VIR-3434 Phase 1-study made by Vir Biotechnology

VIR-3434 is the name of a monoclonal antibody therapy (mca). It has been offered to me 2 days ago. I have time to answer till june, 21, 2022. It has been tested already successfully
with 40 healthy volunteers and 40 hbv-patients with suppressed viral load. The HBs Antigen has been reduced significantly.

Because i want to minimise risks i would like to know which serious adverse events are possible when i get mca in my body. The study had no grade 3 or 4 adverse events yet. What are your opinions?

My viral load from 20.may.2022 was 2320 IU/ml. I am HBe-Antigen negative. My blood group is A+. I did not take Tenofovir yet. They took some blood samples in the university hospital 2 days ago. The test from may was at the medical office of my brother in law.
I am still not vaccinated with mRNA-Vaccine. I take supplements.

The combined therapy VIR-2218 + VIR-3434 is in phase 2. Development Pipeline | Vir Biotechnology

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is this NAPs ?? @availlant
which country you are taking part

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It is in Essen/Germany. Nucleid Acid Polymer (NAP) is used by Replicor.

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Dear Koreaner81,

Correct regarding VIR-3434 and NAPs (REP 2139-Mg).

It is important to be careful and set expectations when assessing HBsAg response to therapy. While the HBsAg reductions achieved with VIR-3434 are “statistically significant”, they are not clinically significant in terms of potential to achieve functional cure.

Large clinical studies with pegIFN and phase II studies with NAPs demonstrate that a >4 log reduction in HBsAg from baseline during therapy is required to achieve functional cure of HBV infection.

This was verified last November with a large phase IIB study with combination therapy including an RNAi (JNJ-3938) where no patient achieved functional cure with 2-3 log declines in HBsAg. In fact, HBV rebound was observed following removal of therapy in this trial.

There will be no significant safety issues with enrolling in the VIR-3434 trial, but I would advise that you start NUC therapy (preferably TDF or TAF) regardless of your participation.

Early initiation of NUC therapy has been shown to be much better in preventing the development of liver cancer.

Best regards,

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The results in the mouse-models are encouraging if the dose will be increased in human studys. " Poster Presentations – VIR-3434
Preliminary blinded safety and tolerability results and HBsAg data from a Phase 1 trial evaluating VIR-3434 in 24 virally suppressed adults with chronic HBV infection who were randomized to receive a single dose of either 6 mg, 18 mg, 75 mg or placebo demonstrated:

  • A single dose of 6 to 75 mg of VIR-3434 resulted in rapid HBsAg reductions of >1 log10 IU/mL in most participants within approximately 1 week post-dose.
  • The largest (>2 log10 IU/mL) and most sustained reductions in HBsAg were observed in the 75 mg cohort.
  • Single doses of VIR-3434 were generally well tolerated; all AEs were grade 1-2. No clinically significant laboratory abnormalities or changes in liver safety parameters were observed.

Poster Presentation: Kosh Agarwal, M.D., consultant hepatologist and transplant physician at the Institute of Liver Studies, King’s College Hospital (Abstract #28863; Publication #839)

A preclinical analysis of VIR-3434 and the parent molecule of VIR-3434 (HBC34) in in vivo mouse models demonstrated:

  • VIR-3434 neutralized both HBV and hepatitis D virus infection with >5,000-fold higher potency than hepatitis B immunoglobulins in vitro.
  • In an HBV mouse model, the parent molecule of VIR-3434 blocked the spread of HBV infection and reduced HBsAg levels in chronically infected animals.
  • VIR-3434 in complex with HBsAg activated dendritic cells efficiently and induced CD4+ reporter T cell responses – the first steps towards eliciting T cell immunity and potential long-term control via a vaccinal effect."

Dear Koreaner,

Unfortunately, there is a limit to the amount of this antibody that can be used. The complex between HBsAg and the antibody is actually quite large becuase it is a complex of the the antibody and either a subviral particle or a viral (Dane) particle.

These “immune complexes” become trapped in the kidney filtration apparatus and if too numerous cause kidney inflammation (nephritis). See Nephritic Syndrome - StatPearls - NCBI Bookshelf for more information.

Thus the use of VIR-3434 (or any other similar antibody approach) will have to contend with this limitation. There is also the problem that there will almost certainly be strains of HBsAg which will not be recognized by VIR-3434 or any other HBsAg specific antibody. These “immune” escape strains of HBsAg are well documented in the literature.

Its also important to set expectations for clinical activity based on results in mouse models of HBV infection. Mouse models are very poorly predictive of the antiviral effects of new investigative therapies (for instance NAPs have no activity in mouse models and yet are the only agent that achieves HBsAg loss in humans). There are many technical reasons for this. I advise you to use clinical efficacy data as the only real and reliable barometer for the antiviral potential of new investigative therapies.

Best regards,