Study 306B is the new clinical trial, which like Study 301, demonstrated a statistically significant reduction in dizziness. Oliveto believes having positive Northera data from Study 306B that is consistent with Study 301 works in Chelsea's favor. Two positive studies are always better than one. Oliveto is right.
But... Study 306B isn't pristine, so Chelsea will need to explain some of the trial's quirks and inconsistencies. For starters, Study 306B is really a "do over" trial stemming from the failure of Study 306. Study 306B has also undergone at least two major revisions to its statistical analysis plan, including changing the primary endpoint from fall reduction to reduction in dizziness score.
But despite these changes, the conduct of Study 306B was not adversely affected and reduction in dizziness is the signal measure of clinical benefit for the treatment of NOH deemed most important by the agency, Oliveto says.
Fine, makes sense, but let's not be entirely confident until we see what FDA says in the Northera briefing documents.
Another Study 306B issue: The primary endpoint was achieved based on a modified intent-to-treat patient population. Chelsea excluded patients who dropped out of the study during the titration phase. (More patients randomized to Northera dropped out than those on placebo.)
What happens to Study 306B if the most conservative statistical analysis is applied?
"The study loses statistical significance," Oliveto admits.
Before you start to panic, Oliveto argues -- and he has a good point -- the most conservative statistical analysis of Study 306B isn't necessarily the most appropriate analysis. Missing patient data from Study 306B will likely be a topic of discussion at the Jan. 14 panel but Chelsea has performed multiple statistical analyses and is confident that all demonstrate Northera's clinical benefit in this NOH patient population, he says.
Here's another Northera data slide of interest, showing a huge reduction in the number of falls experienced by NOH patients treated with Northera compared placebo. Preventing or reducing falls is obviously important to doctors and NOH patients, so Northera's ability to reduce falls is a positive.