Replies to post #244422 on Biotech Values

[dewophile]

The 31% figure is impressive insofar as peg-IFN by itself has a 48w seroconversion rate of only 5-10%

To be clear the 31% is an end of treatment figure, not sustained rate off therapy. sustained rates of SAg loss w peg-IFN is generally felt to be 5% or less as far as I know, although it may be higher in certain special populations like perhaps lower baseline levels etc so I assume that is where you are getting the 5-10%?

Of course, a 48w regimen of VIR-2219 + peg-IFN won’t be any easier to tolerate than 48w of peg-IFN monotherapy, so this regimen is still far from the ultimate answer for treating chronic HBV.

They only tested 48 weeks because shorter regimens had very low rates of HBSAg loss (and none without peg-IFN).

[dewophile]

final data from the GSK phase 2b trial was published in conjunction w the abstract presentation. There isn't a whole lot to add to the top line data that were in the body of the abstract but a few selected excerpts:

https://www.nejm.org/doi/full/10.1056/NEJMoa2210027

In group 1, a total of 16% of the participants receiving NA therapy and 25% of those not receiving NA therapy with a low HBsAg level (≤3 log10 IU per milliliter) at baseline had a primary-outcome event, as compared with 6% and 7% of participants, respectively, with a high HBsAg level (>3 log10 IU per milliliter) at baseline

GSK said they are moving forward with a phase 3 monotherapy study in H1 2023. I have to think it will be focused on this subset with higher efficacy. I'm not sure how large a market they will capture but given the enormous size of the overall market they must think some patients will take 6 months of weekly shots for a 1 in 6 chance of a functional cure. If it were me I would probably hold out a bit hoping a more efficacious (likely combination) regimen became available, but it is not entirely crazy considering the remaining risk of HCC even with Nuke therapy. I have no idea if the FDA has already signed off on a phase 3 w fairly weak efficacy

Of the participants who had a primary-outcome event, 7 (50%) receiving NA therapy and 6 (50%) not receiving NA therapy had anti-HBs at the end of the trial

This is lower than I expected and I am not surprised GSK didn't mention this in their press release. The lower seroconversion rate vs say interferon might make these patients more at risk of reversion post week 24 than you see w interferon, but hopefully this is not the case

I think this got a NEJM publication because you have a novel treatment that can get you "cures" w shorter duration of therapy and better tolerability than interferon. I also think so far Bepi is more promising than any of the siRNA drugs (and other ASOs) to date, and the authors seem to agree

Clinical trials with siRNAs have shown HBsAg reduction to less than 100 IU per milliliter in up to 70% of participants, but no, or very few, participants had HBsAg loss

[dewophile]

VIR (GSK et.al. HBV)

VIR HBV—>48w VIR-2219 +peg-IFN—>31% HBs seroconverion:

Update from EASL

https://investors.vir.bio/news-releases/news-release-details/vir-biotechnology-presents-new-data-evaluating-potential-vir-1

Data presented in a late-breaker oral presentation from a Phase 2 clinical trial demonstrated that when VIR-2218, an investigational small interfering ribonucleic acid (siRNA), was given for 24 or 48 weeks on top of a course of up to 48 weeks of pegylated interferon alpha (PEG-IFN-?) (cohorts 4 and 5 combined), 16% (5/31) achieved sustained HBsAg loss 24 weeks following the end of treatment.

As you know I had expressed some skepticism regarding that 31% number