Experimental hepatitis B drug may offer ‘functional cure’ 

A first-of-its-kind drug for hepatitis B is allowing some patients to stop treatment without showing signs of the dangerous liver virus, in what is called a “functional cure”, researchers reported on Thursday.

In two international studies, about one in five patients given the experimental drug saw their virus reduced to levels low enough for the immune system to keep it in check.

“We have not had a treatment which has come to this level of cure,” Dr Seng Gee Lim of the National University Health System of Singapore, who helped lead the GSK-funded studies, told reporters before presenting the findings at a scientific meeting in Barcelona, Spain.

The data were also published on Thursday in the New England Journal of Medicine.

Chronic hepatitis B can cause liver cancer or liver failure, and kills about 1.1 million people around the world each year. Improvements to current lifelong therapy, which can be difficult to maintain or access in some countries, have been sought for decades.

The new findings “represent a major step”, Dr Anna Lok, a hepatitis expert at the University of Michigan who was not involved in the research, wrote in the journal. But she cautioned that more study is needed to determine how long that remission-like state lasts.

The drug is bepirovirsen, nicknamed “bepi”, and developed by GSK and Ionis Pharmaceuticals. It is under fast-track review by the US Food and Drug Administration, with a decision expected in October. Regulators in Japan, China and Europe are also considering the drug.

Hepatitis B is a serious liver infection spread through contact with blood or other bodily fluids, including during childbirth. A highly effective vaccine can prevent it. For those who are infected, many experience an “acute” illness that lasts several months. But for some — about 1.7 million people in the US and more than 250 million worldwide — it becomes chronic, gradually damaging the liver.

Standard treatments, including daily pills, reduce levels of the virus and prevent liver damage. But a true cure remains elusive because hepatitis B has an unusual ability to hide in the body, ready to rebound if therapy stops.

The new drug targets hepatitis B by binding to its genetic components, suppressing viral replication as well as a key protein, the “S” or surface protein, and stimulating the immune system, said GSK vice-president Melanie Paff.

The trials included 1,838 patients assigned to receive either a bepi injection or a placebo weekly for six months, in addition to their regular pills. If the virus was undetectable for six months after stopping the injections, they could also stop their regular medication. In about 20% of those receiving bepi, the virus remained undetectable for six more months after all treatment stopped — that “functional cure” — something not seen in patients given the placebo, the researchers reported.

Patients receiving bepi who began the study with lower levels of the S protein were slightly more likely to achieve a functional cure, Lim said. He is conducting further research to determine why only some patients respond.

As for how long the functional cure lasts, GSK has tracked a small number of patients from earlier-stage studies and found most were still doing well up to three years later, Paff said.

Lim said side effects included mild redness or pain at the injection site and a temporary rise in enzymes that can indicate liver stress.

Lok, the Michigan hepatitis expert, noted that the trials did not include patients with cirrhosis, high S protein levels or other complicating factors.

-AP