Telaprevir - 18 yes 0 no

[frijole]

Whew - that was dicey.  One of the FDA advisory committee panelists was agressive in his pursuit of issues with the rash, but in the long run, he and everyone else on the panel voted to approve.

Now it goes to the FDA.  Approval date (or not) is May 23. Some people are betting that the FDA will announce both BOC and TEL on May 7 - the date for Boceprevir approval (or not)

[Andiamo1]

I am surprised that they did have a trial with a lead in.  I do believe they think it has no value, but you could be right and it is business.  

I googled the trial and found many references to the lead in data.  This is one example:

"SVR rates for the telaprevir simultaneous start arm and the delayed start arm were 64% and 66%, respectively, overall, based on an intent-to-treat (ITT) analysis. For the primary analysis, the SVR rates for the telaprevir simultaneous start arm, delayed start arm and control arm, respectively, were 83%, 88% and 24% in relapsers (p<0.0001); 59%, 54% and 15% in partial responders, (p<0.0001); and 29%, 33% and 5% in null responders, (p<0.001)."

It looks like the results were withing the standard deviation of the trial.  So, I have no idea why the data was not submitted.

[willing]

Vertex definitely  has data on patients treated with  lead in and has submitted part of this to the FDA. See page 60 of the 147-page Vertex submission which spells out the study design for trial C216(aka Realize). The lead-in arm included 264 patients.

Unlike Merck, Vertex submitted no data on how response during that lead in affected outcome. The Merck data shows a very strong impact of poor lead-in response on outcome.  It would be  helpful to patients planning triple tx to see how this played out for tela, particularly across different prior tx groups. We can speculate about why this has not been released  -  my hunch is business interests  beat out patient interests.

The benefit of lead in is not a significant improvement in outcome - but critical information about what your personal SVR odds are with triple tx before the first PI pill.  Relapsers don't need to bother,  but anyone with a weak past response who is uncertain about whether it's worth trying  will benefit.

[coeric]

i am delighted that there are two DAAs about to be approved.

the following is from the Antiviral Drugs Advisory Committee April 28, 2011 Briefing Document.  perhaps the results of this study lead the investigators to conclude that the lead-in was not needed.  also you make a good point about not prolonging the tx longer than is necessary.  thank you.

C216 also evaluated the effect of a 4-week lead- in period with Peg-IFN/RBV before the telaprevir-treatment phase
Overall, a lead-in with telaprevir relative to Peg-IFN and RBV did not result in added clinical benefit relative to simultaneous start of telaprevir and Peg-IFN/RBV:
SVR24 rates were similar between the T12/PR48 and T12(lead-in)/PR48 groups for prior relapsers, prior partial responders, and prior null responders. The difference in SVR24 rates (T12/PR48 versus T12(lead-in)/PR48) with 95% CI was -4% (-6.4%, 10.4%) for prior relapsers, 5% (-26.2%, 12.64%) for prior partial responders, and -2% (-12.3%, 17.7%) for prior null responders.

[Andiamo1]

Vertex never had a trial with a lead in, so they have no data to present.  At least that is to the best of my knowledge.

Their scientists do not believe that a lead in is useful.  

Eric

[coeric]

thank you both for your opinions that the resistance is overblown. willing i am impressed with you ability to continue contributing considering your situation.  makes me thing i might be able to tx.

it is interesting that vertex has not released the lead in data.  but perhaps as was suggested earlier - vertex is interested in presenting tela as a 6 month tx for most and not a 7month tx.  
eric

[Andiamo1]

I have no justification for them not releasing data.  They think they are much more forthcoming than Merck.  I don't know if that feeling is justified or not.  They are a small company and could have been so focused on FDA questions that they just didn't pass all the data to their PR department.  I am just guessing at that.

I have spent some time with them and I am convinced that they believe they have presented all the data.  That does not mean they did though and I have no explanation if there is a discrepancy between what you believe and what they believe.  I would love to pursue it and I will if I ever get to meet their upper management again.

Vertex believes that the virus will revert to the wild type within 2 years of treating.