vertex's latest press release

http://investors.vrtx.com/releasedetail.cfm?ReleaseID=522615

Telaprevir Phase 3 Program Complete; Rolling NDA Submission On Track

In the third quarter, Vertex completed its Phase 3 registration program for telaprevir. The company remains on track to complete the submission of its rolling New Drug Application (NDA) for telaprevir in combination with pegylated-interferon and ribavirin in the fourth quarter of 2010 with clinical data from its three Phase 3 trials in people who had not been previously treated for hepatitis C and in people who received prior treatment but were not cured.
Phase 3 ADVANCE and ILLUMINATE Trials to be Presented at AASLD This Week

Vertex expects that final sustained viral response (SVR or viral cure) and safety data from the Phase 3 ADVANCE and ILLUMINATE trials will be presented as part of oral presentation sessions at the upcoming annual meeting for the American Association for the Study of Liver Diseases (AASLD or The Liver Meeting), being held October 29 to November 2 in Boston. In total, eight Vertex abstracts were accepted for presentation at the AASLD meeting.
Initiation of Phase 3b Clinical Trial to Evaluate Twice-Daily (BID) Dosing of Telaprevir

Vertex today announced the initiation of a Phase 3b clinical trial to evaluate twice-daily dosing of telaprevir (1,125 mg; BID) compared to three-times-daily dosing of telaprevir (750 mg; q8h) in combination with pegylated-interferon and ribavirin for people with genotype 1 hepatitis C. Patient screening for enrollment in the study is expected to start in November 2010. Additional details on this trial were provided today in a separate press release.
Ongoing Phase 2 Trial Evaluating Combination Regimens of VX-222 and Telaprevir

Vertex announced today that it has modified its clinical trial evaluating telaprevir dosed in combination with Vertex's lead HCV polymerase inhibitor, VX-222. The company will discontinue Arm A of this study as a result of patients meeting a pre-defined stopping rule related to viral breakthrough during the first four weeks of dosing. Arm A was designed to evaluate a two-drug regimen of VX-222 (low dose; 100 mg) and telaprevir (1,125 mg) both dosed twice daily without pegylated-interferon and ribavirin. The additional three arms of the study are continuing without modification, and no viral breakthrough has been reported in these arms.
This Phase 2 proof-of-concept trial began dosing patients in August 2010 and is designed to evaluate safety and SVR rates using 12-week response-guided regimens of telaprevir/VX-222-based combination therapy in people with genotype 1 hepatitis C. The trial is continuing to evaluate treatment regimens that include four-drug regimens of telaprevir, VX-222, pegylated-interferon and ribavirin, as well as a two-drug regimen of only telaprevir (1,125 mg) and a higher dose of VX-222 (400 mg), both dosed twice daily.
Trial sites have now completed patient recruitment, which Vertex expects will enable it to reach the initial target enrollment of 100 patients for the study. Vertex expects to obtain on-treatment clinical data from this trial in the first half of 2011 and SVR data in the second half of 2011.

[Willy50]

No, this is a different trial using TVR and a polymerase inhibitor; VX-222.  It has little or nothing to do with the anticipated release of Telaprevir, other than it anticipates that TVR will be approved.  
In this case the actual trial consists of adding one more component (VX-222) to existing FDA approve drugs for treating HCV (assuming that TVR will be approved shortly), and it may also prove that drugs can be eliminated (IFN and RBV) and treatment time could be reduced to 12 weeks for responders.

Ultimately it may also prove an increased SVR rates for past TX failures, hope for people who cannot treat either with IFN or RBV, and due to a broader range of antiviral effectiveness it could also further improve the SVR rates for geno2's, g-3's and g-4's.  TVR has shown to not be especially effective in G-3's and 4's.

One might also assume that the dual PI's, with no or reduced use of IFN and RBV could be used to treat some patients at or near decompensation with decreased risk and greater effectiveness, thus possibly sidestepping the need for transplantation.

willy

[it'sallgood]

bummer, looks like we will using ribaviron and interferon for a while longer.

Vertex announced today that it has modified its clinical trial evaluating telaprevir dosed in combination with Vertex's lead HCV polymerase inhibitor, VX-222. The company will discontinue Arm A of this study as a result of patients meeting a pre-defined stopping rule related to viral breakthrough during the first four weeks of dosing. Arm A was designed to evaluate a two-drug regimen of VX-222 (low dose; 100 mg) and telaprevir (1,125 mg) both dosed twice daily without pegylated-interferon and ribavirin.

[HectorSF]

Thank you for the update. I know many are waiting to treat with Telaprevir next year.

Hectorsf

[Willy50]

Strictly speaking..... it is just Arm A that was discontinued.

