t)ide analogues and pegylated interferon. The nucleos(t)ide analogues primarily include three drugs: tenofovir alafenamide, entecavir, and tenofovir disoproxil fumarate.

In the long-term treatment of hepatitis B, there is an urgent clinical need for anti-HBV drugs with high efficacy, a high barrier to resistance, and a low risk of bone and renal adverse events.

In October 2013, the development of tenofovir amibufenamide was officially initiated. Over the subsequent eight years, tenofovir amibufenamide underwent seven clinical studies. Among them, the pivotal Phase III clinical trial was designed as a multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group, non-inferiority study, enrolling a cumulative total of 1,002 patients. Conducted as a head-to-head clinical trial against the first-line hepatitis B treatment "tenofovir disoproxil fumarate," it is, to date, the Phase III clinical trial for a novel hepatitis B drug with the largest enrollment of Chinese patients.

As the latest second-generation prodrug of tenofovir (TFV), amtenofvir demonstrates a superior safety profile compared to tenofovir disoproxil fumarate through structural optimization. Its active metabolite, tenofovir diphosphate (TFV-DP), accumulates at high concentrations in the liver, thereby achieving hepatic targeting and enhancing drug utilization. Studies indicate that amtenofvir requires less than one-tenth the dose of tenofovir disoproxil fumarate to achieve comparable antiviral efficacy, while exerting a reduced impact on bone mineral density and renal function.

At the 2021 Annual Meeting of the Asian Pacific Association for the Study of the Liver (2021 APASL), researchers from Nanfang Hospital, Southern Medical University, jointly with Jiangsu Hansoh Pharmaceutical Group Company Limited (the operating entity of Hansoh Pharma), presented the 48-week results from a large-scale Phase III clinical trial of this drug conducted in patients with chronic hepatitis B (CHB) in China: ametenovofovir demonstrated efficacy comparable to tenofovir disoproxil fumarate (TDF) in adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B. Regarding key secondary safety endpoints (bone and renal parameters), ametenovofovir was significantly superior to TDF. The study results indicate that while ensuring robust anti-HBV efficacy, ametenovofovir exhibits a more favorable safety profile, making it an excellent choice for long-term therapy in adult patients with chronic hepatitis B.

For over two decades, Hansoh Pharma has consistently focused on unmet clinical needs, remained committed to innovation, continuously introduced high-quality innovative medicines, improved patients' quality of life, and reduced the medication burden.