As a drug developer, in recent years, the development of first-class viruses into the development of inhibitors has been booming, of which Gilead Sciences' Hepcludex (bulevirtide) for HDV infection has been listed in Europe and is expected to be launched in the United States this year.
Hepatitis D innovative drug bulevirtide, listed in Europe, what enlightenment to R & D personnel?
Patients with chronic hepatitis D infection (CHD) co-infected with HBV and HDV have a significantly higher risk of progressing to cirrhosis and hepatocellular carcinoma than single HBV infection. CHD is persistently present by HDV, a single-stranded RNA virus that relies on HBV for replication and cladding, and the envelope of HDV consists of small, medium, and large forms of hepatitis B surface antigen or HBV surface protein (HBsAg).
Although nucleoside (acid) analogues (NAs) (such as tenofovir fumarate (TAF)) have been used worldwide to effectively control chronic hepatitis B, this approach is ineffective against CHD. Peginterferon α (PEG-IFNα) may cause a sustained virological response to some CHDs, but PEG-IFNα may be associated with major side effects.
As a result, we will see that many new drug developers around the world are already committed to providing effective and safe treatment options for CHD patients! The HBV/HDV hepatocyte entry inhibitor bulevirtide has pioneered in this regard, having received conditional approval from the European Medicines Agency (EMA) in July 2020 at a dose of 2 mg/day for the treatment of adult patients with CHD and compensatory liver disease.
bulevirtide is a subcutaneously injected synthetic preS1 lipopeptide that competes with the pre-S1 domain of HBsAg to bind to NTCP on the surface of hepatocytes. The published Phase 2 clinical trials MYR202 and MYR203 studies evaluated the safety and efficacy of bulevirtide in different doses and in combination or without TDF (MYR202) or PEG-IFNα (MYR203).
The results showed that after 24 weeks of treatment, the bulevirtide + TDF combination showed that it could induce bulevirtide dose-dependent inhibition of HDVRNA in up to 60% of CHD subjects and normalize elevated ALT levels in up to 50% of CHD. Bulevirtide is well tolerated, and asymptomatic elevation of serum bile acids is the most common adverse event.
In the MYR203 study, the researchers extended the treatment to 48 weeks and improved antiviral and biochemical efficacy in combination with the bulevirtide + PEG-IFNα combination and at the expense of PEG-IFNα side effects. It is worth noting that the decrease in hepatitis B surface antigen levels only occurred in the MYR203 study (bulevirtide + PEG-IFNα combination)! The hepatitis B surface antigen remained positive for all subjects in the MYR202 study (bulevirtide + TDF combination), and HDVRNA recurrence occurred after 93%-97% of the subjects used bulevirtide and stopped.
Currently, clinical trials of MYR204 (Phase 2) and MYR301 (Phase 3) are being evaluated for the use of bulevirtide over a longer period of time (with or without PEG-IFNα) (trial data and conclusions are from Gilead and MYR companies that have been acquired by Gilead).
Xiaofan Health Conclusion: Although the enthusiasm of global R&D personnel to develop HBV/HDV into inhibitors is currently high, this new direction has only achieved scientific research results in HDV, that is, Gilead's HDV drug bulevirtide, but its impact on HBsAg is limited, and the prospect of innovative drugs in hepatitis B is not clear.
Although bulevirtide has been listed in Europe, the actual experience and post-marketing clinical data on the use of bulevirtide are still scarce. This new target has attracted the attention of foreign researchers, and there is no candidate drug of the same target in China, including hiprapeptide (Phase 2), HH-003 (just entered Phase 2), in the future, I believe that there may be more R & D personnel in China to devote themselves to the development of inhibitors this novel direction.
Virus entry inhibitors have so far been mainly manifested in the development prospects of drugs in the direction of HDV, but in the past, even Gilead's first subcutaneous injection of bulevirtide also has the convenience of drug delivery needs to be improved, and clinical-stage biotechnology company Assembly Biosciences is developing a full oral ABI-XXX (a new type of HBV/HDV into the inhibitor, early stages);
Either there are no effective drugs in the hepatitis D field, or a large number of new targets have suddenly appeared, and in recent years, in addition to the virus entering the inhibitor, there are several new targets that have also shown promise in drug development in HDV.
The above is a new hepatitis D drug, developed by the German MYR pharmaceutical company acquired by Gilead Sciences, and is not a new drug for hepatitis B that has been listed, and its clinical research on hepatitis B has not been disclosed more. The medical technology information here is that Xiaofan Health summarizes the development progress of hepatitis B innovative drugs in the preclinical and clinical research stages around the world, which is convenient for readers to query and obtain, and timely grasp the development progress in this regard.
At the same time, it also allows researchers and clinical researchers in this field to learn the views and professional knowledge of the frontiers of the industry, and easily obtain medical information such as drug targets, mechanisms of action, novel chemical structures and pre-clinical or clinical research data of related compounds, which are usually noted in the text with screenshots or text, and readers and friends can also verify.
In addition, the science popularization here is the whole process of new drug development, and the research and development of new drugs should follow scientific laws and cannot be rushed to make quick profits. Preclinical studies and clinical trials are done to evaluate the safety and efficacy of drugs, and can only be marketed after successful completion of phases I, II and III. Most of the new hepatitis B drugs under research introduced by Xiaofan Health are in the research stage, and I hope that readers will understand. Here only popular science drug development and development of drugs, not how to popularize drugs. Trial data and research progress are also derived from information that has been published in medical journals or pharmaceutical companies, and it is also known that biopharmaceutical personnel and clinical researchers around the world are actively working hard to solve problems. However, there are many uncertainties in the development of new drugs, before the trial data comes out, the sponsors and researchers do not know the results, therefore, it is impossible to give a specific timetable for the listing of new drugs, I hope to understand more about the pharmaceutical personnel and pilot medical staff responsible for the whole process of new drug development, thank you.