I would appreciate a little help in understanding IL28B. To my understanding when IL28B is identified it represents a sub type of Genotype 1 patients that are more responsive to treatment. What I'm confused with is the different IL28B types, such as cc, and tt, and if there are others. Is the cc type the only one that represents being more responsive, or is it all IL28B types? I only have a weak grasp of this and would greatly appreciate if somebody could enlighten me. I'm just trying to understand the relationship of SVR results between Vertex and VRUS drugs. I saw info on Vertex reducing treatment time to 12 or 24 weeks, and increasing SVR into the 90% range when using IL28B as a predictor. I also see VRUS using IL28B in selecting subjects for their posted results that include interferon, also with SVR in the 90% range. I just dont understand the difference between IL28B cc, and IL28B tt. Thanks in advance for anybody willing to enlighten me on this.
These patients have no other options so you can expect to see studies in this subgroup. Some patients don't respond well to interferon-based therapy so a highly potent oral drug like PSI-7977 is welcome news.
Interferon failures were already succesfully proven to respond to a treatment adding Incivek, or Victrelis, those were basic strictly required for approval of those two drugs. VRUS should take the double failures and proves their drug (failed interferons and then failed adding Victrelis, or Incivek).
"In one of their recent conference presentations, Pharmasset was asked to define interferon intolerant and was unable to come up with a consistent answer when asked 3 separate times by different analysts. "
VRUS wants to purposely leave it vague so that they later can massage and expand the group that the remimen is appropriate for. They dont want to be pinned down -- that is too limiting for their devious plans.
Just like SGP and their massaging of the data for Victrelis, only to find out later they could not fool the medical community!
Just to correct my statement. Interferon failures more likely than not won't be included in this group. I will ask IR. Regardless interferon failures should be more difficult to treat than "all patients with HCV" so focusing on this group of patients shouldn't raise any flags for the FDA.
"Fission is open label, but why not run it as I proposed in my last post?"
In FISSION note that the control group consisting of 24 weeks of Peg/Riba in GT2/GT3 patients is the existing SOC and PSI-7977/Riba is the proposed SOC. The open label study is designed to compare the two directly.
"Assuming Electron and Quantum data is good for GT1, why wouldn't Neutrino look only at GT1?"
Very good questions fade. NEUTRINO is designed to be agnostic to genotype (pangenotypic)
yet will be overweight in GT1 patients. Are we sure that once results from ELECTRON and QUANTUM are released the FDA won't require another study specific to GT1?
"Also, why look at interferon intolerant patients only in GT1? Why not just go as broad as possible in Neutrino and have the criteria simply be "patients with HCV"?"
Today interferon intolerant patients are the greater unmet medical need much like GT2/GT3 patients that require 24-weeks of PEG/Riba. This aspect of the design is clearly a result of consultation with the FDA.
Lastly, what is defined as interferon intolerant in the studies - any idea? Is this someone who was previously treated with old SOC and dropped out early?
Interferon intolerant patients can include contraindicated, substance abusers, interferon failures, or those that dropped at of interferon based therapy due to the awful side effects associated with treatment.
In one of their recent conference presentations, Pharmasset was asked to define interferon intolerant and was unable to come up with a consistent answer when asked 3 separate times by different analysts.
Ah, yes. Not thinking on all cylinders tonight :) I think I'm getting my physics terms confused.
I looked at the PR again. It was Fission I was confusing myself with. Fission is open label, but why not run it as I proposed in my last post? That would allow it to be blinded.
Positron is blinded, and I assume Neutrino will be blinded in the same way.
Couple more questions.
Assuming Electron and Quantum data is good for GT1, why wouldn't Neutrino look only at GT1? The reason I ask is because if Positron is specific to GT2/3 who are interferon intolerant, then why would VRUS need a second phase 3 trial aimed at the same patient population (GT2/3 who are interferon intolerant) but with the addition of GT1 who are interferon intolerant (and other rarer genotypes)? What advantage is there in having GT2/3 at all in Neutrino?
Also, why look at interferon intolerant patients only in GT1? Why not just go as broad as possible in Neutrino and have the criteria simply be "patients with HCV"?
Lastly, what is defined as interferon intolerant in the studies - any idea? Is this someone who was previously treated with old SOC and dropped out early? Is this someone who has never had interferon but just doesn't want to take it ever? Just seems a bit nebulous to me.
It's important to understand what third, gladpick, or VRTX for that matter care about isn't what the FDA cares about. What the FDA cares about is public health and meeting unmet need. GT1 data will be coming out from ELECTRON study showing the efficacy of PSI-7977/Riba just as it did in GT2/GT3. NEUTRINO is studying how the drug works in patients that can't take a P.I. when combined with interferon.