Sofosbuvir and Ledipasvir Phase 2, and When Small Studies Make a Big Impact

NEJM Journal Watch

HIV and ID Observations

An ongoing dialogue on HIV/AIDS, infectious diseases, all matters medical, and some not so medical.

November 5th, 2013

Imagine for a moment the ideal medical future … there’s a vaccine that prevents the common cold … colon cancer screening no longer requires that horrendous “prep” … electronic medical records are easily accessible, intuitive, secure, and all communicate effortlessly with one another … your doctor’s office has an actual person who answers the phone instead of a pre-recorded list of “menu options” … and hepatitis C is cured with one pill a day taken for 8 weeks.

Not sure about the timeline for the first four, but based on this study of sofosbuvir and ledipasvir just published in the Lancet, the hepatitis C outcome is right around the corner:

In cohort A, SVR12 [no detectable virus 12 weeks after stopping treatment] was achieved by 19 (95%) of 20 patients (95% CI 75–100) in group 1, by 21 (100%) of 21 patients (84–100) in group 2, and by 18 (95%) of 19 patients (74–100) in group 3. In cohort B, SVR12 was achieved by 18 (95%) of 19 patients (74–100) in group 4 and by all 21 (100%) of 21 patients (84–100) in group 5 … These findings suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV, irrespective of treatment history or the presence of compensated cirrhosis.

You’ll note that the “groups” were pretty small, and that only one of them — group 1 — actually got just the one-pill sofosbuvir/ledipasvir combination for 8 weeks, but regardless, these are pretty spectacular results. Even the most “complex” treatment group in this study received sofosbuvir/ledipasvir plus ribavirin for only 12 weeks, which is light years from the complexity of our current interferon-based therapies. Light years better, of course.

And since sofosbuvir has already been reviewed by the FDA advisory panel, we should be getting at least this drug by December 2013 at the latest; the combination pill with ledipasvir could be available some time next next year (according to this article in the New York Times), and several other investigational HCV drugs will likely be approved soon as well (simeprevir this year too).

But calm down already. Take a deep breath. It’s a small Phase 2 study. Shouldn’t we be more cautious? Shouldn’t we avoid wildly overstating the importance of this particular treatment approach? Of course, that’s the prudent thing to do.

But can people with HCV and their treaters be ecstatic about these results anyway? You betcha.

Source

Also See: Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial