With the help of the revolutionary Hepatitis C drug Solvadi, Gilead has become the world’s top10 biopharmaceutical giant with a market value that exceeds Lilly and AstraZeneca. After Hepatitis C was cured, the larger Hepatitis B population became the next target for the pharmaceutical industry.
Unlike Hepatitis C, Hepatitis B has a prophylactic vaccine that can provide nearly 90% of the immune protection efficacy, but Hepatitis B patients are more difficult to treat than Hepatitis C. Currently approved hepatitis B treatment drugs are mainly interferon and nucleoside antiviral drugs used for many years, with large side effects and low cure. The patient must take long-term medication to achieve sustained viral suppression, thereby reducing the incidence of liver cirrhosis and liver cancer.
The statistics of the global hepatitis B drug development pipeline do not involve preventive vaccines, and only involve the promotion of HBV infection treatment drugs to the clinical stage.
The therapeutic strategies for hepatitis B can target both the host and the virus. Therefore, many targets have been developed for the treatment of HBV infection. For example, Hepatera’s Myrcludex B’s mechanism of action is mainly to prevent the virus from entering the host cell. Replicor’s REP 2139 and REP 2165 are mainly to inhibit the secretion of hepatitis B surface antigen (HBsAg).
Roche terminated its global cooperation with Inovio Pharmaceuticals on Hepatitis B immunotherapy INO-1800 on August 3. We must not think that Roche is determined to give up the research and development of hepatitis B drugs. In fact, giants such as Roche, Johnson & Johnson and Gilead are active participants in the development of hepatitis B drugs. However, the specific mechanisms of Roche’s three hepatitis B drugs RO6864018, RO7020322, and RG7834 have not yet been disclosed.
INO-1800, abandoned by Roche, is a DNA vaccine that produces strong T cell and antibody responses in a mouse model. Hepatitis B-specific T cells migrate and stay on the surface of the liver to eliminate HBV-infected liver cells without liver injury.
Gilead is the king of antiviral drug development. In the hepatitis B area, in addition to the listed Hepsera (Adefovir dipivoxil), Viread (Tenofovir disoproxil fumarate, TDF), and TAF which has submitted a listing application to FDA and EMA, Gilead was once placed in the market. Highly hopeful hepatitis B DNA vaccine GS-4774.
Developed in collaboration with Giliead and GlobeImmune, GS-4774 contains heat-inactivated yeast cells, highly expressed regions of HBsAg that can be expressed, hepatitis B core antigen (HBcAg), and hepatitis B protein (HBx), which induce HBV-specific Host T cell response. However, GS-4774 failed to reduce the primary endpoint of serum HBsAg levels in a phase II study, code-named GS-US-330-0101 in 2015.
GS-9620 is a small molecule Toll-like receptor 7 (TLR7) agonist that is capable of inducing an interferon response and producing extensive immune protection. Roche’s TLR7 agonist ANA773/RG7795 has completed phase II studies but has not continued to appear in its R&D pipeline since 2012.
Johnson & Johnson
Johnson & Johnson entered into an acquisition agreement with Novira in November last year to include the latter’s hepatitis B drug NVR 3-778 and a range of other antiviral drugs. NVR 3-778 can interfere with viral replication by attacking the capsid protein of HBV virus.
Shortly thereafter, Novira again obtained a pre-clinical new type of small molecular antibody from chinese pharmaceutical company Chia Tai Tian Qing with a US$ 225 million (approximately RMB 1.6 billion) down payment + miles + post-listing sales commission in January this year. HBV Viral Drugs Global Development Rights Outside China.
ARC-520 is an RNA interference (RNAi) therapy that uses Arrowhead’s unique Dynamic Polyconjugates delivery system to silence the expression of certain HBV viral proteins, preventing them from multiplying. ARC-520 is suitable for chronic hepatitis B patients with high levels of HBV cccDNA (covalently closed circular DNA).
In April of this year, Arrowhead announced the shocking data of a phase IIb clinical study of ARC-520. ARC-520 and Baraclude (entecavir) for treatment of refractory HBeAg-negative chronic hepatitis B patients reduced serum HBV DNA levels by 99.99. %.
ARC-521 is a supplement to ARC520, which acts on the transcription of HBV cccDNA and messenger RNA involving integrated viral DNA, and is suitable for chronic hepatitis B patients with lower HBV cccDNA levels. Arrowhead plans to conduct a single dose and multiple dose phase I/II clinical study of ARC-521 in healthy volunteers and HBV patients.