GSK has terminated a phase 1/2 hepatitis B trial after the therapeutic vaccine regimen failed to meet the efficacy endpoint, denting the company’s hopes of creating a functional cure for the infectious disease.
Investigators enrolled 135 adults with chronic hepatitis B to evaluate the effect of two viral vaccines and adjuvanted proteins. The study tested different dose levels and sequences—and included placebo—but the basic 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.
GSK tracked patients through to the evaluation of the primary efficacy endpoint 24 weeks after the last vaccination. The evaluation led GSK to terminate the trial, as the company explained in an update to the ClinicalTrials.gov listing late last week.
“Following the primary phase (24 weeks post last vaccination) the predefined efficacy endpoint was not met,” GSK said. “Noting the lack of efficacy and with the objective to prioritize patients’ safety GSK has decided on the early termination of the study.”
A spokesperson for GSK confirmed the termination via email, telling Fierce Biotech “that the study’s primary efficacy endpoint was not met [and] this vaccine candidate will therefore not progress to phase 3 studies.” No safety concerns were seen, the spokesperson said.
Another study of the adjuvanted vaccine regimen, which the company calls GSK3528869A, is still listed as active on the federal trial database. That study is 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.
GSK licensed the antisense oligonucleotide, which is also called GSK3228836, from Ionis Pharmaceuticals for $25 million upfront in 2019. Almost 30% of recipients had undetectable levels of hepatitis B surface antigen and DNA after receiving the treatment for 24 weeks, but the virus bounced back in most of the patients after treatment stopped. GSK is assessing whether GSK3528869A can help keep the virus suppressed.
The termination of the other trial is the latest in a series of blows to the hepatitis B pipeline. Roche axed phase 1 and 2 trials in a recent pipeline cull, 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.