Split FDA Panel Favors Droxidopa for Hypotension
released before the meeting had recommended against approval, citing lack of evidence that the drug is effective for longer than four weeks and "worrisome safety signals" seen in clinical trials.
The latter included deaths, strokes, heart attacks, hypertensive crises, and underlying disease progression that occurred during the open-label phases of the trials.
Also, nine cases of neuroleptic malignant syndrome had been seen in Japanese patients taking the drug.
Droxidopa is being developed by Chelsea Therapeutics for treating symptomatic, neurogenic orthostatic hypotension in patients with primary autonomic failure -- which can be associated with Parkinson's disease and multiple system atrophy -- dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.
Currently, the only drug specifically approved for this indication is midodrine, and the FDA may soon pull it from the market because it has never been shown to be effective in rigorous trials.
A variety of other drugs are used off-label, all of which have significant side effects and/or contraindications.
Droxidopa is a prodrug for norepinephrine, converted both peripherally and centrally as it crosses the blood-brain barrier.
It therefore acts as a vasoconstrictor which, at least in theory, should help patients retain adequate blood pressure when they stand up from sitting or supine positions.
Chelsea's marketing application was based largely on two randomized trials and an open-label extension to one of them.
One of the randomized studies failed to meet its primary efficacy endpoint, which the FDA staff review noted among the drug's negatives.
A recent study confirmed that treatment with antibiotics -- or at least amoxicillin -- is of .