周末医疗脉搏：GSK的Bepirovirsen会成为下一个“乙肝巨头”吗

Justin Smith+44 20 7762 5899justin.smith@bernsteinsg.comRebecca Liang, Ph.D.+852 2123 2656rebecca.liang@bernsteinsg.comMiki Sogi, Ph.D.+81 3 6777 6991miki.sogi@bernsteinsg.comCourtney Breen+1 917 344 8407courtney.breen@bernsteinsg.comEve Burstein+1 917 344 8313eve.burstein@bernsteinsg.comLee Hambright+1 917 344 8429lee.hambright@bernsteinsg.comSusannah Ludwig+41 582 723 127susannah.ludwig@bernsteinsg.comWilliam Pickering, MD+1 917 344 8340william.pickering@bernsteinsg.comLance Wilkes+1 917 344 8501lance.wilkes@bernsteinsg.comDelphine Le Louet+33 1 42 13 92 93delphine.le-louet@bernsteinsg.com Specialist SalesChristian Moore+1 917 344 8555christian.moore@bernsteinsg.com (HCV). HCV is a blood-borne (i.e. transmitted blood-to-blood) virusthat targets the liver. If untreated, HCV can lead to cirrhosis (liverfailure) or hepatocellular carcinoma (HCC; i.e. liver cancer). HEPATITIS B: WILL THE UNMET NEED NOW FINALLYBE ADDRESSED? In January 2026, GSK published positive headline results for thephase 3 B-Well 1 & 2 clinical trials for bepirovirsen, a potential first-in-class treatment for chronic hepatitis B (CHB) due to launch in2H27/1H28.At this year’s European Study of the Liver (EASL)(27-30thMay) GSK will present the full data from these trials.Although CHB is the leading cause of liver cancer there has been nodrug innovation since 2005. EXHIBIT 1:Harvoni (GILD (O: Breen)) had an “Icarus-like” riseand fall At present, consensus (Bloomberg) estimates peak sales of ~ £900mfor bepirovirsen. But with company guidance (from the 2021 CMD)indicating peak sales potential of >£2Bn, we thought this was theperfect opportunity to remind you of what we know about chronichepatitis B (CHB), what the trial data for this drug has demonstratedthus far, and set out our case for why we think bepirovirsen salescould surprise on the upside. We also wanted to use this Pulse to outline our thinking for whywe think the commercial development of HBV medications willnot repeat the same “Icarus-like” fate that Gilead and AbbVie’shepatitis C (HCV) drugs (Harvoni and Mavyret respectively) had in themid-2010s. The hepatitis family and Gilead’s “Icarus” Curve There are five viruses making up the Hepadnaviride family (A, B, C,D, and E), of which the most famous member is likely hepatitis C Source: Wiki Commons HCV is well known because of its broadly researched interactionwith patients who have an alcohol use disorder (AUD - “alcoholics”).Heavy alcohol use has been shown to roughly double the risk ofprogressing to liver failure/cancer in HCV patients. In our view, HCVis also renowned because the “Icarus” type revenue curve Gileadendured with its launched various HCV medications across themid-10s. reduce the patient population). Hepatitis B (HBV): An Overview of a Disease with HighUnmet Need Hepatitis B (HBV) is (similarly to HCV) a virus that causes a liverinfection. The main difference (other than it being a different virus)is that HBV can be transmitted through body fluids, whereas HCV isstrictly a blood-borne virus. There is no HCV vaccine, but Gilead (O; Breen) developed various“viral cures” to HCV, meaning that once patients were treated,they exited the patient pool permanently. Harvoni, a direct actingantiviral (DAA), was launched at the end of 2014 and, in the first fullyear of launch (2015) delivered $14Bn in sales (Exhibit 2). When HBV infects the liver, it can cause jaundice (a yellow-ishpigmentation of the skin), fever, fatigue, nausea, and abdominalpain. Whilst most cases are acute (lasting < 6 months) and mostadults clear the virus with no treatment, chronic HBV (CHB) canlead to liver cirrhosis (liver failure) and hepatocellular carcinoma(HCC; i.e. liver cancer). In fact, CHB is the leading cause of both,thus all patients with HBV need to be regularly monitored. HBV was identified as a new DNA virus in the 1960s. But tracesof HBV have been found in ancient human remains going back atleast 10 millennia. Furthermore, there are references to this viruson Babylonian clay tablets, and Hippocrates described an epidemicof jaundice (a clinical sign of HBV infection) in the 5thcentury BC. Baruch Blumberg discovered the “Australia antigen” in 1963, whichlater became known as the hepatitis B surface antigen. These are“markers” on the outside of liver cells (hepatocytes) which allowthe body to recognize the virus, and induce the body’s immuneresponse and are now called HBsAg (Exhibit 3). A vaccine for HBVwas developed and launched in the US in 1986 by Merck & Co. (MP;Breen). The Recombivax-HB vaccine was the first vaccine to bedeveloped through genetic engineering. Quickly however, Gilead’s HCV portfolio’s revenues collapsedbecause(i)it was curing patients at a rate much faster thanpeople were being infected and(ii)the patient population wasnot mobilized (i.e. only patients with the most severe need wantedthe drugs), and(iii)increased competition from other players (e.g.AbbVie (MP; Breen) with Mavyret). All in all, this led to