Vaccine for hepatitis B may allow patients to stop antiviral therapy
Most patients in VTP-300 trial eligible to stop such meds after 6 months
Most people with chronic hepatitis B enrolled in a Phase 2b clinical trial were eligible to discontinue their use of standard antiviral medication six months after starting a treatment regimen based on the experimental vaccine VTP-300.
That’s according to interim data from the clinical trial, called HBV003 (NCT05343481), that were announced by VTP-300’s developer Barinthus Biotherapeutics.
Based on the positive results, the company has said it will be focusing resources on developing VTP-300 for hepatitis B, as well as advancing its investigational vaccine VTP-1000 for celiac disease. Celiac disease is an autoimmune disorder marked by intolerance to gluten.
“Following the positive VTP-300 Phase 2 data in hepatitis B virus (HBV) in the second quarter, we made the strategic decision to prioritize our HBV and celiac disease programs,” Bill Enright, CEO of Barinthus, said in a company press release.
Enright added that these two programs “have the greatest probability for success and value creation, and represent significant opportunities in therapeutic areas with substantial unmet patient need.”
VTP-300 vaccine for hepatitis B combines 2 harmless viruses
HBV is the virus responsible for hepatitis B, a type of liver inflammation. While some people are able to clear HBV, in many patients the virus causes a chronic or long-lasting infection, which can set the stage for serious problems like cancer and liver failure.
Standard treatment for chronic hepatitis B involves nucleos(t)ide analogue therapy (NUC), which are antiviral medicines that help prevent the virus from replicating.
VTP-300 is an experimental vaccine designed to prompt the immune system to attack and destroy the hepatitis B virus. It combines two harmless viruses, called ChAdOx and MVA, that have been modified to carry information coding for different HBV molecules. Previous research suggested that these viruses are the most effective clinical platform to generate immune responses against the hepatitis C virus and other infectious agents.
Barinthus now is running the Phase 2b HBV003 study to test VTP-300 in combination with a low dose of nivolumab in people with chronic HBV infection who are on stable standard NUC. Nivolumab is a medication designed to activate the immune system, which is already approved to help treat certain forms of cancer.
All participants receive the ChAdOx part of the vaccine on day one, but distinct regimens of the MVA vaccine part and nivolumab are being tested in terms of their timing of administration and MVA re-dosing.
The study’s main goal is to assess the proportion of patients with a specific degree of reduction in the levels of HBsAg, a protein that the virus uses for infection, after six months of treatment. Those meeting certain response criteria are eligible to stop NUC treatment.
Over 75% of patients found eligible to discontinue antiviral medications
Interim findings, at a data cutoff date of April 15, concerned outcomes from 21 participants who were in the study for 169 days, or about six months. Before entering the trial, all had HBsAg levels no higher than 200 international units per milliliter (IU/mL).
Data showed that 16 patients (76%) were eligible to discontinue NUC at the time of assessment. Seven of them did discontinue antiviral therapy, of whom five (71%) had remained off NUCs at data cutoff. This included one patient who had been off antiviral medications for more than 10 months.
At six months or later, 67% of the 21 patients had HBsAg levels lower than 10 IU/mL, with four patients showing undetectable HBsAg at any time during the study. In two patients, HBsAg has been undetectable for at least four months.
Tests of patients’ immune cells suggest that VTP-300 is activating the immune system to go after all of the HBV proteins coded by the vaccine, as intended.
Towards the end of the year we look forward to sharing updated data from our HBV program as our two Phase 2 trials utilizing VTP-300, which are evaluating a potential functional cure regimen, mature further.
No serious side effects related to treatment have been reported in the study; the most common safety issue documented was abnormal thyroid function. One patient discontinued treatment due to adverse events, according to Barinthus, though the company did not provide further details.
A separate Phase 2a trial, dubbed IM-PROVE II (ACTRN12622000317796), is testing the combination of VTP-300 and NUC, with or without low-dose nivolumab, along with imdusiran, Arbutus BioPharma’s experimental immune-modulating treatment.
Participants in that study are given either VTP-300 or a placebo, and recent results indicated that patients given the active vaccine were more likely to meet criteria for NUC discontinuation.
Barinthus expects to announce updated interim results from both HBV003 and IM-PROVE II later this year.
“Towards the end of the year we look forward to sharing updated data from our HBV program as our two Phase 2 trials utilizing VTP-300, which are evaluating a potential functional cure regimen, mature further,” Enright said.
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