Arrowhead Research Corporation ($ARWR) is looking to add another entrant into the clinical trial race to commercialize the first RNAi-based compound, a market category that could become a new class of drugs akin to monoclonal antibodies and produce revenues exceeding $1 billion by 2020, according to one projection.
The company recently announced that it has submitted its Investigational New Drug application for its RNAi candidate, ARC-520, for the treatment of the chronic hepatitis B virus.
If the application is approved, two Phase IIb human clinical trials will primarily test the extent of B surface antigen decline compared to placebo after ARC-520 injection in combination with the standard drugs entecavir or tenofovir, the release says. One trial will test patients who are negative for hepatitis B e-antigen (HBeAg), and the other those who are positive for HBeAg.
"As with our recent application to begin a Phase 1 study with ARC-AAT, this IND represents achievement of a key 2014 goal," said Arrowhead CEO, Dr. Christopher Anzalone in a statement. "We look forward to beginning multi-dose studies with ARC-520."
The candidate uses Arrowhead's dynamic polyconjugates delivery system, whereby small interfering RNA is carried by nanoparticles that are designed to have properties similar to viruses.
The nanoparticles contain a targeting ligand that guides them to the targeted cell, which they enter via an endosome. A change in pH within the endosome causes it to break down. Then the siRNA frees itself from the nanoparticle carrier, and enters the cytoplasm, where it associates with the RNA induced silencing complex and cleaves messenger RNA, resulting in the silencing of genes associated with the disease, in this case hepatitis B, the Arrowhead website explains.
The company claims this polymer-based delivery method is superior to lipid-based systems. Employees surely hope that is the case, for the company reported a loss of nearly $60 million in fiscal year 2014; R&D expenses nearly tripled in to $23.1 million, meaning the losses could result in riches in the years ahead, but only if the FDA waves the checkered flag and agrees that the RNAi candidates, like ARC-520 are safe and efficacious.
There are three other RNAi candidates in the pipeline, according to the Arrowhead website. Meanwhile fellow RNAi specialist Alnylam ($ALNY) has its own hepatitis B candidate, but it is in the pre-clinical stage.