With the FDA’s green light in hepatitis B, GSK and its Ionis-licensed medicine bepirovirsen have racked up several notable distinctions, bringing the antisense oligonucleotide class to bear against the virus for the first time alongside the promise of functional cure-standard efficacy versus pre-existing treatments.
Late Tuesday, the FDA gave the go-ahead to bepirovirsen to treat chronic hepatitis B (CHB) virus infection in tandem with nucleos(t)ide analogue reverse transcriptase inhibitor (Nrtl) therapy in adults without cirrhosis. The drug will now carry the commercial moniker Hibsago and is specifically indicated in those who’ve already been taking Nrtl therapy for at least six months, and who have suppressed hepatitis B virus DNA and virus surface antigen levels no greater than 3000 IU/ml.
GSK contends that the approval—delivered via FDA priority review and breakthrough therapy status—came in part through the recognition that its new hepatitis B treatment combo significantly ups the ante over standard-of-care nucleos(t)ide analogues, which include drugs like Bristol Myers Squibb’s Baraclude and Gilead Sciences’ Viread.
That class of treatments can block the hepatitis B virus’ ability to replicate, cutting down viral numbers, but its potential to deliver a functional cure, which refers to the reduction of viral DNA and proteins to undetectable levels, is limited.
“Despite current therapies, many people living with chronic hepatitis B remain on treatment indefinitely and continue to face the risk of serious liver complications,” Tony Wood, GSK’s chief scientific officer, said in a statement. “For the first time, with Hibsago, US 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.”
In its own approval announcement on Oct. 20, the FDA hailed Hibsago as a “first-of-its-kind” treatment in chronic hepatitis B, with the acting director of CDER’s Office of Infectious Diseases, Wendy Carter, adding that the approval “represents an important advance for people living with this serious disease.”
The take was much the same among analysts at Jefferies, who wrote to clients Wednesday that the FDA check mark "validates the functional-cure opportunity," while caveating that safety and monitoring considerations may "cause debate" and make the drug's trajectory less certain in the real world.
Chronic hepatitis B is a long-term liver infection caused by the hepatitis B virus (HBV) that, over time, can lead to serious liver disease, including cirrhosis, and raise the risk of liver cancer.
Hibsago, for its part, is designed to target the genetic instructions the hepatitis B virus uses to replicate and make viral proteins, ultimately curbing the overall amount of the virus and surface antigens in the body.
GSK got its hands on the drug by way of a 2019 pact with Ionis Pharmaceuticals, with bepirovirsen becoming the recent centerpiece of a busy HBV pipeline after GSK last year shifted focus away from another functional cure candidate coded GSK3528869.
Hibsago should be made available to U.S. patients before the end of the year, a GSK spokesperson told Fierce, adding that the drug’s list price will become public once pricing and reimbursement discussions have wrapped with payers.
“We price our medicines according to the value and outcomes they bring to patients, providers and payers while being sensitive to current market and societal expectations,” the spokesperson said, flagging Hibsago’s functional cure-like efficacy and the fact that the price will reflect the medicine’s “significant clinical value.”
The company will also be leveraging access and patient support programs to assist with Hibsago’s U.S. rollout.
The FDA signed off on the drug after reviewing data from a pair of late-stage trials, B-Well 1 and B-Well 2, which each met their primary endpoint when Hibsago was tied to a statistically significant improvement in functional cure versus placebo in the overall study population.
In detailed data from the program posted earlier this year, GSK said Hibsago allowed 19% of patients from that broad population to achieve its strictly defined functional cure criteria, which in the context of the studies was defined as hepatitis B surface antigen (HBsAg) loss and undetectable HBV DNA for at least 24 weeks after the treatment.
For the subgroup of patients with HBV surface antigen below the 1,000 internal units per milliliter threshold at the trial’s start, the functional cure rate rose to 26%.
With Hibsago's label confirmed to currently focus on patients already on therapy, as the Jefferies team predicted, the analysts said they continue to expect the drug to reach potential peak sales of 2.2 billion pounds sterling (around $2.95 billion).
On safety and tolerability, meanwhile, GSK noted that Hibsago’s report card in its studies was “acceptable,” citing injection site redness, local pain and a “temporary rise in the blood level of a liver enzyme” as the most commonly recorded side effects.
The drug will carry a boxed warning for serious liver reactions and low platelet counts, which can raise the risk of potentially fatal bleeding, the FDA noted in its approval announcement. Hibsago also carries warnings for worsening kidney function and serious inflammatory adverse reactions like vasculitis, plus the potential for other risks if the injection isn’t administered correctly.
Patients will need regular blood tests and doctor follow-up before and during treatment to monitor for risks and side effects, the FDA added.
That boxed warning, and monitoring requirements that the Jefferies team called "intensive" will likely prove the major test for Hibsago's launch, per the analysts' note Wednesday. The Jefferies team cautioned that the real-world treatment journey with GSK's new drug may be "less simple despite self admin."
The analysts also spotlighted Hibsago's black box warning for both hepatic flares and thrombocytopenia, noting that the subsequent every-other-week or weekly monitoring burden patients will face could in turn "work against the commercial uptake and could slow adoption outside specialist hepatology centers."
Nevertheless, the green light marks a major opportunity for GSK in the United States, where an estimated 1.7 million people are affected by chronic hepatitis B. However, the FDA nod is not Hibsago’s first.
Initial global clearance for the medicine came by way of Japan’s Ministry of Health, Labour and Welfare in late August, with a similar functional cure label in adults with CBD already experienced with nucleos(t)ide analogues and who meet certain viral markers.
GSK is seeking approval of Hibsago in multiple territories, including Europe and China, and said Tuesday that it expects more regulatory decisions on the medicine to land “in the coming months.”
“We are taking advantage of every regulatory pathway to accelerate the access of this medicine to patients,” Melanie Paff, Ph.D., GSK’s medical development leader for hep B, said on a media call about the bepirovirsen phase 3 data earlier this year.”
Editor's note: This story has been updated with additional detail from an analyst note.