ISTA Pharmaceuticals Inc. announced it has received a non-approvable letter from the FDA relating to
its new drug application (NDA) for prednisolone acetate 1% and tobramycin 0.3% ophthalmic suspension
(T-Pred). The product is being developed as a topical steroid to treat inflammatory ocular conditions
for which a corticosteroid is indicated and where bacterial ocular infections or a risk of bacterial
"While we are disappointed by the FDA's decision, ISTA is committed to bringing T-Pred to
ophthalmologists and patients," said Vicente Anido Jr., PhD, president and chief executive officer of
ISTA Pharmaceuticals. "We believe our clinical study met the endpoints that ISTA and the FDA agreed
to in the special protocol assessment.
"Nonetheless, the FDA did not find sufficient clinical information to merit approval," Dr. Anido
added. "We plan to work closely with the agency to resolve this issue in an efficient manner. We
intend to request a meeting with the agency to come to agreement on the actions ISTA Pharmaceuticals
must undertake to receive marketing approval for T-Pred."
In the fourth quarter of 2005, ISTA Pharmaceuticals completed its phase III clinical study of
prednisolone acetate 1.0% and tobramycin 0.3% ophthalmic suspension. The study was designed as a
multicenter, randomized, double-blind study to determine the bioequivalence of prednisolone
concentrations between prednisolone acetate 1% and tobramycin 0.3% ophthalmic suspension and
prednisolone acetate 1% (Pred Forte, Allergan). ISTA believes its study demonstrated T-Pred achieved or exceeded
this goal both in the intent-to-treat and the per-protocol patient populations. In addition, the
company said its studies showed T-Pred to have antimicrobial activity equivalent to other combination
products approved for this indication.
The FDA assessed the company's clinical data as not showing sufficient equivalence between the
prednisolone component in T-Pred and PredForte at least at one of the time points measured nor
equivalence in the kill time between the tobramycin components in T-Pred and Tobrex (Alcon
Laboratories), although it showed equivalence versus loteprednol etabonate 0.5% and tobramycin 0.3%
ophthalmic suspension (Zylet, Bausch & Lomb) and tobramycin 0.3% and dexamethasone 0.1% sterile
ophthalmic suspension and ointment (TobraDex, Alcon Laboratories), according to ISTA Pharmaceuticals
in a prepared statement.
The company said it plans to request a meeting with the FDA as quickly as possible.