Well, simeprevir doesn't need to be boosted with ritonavir, as does ABT-450.
Ritonavir boosting is a clear indication that there's room for improvement.
Seeing 90+% SVR rates with the first generation oral combo from GILD brings into question the long-term utility of the P.I. class. The idea of developing a more potent, pan-genotypic P.I. is perhaps short-sighted because you are still working within a class with a history of safety issues and that doesn't co-formulate well with other drugs. The NS5A class is the second most desirable class for oral therapy due to it's benign safety profile alone or in combination. A best-in-class NS5A should safely fill in the efficacy gap (across genotypes) left by a highly-potent nucleotide backbone.
Put it this way. ABBV has a very competitive oral combo for GT1 therapy (including P.I.). Regardless no developer should be striving to replicate the ABBV model. It's flawed.
Medivir/JNJ will soon have an approved best-in-class P.I. The drug could see utility off-label as a second-line oral option. Maybe there will an oral licensing deal with a partner. I expect there will be a short window of opportunity within developed markets.
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