cross-licensing deal in 2012 in which Alnylam licensed its RNAi chemistry technology for hepatitis B to Arrowhead—that’s what ARC-520 is based around—and Arrowhead licensed its dynamic polyconjugates delivery technology to Alnylam, which it can use for a disease target that has yet to be disclosed, Anzalone says.
Biotech is “full of stories of competitors collaborating on some drugs and competing on other drugs. That just is going to happen,” Anzalone says. Arrowhead is focused on getting its hepatitis B drug to market as quickly as possible, and he notes that it entered clinical trials in mid-2013, while Alnylam won’t enter the clinic until 2016. “We’ll have a substantial lead on them,” Anzalone says. “We also just need to make sure that we have a better drug.”
More companies are trying to develop hepatitis B treatments in part because a flurry of hepatitis C treatments have been approved in the past three years that, in tandem with earlier approved drugs, effectively cure that disease. Those new treatments include Gilead’s sofosbuvir (Sovaldi), Gilead’s combined sofosbuvir and ledipasvir (Harvoni), Janssen Therapeutics’ simeprevir (Olysio), and Merck’s boceprevir (Victrelis). Now, some companies have set their sights on hepatitis B.
About 350 million people worldwide suffer from chronic hepatitis B—more than double those who suffer from chronic hepatitis C. So, why did hepatitis C get “solved” first?
Turns out, the two diseases manifest themselves in completely different ways, and hepatitis B has proven to be a more difficult nut to crack than hepatitis C, London says. The hepatitis B virus lodges itself in the DNA of liver cells, which complicates things. Hepatitis C, meanwhile, replicates itself in the cytoplasm of cells, rather than in the nucleus. “It is more accessible to drugs, and that’s what’s turned things around,” London explains.
Currently, typical hepatitis B treatment involves drugs, like entecavir and tenofovir, that prevent the existing copies of virus from replicating, but don’t eradicate them, so patients have to take the medications for the rest of their lives, London says. And even with antiviral treatment, the patients still have a heightened risk of developing cirrhosis of the liver and cancer, Anzalone says.
For his part, London thinks RNAi is an “interesting” technology that could be useful in fighting hepatitis B, but he’s doubtful it holds the answer to defeating the virus for a variety of reasons related to the biology of the virus and the way it hides out in the liver cells it infects. “If it happened, it’d be wonderful,” he says, “but I just am skeptical.”
