At EASL, SGP’s Boceprevir trial group presented an interim SPRINT-1 result and claimed that it had shown a "new treatment paradigm". The treatment protocol includes a 4 wk SOC treatment prior to the application of their PI. They thought that this is superior because their PI goes into action only after IFN stimulation of immunity grows to be most effective, and it can suppress mutant growth. The following is a straight quote from the abstract:
Conclusions. Four weeks of treatment with PEG/RBV prior to boceprevir administration markedly increased RVR and EVR and reduced viral breakthrough by 50%. This new treatment-paradigm has the potential to maximize efficacy of multi-drug combinations and minimize the risk of resistance by identifying responders to PEG/RBV. Interim results also demonstrate that full dose RBV is optimal. _____________________________________
The design of the new TVR trial led by Tibotec has the appearance of testing their hypothesis in a more logical way; One treatment arm placed the 4 week SOC treatment time before a 12 wk of TVR treatment and the other arm has the 4wk SOC after the 12 wk TVR treatment, so that the two arms receive an identical amount of IFN/RBV.
Treatment group A will receive telaprevir with standard treatment for 12 weeks; followed by placebo with standard treatment for 4 weeks; followed by standard treatment for 32 weeks. Treatment group B will receive placebo with standard treatment for 4 weeks; followed by telaprevir with standard treatment for 12 weeks; followed by standard treatment for 32 weeks. Treatment group C will receive placebo with standard treatment for 16 weeks; followed by standard treatment for 32 weeks. ___________________________
A short pretreatment with SOC may have a merit and enhance the efficacy of PIs. The new trial can address the efficacy vs risk for allocating a SOC treatment time before PI rather than placing all of SOC after PI.
While I don't think changing the Phase III protocol from Prove-3 changes the possibility of early approval, I think not proceeding with an equivalent Phase III building the success of Prove-3 seems nuts.
The whole idea here is to get an effective drug approved as fast as possible. The results in Prove-3 for treatment failure patients was very good. Why add new variables that may, or may not, contribute to positive results. Especially,if you can't predict the results.
Maybe now we really understand why Dr. Lewis-Hall was hired!!!
The FDA personnel in charge might be suspicious of PROVE 3 results because they are too good to believe. They may throw questions like "how well did you screen patients?", or "how are you sure there were no pretenders who are actually treatment naive patients?" Study 107, if the final results will be as good as the early results indicate, should answer these questions because Study 107 patients are documented by the trial physicians. The FDA may raise more questions such as "Study 107 patients were treated with TVR not long after the termination of SOC, and there might be a SOC sensitization effect." The new Phase III can also silence such doubters. You can not go too slow with the current FDA.
I think there are a variety of reasons for the design of the Phase III for treatment experienced. You've hit on one. I'd like to add another connected one. These trials are also run with an eye toward eventual marketing. Anyone in this business should know how Schering plays the game - down and dirty and ready to distort any numbers for corporate gain. If Schering happenned to get results in their treatment experienced trial - which has yet to start - that could be construed with any possible manipulation as better than Vertex, they would trumpet it to all who would listen. By running the trial as designed, Vertex should be able to put the lid on Schering's bs.
Also, as a patient, I would have the prove 3 24 week data along with three sets of 48 week data to help me make up my mind.