Arrowhead Research (ARWR) today announced that the FDA has cleared the company to initiate its phase 2b study of ARC-520. The drug ARC-520 is an RNAi compound specifically made to knock down the genes of the Hepatitis B Virus. This phase 2b trial will be a multi-dose trial but patients in the trial can only be dosed up to 1 mg/kg. The company now states that it is in the process of setting up sites and will begin recruiting patients about one month from now. In addition the company is working with other regulatory agencies outside the U.S. to begin phase 2b trials for ARC-520 in other countries. 

The phase 2b trial is known as Heparc-2004 and will enroll up to 12 patients in total. The patients in the study will be given ARC-520 and in addition will be maintained with entecavir or tenofovir therapy. Eight patients will receive 1 mg/kg of ARC-520 and the other 4 patients will receive a placebo compound. Patients in this trial will be followed for approximately 147 days in which time Arrowhead will evaluate the primary and secondary endpoints of the study. 

The primary endpoint of the Heparc-2004 study will be to evaluate the decline in hepatitis B surface antigens -- HBsAg -- using ARC-520 as compared to a placebo compound. The secondary endpoint will be determining the safety and tolerability of the ARC-520 1 mg/kg drug. Of course the primary endpoint determining efficacy is important but the secondary is very important as well - the reason being that the Heparc-2004 study, the phase 2a single dose study, and the multiple dose non-clinical trial study, will all be used to send the FDA the required data in an attempt to revive the higher multi-dose studies of ARC-520. 

Back in December 2014 Arrowhead had sent an IND to initiate a parallel design multiple-dose study. This study would have included patients being treated with 2 mg/kg and 4 mg/kg of ARC-520.  In January 2015 the FDA put a stop to the program because they wanted more safety data for human use of those higher doses. As mentioned above, those other trials will be key in allowing the FDA to release the clinical hold on the higher 2 mg/kg and 4 mg/kg doses. What the higher doses should do is increase the efficacy outcome of the trial, but first thing is first Arrowhead must prove that such higher doses are tolerable in humans.