Hopes for GSK3528869 appeared to be dashed in December when GSK terminated a phase 1/2 chronic hepatitis B study.\n GSK is prioritizing development of its hepatitis B treatment bepirovirsen as the pharma ends work on another potential functional cure for the infectious disease.On a media call Wednesday morning to discuss her company\'s fourth-quarter and full-year earnings, CEO Emma Walmsley said that when it came to the British pharma’s infectious disease pipeline, “we\'re prioritizing development of bepirovirsen, our potential functional cure for hepatitis B.”The pharma licensed the antisense oligonucleotide from Ionis Pharmaceuticals for $25 million upfront in 2019 and is currently aiming for an approval decision by regulators for chronic hepatitis B next year. The reemphasis on bepirovirsen came as GSK disclosed this morning that it has discontinued work on GSK3528869. The company had been holding out hopes that the candidate could be another functional cure for the infection—meaning it reduces hepatitis B virus DNA and viral proteins to undetectable levels. This stands in contrast to currently available oral antiviral therapies, which only suppress the virus.But those hopes for GSK3528869 appeared to be dashed in December when GSK terminated a phase 1/2 chronic hepatitis B study after the therapeutic vaccine regimen failed to meet the efficacy endpoint. The study tested different dose levels and sequences—and included placebo—but the idea was to prime the immune system with a viral vector encoding hepatitis B protein antigens, boost the immune system with a different vaccine and administer adjuvants to enhance the response.At the time, the pharma still had another study of GSK3528869 listed as active on the federal trial database. That study was evaluating the effect of giving vaccines to prime and boost the immune system—and adjuvants to enhance the response—after patients have received GSK’s bepirovirsen. But GSK confirmed in its earnings documents (PDF) today that it won’t be taking GSK3528869 forward.GSK isn’t the only pharma to have struggled with hepatitis B candidates in the clinic. Roche axed phase 1 and 2 trials in a recent pipeline cull, while Altimmune dropped a drug candidate after phase 2 data disappointed, and Ascletis Pharma stopped a hepatitis B program after the asset flopped in another indication.While bepirovirsen is taking priority, GSK still has a number of other assets in clinical development for chronic hepatitis B, including the hepatitis B virus-targeted siRNA GSK5637608, the PAPD5/PAPD7 inhibitor GSK3965193 and the TLR8 agonist GSK5251738. GSK also disclosed this morning that it had removed a capsid protein inhibitor for HIV called VH4004280 from its phase 2 pipeline. The company still has another HIV capsid protein inhibitor in multiple clinical trials in the form of VH3739937.The final drug to be pulled is the phase 1-stage GSK2556286, which is designed to inhibit the intracellular growth of Mycobacterium tuberculosis. The pharma has other tuberculosis candidates in the clinic in the form of the leucyl t-RNA synthetase inhibitor ganfeborole, the ethionamide booster alpibectir and the serine beta lactamase inhibitor sanfetrinem cilexetil. When it came to M&A, Walmsley told journalists on the media call that the company “continues to add new opportunities through targeted business development.” She pointed to the acquisition of Boston-based cancer-focused biotech IDRx last month as “a good example of what we want to do here.”
