Doesn't sound so good. Mentions all the the patients that were warehoused are probably staying that way for better treatments.
VRUS earnings today mentions the Phase III beginning in 2012 that will include GT1. They also mention combo trials with their drug and BMY and combo trials with JNJ/Medivir.
Vertex has a really tough road ahead but at least this board will have it covered with it's conspiracy theories and other assorted nonsense.
"You missed my point. The fact that riba is required for 7977 means that there is likely an immune component of some sort in a 7977+riba combo. That being the case, assumptions of predicting G1 results from G2/G3 data become more tenuous."
The additive effects with Riba are quite incredible in the absence of interferon. We saw incredible results in mid-stage testing of PSI-7977/PegRiba in all genotypes and now we have seen a 100% SVR rate in GT2/GT3 patients after dropping the interferon. The 7-day PSI-7977 monotherapy study showed a greater drop in viral load with GT1 patients in comparison to GT2/GT3 patients.
I explained to gladpick that I am not predicting 100% SVR rates in GT1 patients. However your suggestion that the results remain tenuous seem to fly in the face of the data leading up to the event.
>> It is a trick, could turn out to be a treat, or a disastrous outcome. They do have guts!<<
they actually risk to obtain a restricted label from FDA, limiting the drug to INF intolerant patients, wonder how they will select these patients, how does one determine INF-intolerance in advance?
"interferon intolerant" are the patients, not the virus. This is a trick in combination with the FDA to allow for treatment on allegedly "interferon intolerant" subjects, so no one could invoke the ethical issue of the NEW STANDARD OF CARE Incivek, otherwise they will be force to do a trial against an Incivek/PegI/Ribavirin control group, and that is a big inclined step to take, they would have to at least prove "non-inferiority". Therefore, it is a bypass to easier recruitment of subjects without crying ethics problem. Vfin is correct that the virus should not be different (aka weaker)the weaker could turn out to be pharmaasset drug, that is why they are comboing with 10 arms in phase II in a massive fishing expedition, but it could turn out good for science and patients, they are taking big risks, but their comparison to Incivek regimes will be only "historical controls", more complex due to the inexistent "interferon intolerant" notion in any Incivek trial. It is a trick, could turn out to be a treat, or a disastrous outcome. They do have guts!
<<My post wasn't directed at Riba's role but the role of PSI-7977 in the absence of interferon. Riba is a fine partnering drug in which its method of action is somewhat a mystery. Even to the experts in the field.>>
You missed my point. The fact that riba is required for 7977 means that there is likely an immune component of some sort in a 7977+riba combo. That being the case, assumptions of predicting G1 results from G2/G3 data become more tenuous.
Vnfin, since you are the resident VRUS pumper on this board, can you please explain why the 280 patients in Pharmasset's Neutrino study will be required to be interferon intolerant? Why not go all the way and study any GT1 Hep C patient, regardless of their tolerance or intolerance of interferon or previous response to interferon? If they really can cure 100% of all GT1 Hep C patients with PSI-7977/ribavirin, they can then take 100% of the market share of these patients away from Vertex and Merck. They really ought to initiate such a study soon because there will be fewer of these patients left to treat as so many are being cured by the Incivek regimen.
My post wasn't directed at Riba's role but the role of PSI-7977 in the absence of interferon. Riba is a fine partnering
drug in which its method of action is somewhat a mystery. Even to the experts in the field.
<<PSI-7977/Riba is such potent, fast acting combo that an immune boosting agent like pegylated interferon may prove to be self defeating.>>
This logic flies in the face of current thought related to ribavirin’s role in the treatment of HCV.
From Brillanti et al., Digestive and Liver Disease 43, 425, 2011
Two major mechanisms of actionseemto play a role in the therapeutic efficacy of ribavirin against hepatitis C: (A) mutagenesis and error catastrophe and (B) up-regulation of genes involved in IFN signalling.
In 2000, Crotty and co-workers reported compelling evidence that ribavirin acts as a viral mutagen, causing a higher frequency of mutations and pushing viruses towards the threshold of error catastrophe . Differently from what happened with other possible molecular mechanisms of ribavirin against hepatitis C, this hypothesis was subsequently corroborated by more data [31–33]. Interestingly, although ribavirin has little effect on levels of HCV replication, mutagenic effects correlates with decreased infectivity in HCV cultures. It is not sure whether ribavirin concentrations obtained in vivo may parallel those needed to achieve mutagenic effects in vitro. In addition, the mutagenesis theory cannot be easily resolved by sequencingHCVgenomes from ribavirin-treated versus untreated patients, as the complexities of the interactions of the quasispecies with the host and the innate differences in the initial viral genomes infecting the host make it impossible to quantify changes in mutation frequencies caused by ribavirin mutagenesis accurately. This and the difficulties in defining the ideal timing of assessment of mutations for identifying increased mutagenesis may explain the lack of definite results noted in HCV-infected patients. In conclusion, the mutagenesis theory, even if not fully conclusive, is attractive to explain the limited decrease in viral loads, observed during ribavirin monotherapy, associated with a marked decline in liver disease activity. In a chronic HCV infection, ribavirin monotherapy may reduce the levels of infectious HCV produced in the patient, but it may not significantly affect the production of total HCV RNA. Therefore, may be that many of the HCV RNA genomes in ribavirin-treated patients are noninfectious.
In 2003, Brasier and co-workers discovered that ribavirin potentiates virus-induced IFN-stimulated response element signalling to enhance the expression of antiviral IFN-stimulated response genes (ISGs) in RSV-infected epithelial cells, suggesting a mechanism for the efficacy of combined treatment with ribavirin and IFN in other chronic viral diseases . Following this early experience, Feld et al. reported convincing evidence that ISG inducibility is important for the treatment response in patients with chronic hepatitis C, and that ribavirin may improve outcomes by enhancing hepatic gene responses to peg-IFN . Later, the same group provided more data supporting that ribavirin promotes IFN signalling, showing that ribavirin improves the viral kinetics of the early response to therapy in patients with an adequate initial response to peg- IFN. This response correlates with induction of IFN-stimulated cytokines . Data on the mutagenic effects of ribavirin and those on the promotion of IFN signalling are not unique and mutual exclusive. Collectively, these mechanisms may provide a molecular basis for the improved efficacy of combination therapy.
"PSI-7977/Riba is such potent, fast acting combo that an immune boosting agent like pegylated interferon may prove to be self defeating. "
Ok, I see where you are coming from. It remains to be seen though.
"Now by the above are you saying not including interferon would improve 7977 SVR to 100%"
No I didn't say that.
There's a possibility we could see higher SVR rates when interferon is removed. PSI-7977/Riba is such potent, fast acting combo that an immune boosting agent like pegylated interferon may prove to be self defeating.
"I'm quite sure every patient enrolled in this arm of the ELECTRON study has achieved a clinical cure."
How could that be when in the earlier study which included 7977+ribe+interferon and included easier to treat Geno 1 patients which also did not include any African decent patients, the SVR was I believe 93% and the tcontrol arm achieved i believe 62%.
Now by the above are you saying not including interferon would improve 7977 SVR to 100%?