Vir Biotechnology has started a phase 1/2 trial of its gene-silencing drug for hepatitis B virus (HBV), the first clinical candidate from its partnership with Alnylam Pharmaceuticals.
The study of VIR-2218 will enroll about 100 healthy volunteers and patients with chronic HBV infection and will test a subcutaneous injection of the drug, which is designed to inhibit expression of all HBV proteins including hepatitis B surface antigen (HBsAg) and to help patients' immune systems respond to the infection. It is due to read out in 2019.
The closest RNAi rivals to VIR-2218 are Arrowhead Pharmaceuticals' ARO-HBV and Arbutus Biopharma’s ARB-1467, both of which are in midstage testing. Arrowhead’s program has drawn the attention of a big partner in the shape of Johnson & Johnson, which paid $175 million upfront for global rights a few weeks ago. Meanwhile, Arbutus has the backing of Vivek Ramaswamy’s Roivant for its program.
VIR-2218 was known as ALN-HBV-02 before Alnylam licensed it to Vir last year in an infectious disease collaboration valued at up to $1 billion and is the first of the partnered programs to start clinical testing. Vir CEO George Scangos, who previously headed Biogen, said the trial “marks our transition to a clinical-stage company.”
Despite the availability of a vaccine against HBV, more than 290 million people worldwide are chronically infected with the virus and it kills about 900,000 of them each year.
There are drug treatments available such as Roche’s Pegasys (peginterferon alfa-2a), which has to be given by injection for 48 weeks and can have severe side effects, and oral antiviral medicines such as tenofovir and entecavir. None of these options can clear HBV from cells however, achieving a cure in just 3% of cases, so some patients require lifelong treatment to control the infection.
People chronically infected with HBV are still at a higher risk of developing liver cirrhosis and liver cancer, so there is a real need for additional treatments that could potentially achieve a cure and eradicate the virus from the body—as has been achieved so successfully with hepatitis C virus.
“What we need is a new treatment that can cure HBV and remove the need for lifelong treatment,” said hepatologist Ed Gane, M.D., of the University of Auckland School of Medicine in New Zealand.
“The initiation of clinical testing of this new treatment is an exciting step forward in the pursuit of a functional cure for this disease.”
Other approaches to HBV coming through the pipeline include Transgene’s immunotherapy TG1050, which is based on three HBV antigens and showed evidence of safety and efficacy in a phase 1 trial, as well as various small-molecule drug candidates from the likes of GlaxoSmithKline and Ionis Pharmaceuticals, Spring Bank Pharma, Gilead Sciences, Enyo Pharma and Replicor.
Earlier this year, analysts at William Blair said the market for an HBV cure could be similar in size to that for HCV, which saw multibillion-dollar sales for a few years before starting to shrink as the eligible patient pool began to dry up. They predicted potential cumulative sales of about $200 billion over two decades, adding that potential is likely to drive consolidation among HBV players over the next five years.