Hibsago’s approval—a functional cure for certain patients with a hepatitis B infection—further validates Ionis Pharmaceuticals’ antisense platform, which has already generated two other new drug approvals this year.
The FDA has given the go-ahead to GSK and Ionis Pharmaceuticals’ antisense oligonucleotide bepirovirsen for the treatment of chronic hepatitis B virus infection, giving some patients the chance to potentially get off long-term medication.
Bepiroversen, to be marketed under the brand name Hibsago, can help patients achieve undetectable levels of the virus in the blood after six months—serving as a functional cure, according to GSK’s announcement on Tuesday.
GSK has forecasted peak worldwide sales of over £2 billion ($2.67 billion) for the drug, Reuters reported in May. BMO Capital Markets was more conservative in their estimate, projecting peak risk-unadjusted sales of $659 million in a Tuesday afternoon investor note.
Ionis will receive 10–12% tiered royalties on GSK’s sales—about $163 million, by BMO’s estimate—a “relatively modest” contribution to the company’s commercial business, the analysts wrote. But the approval “adds meaningful validation” of Ionis’ antisense oligonucleotide (ASO) platform after recent setbacks to the overall class, BMO continued. The firm pointed to the Phase 3 failure of Ionis’ AstraZeneca-partnered ASO Wainua in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) this summer and the September miss of Ultragenyx’s investigational ASO in Angelman syndrome.
Hibsago marks Ionis’ third ASO approval this year, following the September victory of Zanvastro for Alexander disease and the June clearance of Tryngolza to lower blood lipid levels and pancreatitis risk in patients with severe hypertriglyceridemia.
“While [Hibsago’s] approval was generally anticipated, we view this as another indication of the capabilities for the ASO platform Ionis has built,” BMO wrote.
Hibsago is given via subcutaneous injection every six months, and patients have the option to self-administer the drug after the first dose. It is indicated for use in combination with nucleos(t)ide analog reverse transcriptase inhibitors (NRTI) and is approved for adult patients who have no liver scarring, according to GSK.
Patients must have also been on NRTI treatment for at least six months and meet certain biomarker thresholds, as determined by an FDA-approved test.
Alongside Hibsago’s approval, the agency cleared Roche’s Elecsys HBsAg II quant II RxDx assay as a diagnostic device to identify patients with chronic hepatitis B who are eligible for treatment. The assay is also meant to help monitor patients while undergoing treatment.
Originally developed by Ionis, Hibsago was licensed by GSK in August 2019 with $25 million upfront plus up to $262 million in milestones. The antisense therapy targets the genetic material of the hepatitis B virus and tags it for destruction. This mechanism prevents the virus’ replication, while also boosting the immune system’s capabilities to fight off the infection. The FDA previously granted Hibsago breakthrough and priority review designations.
Hibsago’s approval was supported by data from the Phase 3 B-Well studies. The program consists of two late-stage studies, B-Well 1 and B-Well 2, which together enrolled more than 1,800 adults with chronic hepatitis B who had been exposed to NRTI treatment. Participants were given either Hibsago or placebo. Both trials primarily assessed for functional cure, defined as having no detectable levels of the virus for 24 weeks after ending all hepatitis B medication.
Detailed findings from the B-Well studies presented in May showed that Hibsago resulted in a 19% functional cure response rate. None of the patients on placebo hit functional cure.
In a key secondary analysis, GSK focused on patients with low baseline levels of the virus’ surface antigen. Hibsago treatment elicited a 26% functional cure rate in this subgroup, the pharma said on Tuesday.
“Hibsago provides a new treatment approach that gives some patients the possibility of maintaining control of the virus after all chronic HBV treatment has ended,” Wendy Carter, acting director of the FDA’s Office of Infectious Diseases under the Center for Drugs of Evaluation and Research, said in an agency release. “This approval represents an important advance for people living with this serious disease.”
As for safety, the FDA added a boxed warning on the Hibsago logo warning of serious liver reactions and low platelet counts, which the regulator said could aggravate the likelihood of potentially life-threatening bleeding. Other warnings for the drug include serious inflammatory side effects and declining kidney function.
