Current Situation and Prospect of Arrowhead (ARWR) and Its Hepatitis B siRNA Drugs

In August 2018, Onpattro (Patisiran), developed by Alnylam Pharmaceutical Company, announced FDA approval for adult patients with peripheral neuropathy (polyneuropathy) caused by hereditary transthyroxine amyloidosis (hATTR). This is the first small interfering RNA (siRNA) drug approved by the FDA. Because of its small population, it does not seem to have brought about a significant increase in the company's share price, but it has pushed the long-silent research and development of siRNA back to the public's horizon, especially the highly focused treatment of hepatitis B.

1. Current clinical treatment of hepatitis B

At present, antiviral therapy mainly focuses on interferon-alpha (IFN-alpha) and five nucleoside (acid) analogues (lamivudine, adefovir dipivoxil, entecavir, telbivudine and tenofovir). (1) IFN is the first anti-HBV drug approved by FDA. It mainly eliminates the virus by direct antiviral effect and inducing immune response. However, because of its low response rate, many side effects, high price and limited treatment targets, it is restricted. (2) The common feature of nucleoside (acid) analogues in anti-HBV is that they specifically act on viral polymerase and have a strong effect of inhibiting viral replication. Patients are more tolerant to drugs than interferon. However, with the extensive and long-term use of nucleoside (acid) drugs, DNA polymerase mutation can be induced to form drug resistance, leading to the emergence of drug-resistant strains, making the treatment far from achieving the desired effect. At present, it is difficult to cure hepatitis B by virus polymerase.

2. RNAi Technology and Layout of R&D Companies in the Field

Currently, the research and development of new drugs for HBV includes the whole life cycle of HBV replication: involving the whole process of HBV cell entry, the production and processing of HBV CC DNA, the replication and expression of viral genes and the expression of viral proteins.

RNA interference (RNA interference) is a kind of inhibiting HBV gene expression. RNA interference is a phenomenon that causes specific degradation of target RNA by small interfering RNA (siRNA) to silence genes after transcription. This phenomenon widely exists in nature, is an ancient and important protection mechanism, is a mechanism to resist the invasion of foreign genes in the evolution of organisms, and plays an important role in stabilizing the genome. As RNAi can be used as a simple and effective genetic tool to replace gene deletion, it is setting off a real revolution in the field of functional genomics and will accelerate the pace of research in this field. In short, RNAi therapy is to enable siRNA to enter cells, interfere with the function of specific disease gene RNA, and stop the translation of proteins to play a role in disease treatment.

Alnylam (ARCT), Arbutus (ABUS), Arrowhead (ARWR) and Arcturus (ARCT) all have their own layout in this field. Among them, Arowhead, who once led the industry and whose share price had risen and fallen sharply, has attracted much attention.

Three. Arrow

Arrowhead Pharmaceuticals (previously arrowhead research corp) is a listed company specializing in nanotechnology (arwr). The company's current R&D pipeline is as follows:

ARC-520, once the core product, is a drug based on RNA interference for the treatment of chronic hepatitis B. In order to be the earliest new RNA drug to enter Phase II clinic, Arrowhead's exclusive technology EX1 was adopted, which has the potential of functional cure of hepatitis B. However, the research and development process of the drug was not smooth, and it was restarted after the suspension of clinical research. However, in November 2016, due to the death of non-human primates, the research was finally terminated, and the stock price dropped by 60%. Compared with the clinical trials of the drug in human body, it is safer.