Japan Approves GSK’s Hibsago for Chronic Hepatitis B and Takeda’s Orzeyful for Narcolepsy Type 1

Japan Approves Hibsago for Chronic Hepatitis B

Japan has cleared GSK’s Hibsago, also known as bepirovirsen, for adults with chronic hepatitis B who have already received at least six months of nucleos(t)ide analogue treatment and meet specified viral-marker criteria. The decision marks the therapy’s first approval anywhere in the world and introduces Japan’s first treatment authorised to pursue a functional cure for chronic hepatitis B.

The Ministry of Health, Labour and Welfare granted the approval under Japan’s SENKU framework, which is intended to speed access to promising therapies for serious conditions with substantial unmet need.

Chronic hepatitis B remains a major health burden in Japan, where close to one million people are estimated to be living with the infection. The disease can progress to serious liver complications, including hepatocellular carcinoma, and is linked to approximately 4,000 deaths each year.

Hibsago is an antisense oligonucleotide treatment designed to reduce production of hepatitis B viral RNA and proteins. Its aim is to lower hepatitis B surface antigen levels, known as HBsAg, potentially enabling a patient’s immune system to maintain control of the virus after therapy has ended.

The Japanese decision was based on the Phase 3 B-Well programme. In the pooled study population, which included patients with HBsAg levels at or below 3,000 IU/mL, 19% of people receiving a six-month course of bepirovirsen achieved a functional cure response. No participants in the placebo group met that endpoint.

For the trial, a functional cure required hepatitis B viral DNA and HBsAg to remain undetectable for at least 24 weeks after all treatment was stopped. This outcome is clinically important because HBsAg loss has been associated with substantially lower risks of liver cancer and death.

Results were stronger in a subgroup with baseline HBsAg levels at or below 1,000 IU/mL. In that population, 26% of patients treated with bepirovirsen achieved functional cure, compared with none of the placebo recipients. Exploratory findings also showed that 49% of treated patients in the broader study group reached HBsAg levels of 100 IU/mL or lower by week 72, increasing to 62% in the lower-HBsAg subgroup.

GSK obtained rights to bepirovirsen from Ionis and worked with the company during development. Regulatory reviews are continuing in other markets, including the United States, while the company also investigates how the drug could fit into future sequential treatment approaches for chronic hepatitis B.

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Takeda’s Orzeyful Receives Japanese Approval for Narcolepsy Type 1

Japan has also authorised Takeda’s Orzeyful, or oveporexton, for adults with narcolepsy type 1, including narcolepsy with cataplexy. The oral medicine is the first approved therapy in Japan designed to address the orexin deficiency behind the condition rather than targeting individual symptoms separately.

Takeda discovered the medicine in Japan and is preparing for a commercial launch. The company said it intends to make the treatment available as soon as possible.

Narcolepsy type 1 is an uncommon, lifelong neurological disorder caused by loss of orexin signalling, which plays a central role in maintaining wakefulness. Patients may experience overwhelming daytime sleepiness, cataplexy, fragmented night-time sleep, sleep paralysis, hallucinations and cognitive difficulties.

The condition can affect work, education, relationships and day-to-day independence. Diagnosis is often delayed because the symptoms are varied and awareness remains limited, with patients reportedly waiting more than a decade on average before receiving a diagnosis.

Orzeyful is a selective oral agonist of orexin receptor 2. By activating that receptor, oveporexton is intended to replace missing orexin-related signalling, improve wakefulness and reduce REM-sleep-related symptoms such as cataplexy.

Japan’s approval was supported by Takeda’s global Phase 3 FirstLight and RadiantLight trials. Across the studies, oveporexton produced significant improvements compared with placebo across several measures of narcolepsy type 1, including wakefulness, daytime sleepiness, cataplexy frequency, overall symptom severity and quality of life.

At 12 weeks, participants receiving oveporexton showed better performance on the Maintenance of Wakefulness Test and lower Epworth Sleepiness Scale scores than those receiving placebo. In the group receiving the 2 mg twice-daily regimen, most patients achieved wakefulness measurements within the normal range on the Maintenance of Wakefulness Test. Nearly 85% also reached Epworth scores considered comparable with those of healthy people.

The treatment also substantially reduced cataplexy. Median weekly cataplexy frequency fell by more than 80% across dose groups over 12 weeks, while the median number of cataplexy-free days rose from none at baseline to roughly four to five days per week by the end of the study period.

On the narcolepsy severity scale, more than 70% of participants across dose levels reported mild disease severity after treatment. Nearly all patients treated with oveporexton, around 97%, also reported an overall improvement in their condition using the Patient Global Impression of Change assessment.

Quality-of-life scores improved as well. Trial participants reached results within the normative range on the 36-item Short Form health survey, with additional gains reported on the EuroQol five-dimension, five-level measure.

The approval gives Japanese adults with narcolepsy type 1 access to a new disease-focused approach that may shift treatment away from managing separate symptoms toward restoring the biological pathway disrupted by orexin deficiency.

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