CARA CC notes: Actually, worth a listen for color on certain issues. Dropout rates were dose dependent (and some protocol violations/non-completions were not drug related), and they will not go forward with the 1.5mg/kg (highest) dose. Also, it is possible this dataset could be registrational. The curve really starts to separate at 6 weeks in the 8 week trial. Part B will be 12 weeks. The FDA might require that for the NDA, but they might not. This will not be known till the end of the year. Also, they note that nobody has required them to run protocols required for a scheduled drug (talking abuse here), and this is a good sign. They will ask for breakthrough designation, but of course, they're giving no odds. They do think the indication is sufficiently serious for that to be a possibility.
They will not attempt to go below .05/mg/kg because it is too hard to manufacture at that small a dose.
They also note that the FDA is looking for at least a trend in the secondary endpoint (Skindex, the QoL measure) for approval. They got more than a trend here, they got stat sig, so that's good. There is a tertiary endpoint, the Patient Global Impression of Change, which they did not show today, but this also showed good results. They expect to put put out that data soon.
The oral dose is not as bioavailable, so they may have to take a relatively high dose forward there. That could mean putting up with a slightly worse AE profile. Even so, they mention that they might be able to go the sNDA route for the oral formulation.
Back to the slide deck, I would note there don't seem to be any red flags in demographics. The only possible caveat being slightly higher starting baseline score in the .05mg/kg group for both primary and secondary endpoints. This didn't seem to bother anybody - no analyst asked about it. They said they would be drilling down more into that data.
One thing that struck me is the assertion that UP is more than a QoL issue, that it increases morbidity and even mortality. The former I can buy, while the latter seems a stretch to me, but I assume studies have been done on which to base this claim.
Regards, RockRat
