ARC-520 is a novel, liver-targeted, small molecule interfering RNA (siRNA)-containing therapy developed by Arrowhea for the treatment of chronic hepatitis B virus infection. The goal is to reduce all HBV transcription by interfering with RNA. In HBV-infected chimpanzee and mouse models, we observed a reduction in viral particles and viral protein expression. Viral proteins (especially HBeAg and HBsAg) are associated with immune tolerance, persistent infection and disease progression. Therapies targeting viral proteins can reestablish host immunity and thus promote seroclearance of HBsAg. Currently in Phase II clinical development, ARC-520, which is administered as a once-monthly injection, has the potential to functionally cure Hepatitis B. Arrowhead Research is one step closer to obtaining a cure for hepatitis B infection, according to CEO Anzalone. The company recently released positive data for its experimental antiviral treatment. The hepatitis B virus is 100 times more potent than HIV, but it can be prevented with a vaccine, which has been available since 1982. However, the vaccine is ineffective for the 400 million people infected with chronic hepatitis B worldwide. In many cases, existing hepatitis B drugs do not completely cure the infection, but often suppress viral replication, forcing patients to take them for the rest of their lives. Arrowhead’s drug, ARC-520, disassembles various components of the hepatitis B virus, and data show that it reduces a key protein in the virus that causes disease by more than 90 percent in both previously treated and untreated patients. “I think our data shows that we’re disassembling multiple viral components, which no drug has been able to do in hepatitis B so far, so I think we have a clear competitive advantage,” Anzalone said in an interview. Analysts said the company posted “stunning” positive interim data for the highest dose of its therapeutic drug compared to the smaller dose data Arrowhead had previously reported. A single 4 mg/kg dose was able to achieve a 99% peak reduction (or 1.9log) in a key disease-causing viral protein, and the data showed that there could be an average 1.05log reduction in previously untreated patients. “We would expect that the 1-log threshold could be achieved with multiple doses, and in fact a single 4 mg/kg dose was a fantastic result,” Tenthoff said. The drug showed a favorable safety and tolerability profile, and the data suggest that the drug can substantially disrupt other viral functions. These results prompt us to focus not only on developing ARC-520 in combination with other therapeutic agents to achieve a functional cure, but also to pay special attention to developing it for use in previously untreated patients, Anzalone added. Arrowhead specializes in ribonucleic acid interference (RNAi) therapies, which have long been of interest to developers because they are designed to “silence” certain genes to limit the production of disease-causing proteins, but which have also witnessed frequent clinical failures. Meanwhile, existing drugs work by binding to these proteins and rendering them inactive. d Research is a step closer to obtaining a drug to cure hepatitis B infection, according to CEO Anzalone. The company recently released positive data on its experimental antiviral treatment drug. The hepatitis B virus is 100 times more potent than HIV, but it can be prevented with a vaccine, which has been available since 1982. However, the vaccine is ineffective for the 400 million people infected with chronic hepatitis B worldwide. In many cases, existing hepatitis B drugs do not completely cure the infection, but often suppress viral replication, forcing patients to take them for the rest of their lives. Arrowhead’s drug, ARC-520, disassembles various components of the hepatitis B virus, and data show that it reduces a key protein in the virus that causes disease by more than 90 percent in both previously treated and untreated patients. “I think our data shows that we’re disassembling multiple viral components, which no drug has been able to do in hepatitis B so far, so I think we have a clear competitive advantage,” Anzalone said in an interview. Analysts said the company posted “stunning” positive interim data for the highest dose of its therapeutic drug compared to the smaller dose data Arrowhead had previously reported. A single 4 mg/kg dose was able to achieve a 99% peak reduction (or 1.9log) in a key disease-causing viral protein, and the data showed that there could be an average 1.05log reduction in previously untreated patients. “We would expect that the 1-log threshold could be achieved with multiple doses, and in fact a single 4 mg/kg dose was a fantastic result,” Tenthoff said. The drug showed a favorable safety and tolerability profile, and the data suggest that the drug can substantially disrupt other viral functions. These results prompt us to focus not only on developing ARC-520 in combination with other therapeutic agents to achieve a functional cure, but also to pay special attention to developing it for use in previously untreated patients, Anzalone added. Arrowhead specializes in ribonucleic acid interference (RNAi) therapies, which have long been of interest to developers because they are designed to “silence” certain genes to limit the production of disease-causing proteins, but which have also witnessed frequent clinical failures. Meanwhile, existing drugs work by binding to these proteins and rendering them inactive.