Chronic hepatitis B infection is currently managed with antiviral drugs that patients must take long-term, perhaps for life. The FDA has approved a new GSK drug that offers the potential for a six-month course of treatment and then nothing more.
For these patients, the drug is able to knock the virus down to a level where the immune system regains control and keeps the infection in check — a functional cure. The FDA’s Tuesday regulatory decision brings a new product to GSK’s infectious disease portfolio, one offering a first-in-class approach expected to generate blockbuster sales. Known in development as bepirovirsen, GSK will market this drug under the brand name Hibsago.
While hepatitis B virus can lead to an acute infection, it becomes chronic when the immune system is unable to clear the virus. An estimated 1.7 million people have chronic hepatitis B infection, which is associated with higher rates of liver cancer and death from all causes. Standard treatment is a chronic antiviral therapy that either inhibits viral DNA or stimulates an immune response against the virus. These drugs achieve low rates of functional cure, where signs of the virus can no longer be detected in the blood.
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Hibsago works differently than the older antivirals. This new GSK drug is an antisense oligonucleotide designed to degrade the messenger RNA for hepatitis B virus, which in turn reduces levels of the virus’s DNA and viral proteins to a point where a patient’s immune system can regain control. Achieving a durable and sustained response could result in a functional cure.
The regulatory submission for Hibsago was based on two placebo-controlled Phase 3 studies that evaluated the study drug, administered as a weekly injection, for up to 24 weeks. Participants in the trial were able to continue taking a standard of care hepatitis B antiviral medicine during the treatment period. During this period, patients who met certain lab and health test requirements were permitted to stop taking the existing antiviral.
Across both studies, results showed 24% of patients who received Hibsago met requirements for stopping their existing medicine compared to none in the placebo arm. At 24 weeks after stopping all hepatitis B treatment, 19% of patients in the Hibsago arm had the virus under control. Also, a protein that signals hepatitis B infection could not be detected in their blood. Detailed results were presented in May during the European Association for the Study of the Liver (EASL) annual meeting and simultaneously published in the New England Journal of Medicine.
The most common adverse reactions reported included injection site reactions, fever, and fatigue. Results also showed some patients had elevated levels of liver enzymes. A black box warning on Hibsago’s label instructs clinicians to conduct liver enzyme tests prior to starting treatment and periodically during the treatment period. The warning also flags a potential reduction in blood platelet levels that raises the risk of life-threatening bleeding.
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The regulatory decision permits use of Hibsago in patients without liver cirrhosis. These patients must have been receiving antiviral therapy for at least six months to suppress levels of hepatitis B viral DNA. Eligible patients must also have hepatitis B surface antigen levels below a specified threshold, which is determined by a companion diagnostic. The FDA has authorized a Roche test to select patients for treatment with Hibsago.
“Despite current therapies, many people living with chronic hepatitis B remain on treatment indefinitely and continue to face the risk of serious liver complications,” GSK Chief Scientific Officer Tony Wood said in a prepared statement. “For the first time, with Hibsago, U.S. patients have the potential to achieve functional cure after a six-month treatment course, with the added convenience of the option of self-administration after the first dose.”
After the EASL presentation of Hibsago’s Phase 3 data in May, analysts at William Blair said they expected broad uptake of the drug. They noted that the current chronic hepatitis B market is worth $2.5 billion annually and the total addressable market is projected to grow to more than $7 billion by 2035. Leerink Partners said Hibsago offers blockbuster sales potential, but the bank cautioned that this drug’s uptake could be gradual given the testing and monitoring requirements for the therapy.
Hibsago came from the labs of Ionis Pharmaceuticals, a specialist in antisense oligonucleotide drugs. Ionis and GSK began an infectious disease drug R&D alliance in 2010. GSK licensed the hepatitis B program from Ionis in 2019. Ionis is eligible receive milestone payments tied to the regulatory and commercial progress of the drug; the total payout could top $510 million, not including royalties from GSK’s sales of the new product.
Hibsago was first approved in August in Japan. The drug is also currently under regulatory review in China.
Illustration: libre de droit, via Getty Images