Vaccine Candidate Shows Sustained Reductions of HBsAg in Chronic Hepatitis B Patients
November 8, 2022 • 2:22 am CST
by Halcyon Marine
(Precision Vaccinations)
Vaccitech plc announced yesterday an update to the interim analysis of safety and efficacy data from its HBV002 phase 1/2 clinical trial that shows VTP-300 induced meaningful, sustained reductions of HBV surface antigen (HBsAg) in people with chronic hepatitis B (HBV).
HBsAg is a hallmark of chronic HBV infection.
A robust T cell response against all encoded antigens was observed following VTP-300 administration, notably for marked CD8+ T cell predominance.
Declines were most prominent in patients with lower baseline HBsAg.
Fewer than 10% of patients on current standard-of-care HBV therapies achieve sustained HBsAg decrease or loss, a state associated with a functional cure of the disease.
"The updated interim data from this Phase 1b/2a study continues to support the potential of VTP-300 as a critical component of a functional cure for people with chronic hepatitis B," said Thomas Evans, M.D., Chief Scientific Officer of Vaccitech, in a press release on November 7, 2022.
"The prominent effect we are observing in patients with lower starting HBsAg levels supports the ongoing collaborative study with Arbutus Biopharma's siRNA, AB-729, which has been shown to reduce HBsAg below 100 IU/mL in a majority of patients."
"In addition, we believe patients experiencing declines in HBsAg due to VTP-300 could benefit further from additional VTP-300 boosters, which we are evaluating in an additional ongoing study."
Patients in Groups 2 and 3 also demonstrated a robust CD8+ T cell response against all encoded antigens; core protein, polymerase, and surface antigens.
VTP-300 was administered as a monotherapy or in combination with a single administration of low-dose nivolumab at the time of the booster dose was administered with no treatment-related serious adverse events and infrequent transient transaminitis as of September 28, 2022.
In the VTP-300 monotherapy Group 2 (N=18), five patients had baseline HBsAg under 100 IU/mL. Three of those five patients showed meaningful and durable reductions of HBsAg of 0.9, 1.0, and 1.4 log10, respectively, five months after the last dose of VTP-300.
Furthermore, these reductions persisted in all three patients at eight months after the previous dose.
Group 3 (N=18) patients received VTP-300 in combination with a single low dose of nivolumab at the time of the booster dose. The mean log10 reduction in HBsAg was 0.8 (n=18) at three months, 0.9 (n=10) at six months, and 1.3 (n=7) at nine months, with more prominent declines observed in patients with baseline HBsAg lower than 1,000 IU/mL.
Five patients in this group had baseline HBsAg lower than 100 IU/mL, of which four had declined over 0.6 log10.
Moreover, two patients developed non-detectable HBsAg at three months, and one was evaluated at 6 and 9 months and continued to maintain non-detectable HBsAg.
The company confirmed enrollment in the HBV002 trial is complete, with a final update expected early in the second quarter of 2023.
And a trial to evaluate the timing of low-dose nivolumab and additional doses of the MVA boost component of VTP-300 (HBV003; NCT05343481) has been initiated in multiple countries within the Asia-Pacific region.
Other hepatitis vaccine news is posted at PrecisionVaccinations.com/Hepatitis.
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Staff Review