That's a question for the entire oral program, IMO. Given the much lower bioavailability of the oral formulation, are they going to be able to get sufficient receptor occupancy to keep the benign AE profile? I noted that while dizziness and headache did not seem to show dose response in this trial, paraesthesia and somnolence did (again, as you point out, small n). Does this imply that the former are on target effects, but the latter are not? I haven't studied the data on the target enough to say. If that were true, might we expect a more exaggerated version of this AE profile in the oral trials? I.E. same level of dizziness and headache, but more paraesthesia and somnolence? I forgot to mention the the CMO said patient perception of dizziness can in part be secondary to paraesthesia. In other words, he seemed to suggest that it's natural to feel a bit a dizziness when your face tingles. Muddies the issue a bit.
Cheers, Tuck |
