73% SVR for Prior Relapsers and 41% SVR for Prior Non-Responders per New Interim Telaprevir Data

[jmjm530]

This was posted previously but thought a different heading might cause more attention to the very encouraging Telaprevir results just released for both prior relapsers, prior non-responders.

Of note is that prior relapsers show a 73% SVR rate on 12 weeks of Telaprevir plus combo plus 12 weeks combo (24 weeks total treatment). And that 41% of previous non-responders also achieved SVR, a group that some were concerned would not be able to reach SVR because of previous non-response. These are intent-to-treat numbers so per protocol numbers would be higher.  Drop out rates were 7% in the Telaprevir group and 4% in the control group without Telaprevir. This seems less than in previous Telaprevir trials and I'm guessing it's because of the shorter exposure (12 weeks) to Telaprevir. Apparently more than 12 weeks of Telaprevir gives no additional benefit.

Interim Analysis Results

PROVE 3 is a randomized, double-blind, placebo-controlled Phase 2b study that enrolled patients who failed prior treatment with peg-IFN and RBV. Patients enrolled in PROVE 3 included prior non-responders (including null responders), prior relapsers and prior breakthroughs to peg-IFN and RBV treatment. The interim analysis included 453 patients that were enrolled and received at least one dose of study drug. In the interim analysis, 52% (60 of 115) of patients randomized to receive a 24-week telaprevir-based regimen (12 weeks of telaprevir in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone) achieved undetectable HCV RNA (<10 IU/mL; Roche TaqMan) 12 weeks post-treatment (SVR12). Of the 115 patients, 66 were categorized as non-responders to prior treatment (defined as patients who never achieved undetectable HCV RNA during prior treatment, including null responders), 40 were prior relapsers (defined as patients who had undetectable HCV RNA at the completion of prior treatment, but relapsed during follow-up), and 9 were prior breakthroughs (defined as patients who had viral rebound during prior treatment). Among patients receiving the 24-week telaprevir-based regimen, 41% (27 of 66) of the prior non-responders, 73% (29 of 40) of prior relapsers, and 44% (4 of 9) of prior breakthroughs achieved SVR 12.

“Patients who have not achieved a sustained virologic response with one or more courses of prior interferon-based therapy represent a significant unmet medical need. These patients have few or no available treatment options and they are at increased risk for progressive liver disease,” said John McHutchison, M.D., Principal Investigator for the PROVE 3 Study and Associate Director of Duke Clinical Research Institute.

A summary of available on-treatment and post-treatment antiviral data from the 24-week telaprevir-based regimen is presented below:
Undetectable HCV-RNA by Response to Prior Peg-IFN/RBV Treatment (PROVE 3 24-week regimen; 12 weeks telaprevir+peg-IFN+RBV, followed by 12 weeks peg-IFN+RBV);intent-to-treat analysis
                          Week 12    Week 24 (end of treatment)    SVR 12 (week 36; 12 weeks post-treatment)
Non-responders (n=66)   71%           65%                                     41%
Relapsers (n=40)      88%            83%                                         73%
Breakthroughs (n=9)   44%              44%                                        44%
Total (n=115)          75%          70%                                    52%

http://news.moneycentral.msn.com/ticker/article.aspx?Feed=BW&Date=20080609&ID=8746457&Symbol=VRTX

[jmjm530]

First sentence should have read in part  "...and not just those UND at EOT."

[jmjm530]

Susie: Does this mean that after 12 weeiks of telaprevir + 12 more weeks of SOC, 41% of previous non-responders will still be unetected?
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My take is that the 41% represents SVR  12 (UND at 12 weeks post tx)  for previous non-responders and not just those UND. Since the 12 week post tx UND seems to correlate very closely with the 24 week post tx UND, I would think that there's every reason to believe that these figures should hold up to a significant extent.

-- Jim

[willing]

Susie: my read is that it's much better than that. Of the 115 in the 12-triple+12-soc arm, 66 were non-responders using a "never achieved undetectable HCV RNA during prior treatment" definition. Of the 66, 27 were still UND 12 weeks after EOT. Some  reduction in the svr rate can be expected at the final 24 week test, but as I recall the number of relapses between 12 and 24 runs under 5%. Also, 66 is going to be too few to statistically distinguish "never got 1 log" vs "no 2 log by 12" vs "got 2 log but never got und" but hopefully they'll post the details at some point.

CA: I came across the following
http://www.ncbi.nlm.nih.gov/pubmed/18006035

which seems to provide a definite answer to your question about transmission of resistance strains. The A156T mutation confers resistance to all three NS3-targeted drugs (telaprevir, boceprevir, biln). If up to 1% of virions carry this mutation in a never-treated patient they are definitely fit enough to pass an infection. Given  the 1% it might take a transfusion rather than a needle stick.

[JennyPenny]

I only had a chance to glance at this cause I am due at my doctor's in 30 minutes. Does this mean that after 12 weeiks of telaprevir + 12 more weeks of SOC, 41% of previous non-responders will still be unetected? It will be interesting to see how many hold that SVR at 24 weeks EOT. I hope all of them do. Also, unless I am reading this uncorrectly, it does not say the previous non-responders never had a 2 log drop. I wish we could know that data as it is very important to some of us.

Susie

[willows]

Eric,

You thought we weren't paying attention to your test results.  I am, but I sure don't want to put any pressure on you about it all....it's all such a **** shoot.  Anyway, I apologize to you for my "overreacting"....it's good to be wrong some times!!

Here's crossing my fingers for more good news for you and about Telaprevir in the coming weeks.   It's hard to believe that the FDA would approve with just two trials and even harder to believe that by the end of this year we could have the drug available to us all.  Like a dream that I'm not sure I want to dream.....so I'll just keep waiting.

Willows

[Magnum]

Obviously great news... However, I have two friends now with advanced Cirrhosis who are living in constant fear. It's a shame they can't be given the drug without the possible placebo. I have elected not to travel 12 times from Las Vegas to L.A. for my treatment because of the 33% chance I will get a placebo.

Here in Las Vegas gas is today at $4.16 for regular unleaded and my Durango at 13 mpg would be a huge cost and loss if I were to get a placebo, to say nothing of the wear and tear on my body.

Rest assured that I will work tirelessly on Vertex to see if I can guarantee the Teleprevir instead of a placebo in exceptional cases such as myself (4 times non-responder), Susan (another marathon non-responder), and others who have also suffered a lot here through failed treatments. “The wheel that squeaks the loudest, gets the grease” Stay tuned...

Magnum