Arm B is also a no riba arm, but features 4 x the VX-222 dose.  One might speculate that there will be a higher rate of success, but perhaps a less than stellar performance, but there are people who need to treat and whom cannot take extended or high doses of riba.  This form of treatment, while perhaps being considered a failure buy some could STILL be a Godsend for many of people who cannot take extended periods of IFN or RBV.  The cure rate won't be as good as others but it can still possibly cure some "niche" patients.  Success or failure is all a matter of perspective.  Vertex will know more when they compare it to the other no-riba Arm B.

Since both of the arms are backed us with 24 weeks of SOC we could still ultimately see SVR's and ultimate success, but it would appear that they know that this doing combination may not be the best route.  One also has to wonder whether RBV in the first 4 or 6 weeks may also be all that is needed.

When I first saw the size of the trial, I was surprised at how small the arms were; only 25 people per arm.  One can now better understand the rationale for that.  Vertex was able to through trial design abler to discriminate the performance of the 4 arms but where there could be break through and resultant viral resistance issues, they were able to limit the number of people who may face the resultant issues.  In this case 25 people in that arm, half of whom may respond and SVR via the 2 dose compound and perhaps 1/2 of those may ultimately succeed with the followup SOC treatment on the back end of the arm.

I'm sure we will know more later, but that's how I read this.

willy

[nygirl7]

A long time back now Susan got the no riba arm of a trial and it did not work. I am therefore not suprised to see such low numbers of the patients in the arms, it makes sense.

I too think interferon and riba will be with us much longer. wishing it were not true for someone like Mr. Beagle and his thalessemia so much though.

[Willy50]

Vertex reported that there were no viral breakthroughs in ANY of the other arms, one of which would include Arm B which was a no-riba arm.  I therefore believe it is too soon to write off the notion that one will need IFN and RBV to treat.  

Vertex Trial design has people who meet certain response criteria end TX after 12 weeks; not bad for a G-1treatment.

The down side of small arms is that if you have a few extra resistant folks in Arm A or some more responsive in Arm B it can really skew the results.  25 people per arm may be a bare minimum to infer results.  

Vertex reports that doing will end in the first half of 2011 and SVR rates in the 2nd half of 2011.  Since there is very little relapsing in the PI trials they will probably know the results long before the official 24 week PCRs occur, although perhaps they will see a higher percentage of these where people only treat for 12 weeks, and perhaps more still where people treat without RBV.

I know people with thalessemia who have successfully treated with IFN and RBV, but for "only" 24 weeks due to their geno-2 status.  These new forms of TX will cure a large number of us.  The key then, may be staying healthy until such a day may come.  

willy

[nygirl7]

It looks a long way away for anyone except geno1s - especially when you have want to take away the riba but I am certain that if the odds were so great that someone in his shoes could succeed he would try it.  He tried so HARD it was so dreadful that he should not succeed. He is always the one I think of us 'brave' for what he endured just trying to remain on SOC.

Everyone with liver damage of course she stay as healthy as possible until such a day comes!

[yoyoma123]

so this means that telaprevir will not be coming out in 2011?

[Willy50]

No, this is a different trial using TVR and a polymerase inhibitor; VX-222.  It has little or nothing to do with the anticipated release of Telaprevir, other than it anticipates that TVR will be approved.  
In this case the actual trial consists of adding one more component (VX-222) to existing FDA approve drugs for treating HCV (assuming that TVR will be approved shortly), and it may also prove that drugs can be eliminated (IFN and RBV) and treatment time could be reduced to 12 weeks for responders.

Ultimately it may also prove an increased SVR rates for past TX failures, hope for people who cannot treat either with IFN or RBV, and due to a broader range of antiviral effectiveness it could also further improve the SVR rates for geno2's, g-3's and g-4's.  TVR has shown to not be especially effective in G-3's and 4's.

One might also assume that the dual PI's, with no or reduced use of IFN and RBV could be used to treat some patients at or near decompensation with decreased risk and greater effectiveness, thus possibly sidestepping the need for transplantation.

willy

[spectda]

why would you say that. It states that the application for telaprevir will be submitted at the end of 2010 which means it should be available mid to late 2011.

[yoyoma123]

Perfect, thanks

[djbn13]

At my last appt with the hep doc at kaiser a few week ago he said they have been getting memos from administration to be prepared for the new drugs to be out around mid 2011 he said they have literally hundreds of people waiting for this and administration wants to be ready.

I guess we are all coming out of the warehouse next year

[willing]

the equivalent press from release from Merck is
http://www.merck.com/newsroom/news-release-archive/research-and-development/2010_1001.html

note "As previously reported, Merck plans to submit a New Drug Application (NDA) for boceprevir to the U.S. Food and Drug Administration (FDA) on a rolling basis, and expects to complete regulatory submissions in the U.S. and E.U. in 2010."

so maybe those rumors are accurate and there's some hope for boce by 6/11.