Bepirovirsen Sodium

GSK's chronic hepatitis B (CHB) therapy notched its first-ever approval on Monday, nabbing a nod in Japan as its applications in the US, EU and China progress. Japan regulators greenlit Hibsago (bepirovirsen) as a functional cure for adults with a hepatitis B surface antigen (HBsAg) level of ≤3000 IU/mL who have received at least six months of prior nucleos(t)ide analogue (NA) therapy.The antisense oligonucleotide's clearance comes less than three months after GSK presented what it called "unprecedented" results from the Phase III B-Well 1 and B-Well 2 trials at the European Association for the Study of the Liver (EASL) congress.Pooled data from the two studies showed that patients with CHB who received once-weekly injections of Hibsago over the course of six months achieved a 19% functional cure response rate in the overall study population, a statistically significant result given the 0% cure rate for the placebo group, meeting the primary endpoint.Furthermore, in patients with low viral activity — defined as an HBsAg level of ≤1000 IU/mL, making up about 45% of all global CHB cases  — the Hibsago group saw a functional cure rate of 26%. Current NA therapies like entecavir and tenofovir require daily dosing, with patients at risk of relapse if treatment is stopped. They're also associated with a functional cure rate of less than 1% (see – Spotlight On: GSK delivers historic win for hepatitis B patients).After the B-Well readouts, FirstWord spoke with Calvin Pan, a professor of medicine in the Division of Gastroenterology and Hepatology at New York University Grossman School of Medicine, who called the data "a very important milestone" for CHB. "There are no competitors with comparable functional cure rates right now," he said, but noted that GSK will likely have to run strong peer-to-peer campaigns in the US to raise patient and physician awareness of Hibsago (see – KOL Views Q&A: GSK's bepirovirsen is one small step for HBV patients, one giant leap for HBV therapy).A decision from the FDA on Hibsago is expected in "the coming months," GSK said Monday. The UK pharma in-licensed the drug from Ionis Pharmaceuticals in 2019, and recently inked a distribution deal with Sino Biopharmaceutical to help its commercialisation efforts in China.

乙肝治疗正从“终身压制”转向“追求治愈”。 最近，GSK的乙肝新药在日本率先获批。这是全球头一回用反义寡核苷酸（ASO）技术治乙肝。 老药只能压病毒，新药想停药。 以前的核苷类药物能控制病毒复制，但清不掉肝里的病毒模板。患者一旦停药就容易反弹，往往得吃一辈子。 干扰素虽然能帮部分人转阴，但副作用大、疗程长。 这次的新药Bepirovirsen换了打法：直接破坏病毒的遗传成分。它还能大幅降低表面抗原，帮免疫系统重新认出病毒。 临床数据挺亮眼，但不是百分百灵。 做完半年治疗后，约19%的患者达到了功能性治愈标准。要是患者初始指标较低，成功率能到26%。 不过要注意，“功能性治愈”不等于把病毒彻底杀光。它是让身体在停药后自己能控制住病毒，从而大幅降低肝癌风险。 国内也在拼命追，最快2027年能用上。 这药目前在中国已经进了优先审评通道。预计最快2027年前后在国内上市。 除了它，国内还有浩博医药、恒瑞等多家药企在研发同类新药。有的国产管线早期数据甚至更好，比如浩博的一款药在小范围试验里治愈率到了70%。 离彻底消灭乙肝可能还有段路，但至少看到了停药的希望。