Rapamycin safe for treating DME, finds phase I trial

A phase I trial of rapamycin (Sirolimus, Wyeth) indicated thatthe drug is safe and has biologic activity against diabeticmacular edema (DME), according to Mark Blumenkranz, MD.

A total of 50 patients with DME were included in thisprospective, randomized, dose-escalation trial. The patientsreceived either one intravitreal injection or one subconjunctivalinjection. For the 25 patients in the intravitreal group, thedoses ranged from 44 to 352 µg, and for the 25 patients in thesubconjunctival group the doses ranged from 220 to 1,760µg. The baseline demographics of the two groups weresimilar.

The investigators found no significant systemic exposure torapamycin. Dr. Blumenkranz reported that the drug was relativelywell tolerated and there was no dose-limiting toxicityencountered. There were five serious adverse events (vitreoushemorrhages and epiretinal membranes), none of which wasconsidered by the investigators to be related to the drugitself.

"Importantly, there was no progression in cataract and there wasno increase in IOP levels aside from the transient IOP increasesthat occur immediately following the injection," Dr. Blumenkranzsaid.

Both routes of administration were found to be effective. Thevisual acuity increased a mean of five letters in both groups byday 90 after treatment that was accompanied by a decrease in themacular thickness seen on optical coherence tomography scanning.The group that received the subconjunctival injection hadslightly better efficacy; with the two lowest doses (220 and 440µg), the investigators found a mean visual acuity increaseof about six letters, according to Dr. Blumenkranz.

"The formulation of rapamycin designed for ocular use, bothintraocularly and subconjunctivally, was judged to be safe as theresult of the absence of serious adverse events related to thedrug," Dr. Blumenkranz said. "There appeared to be preliminaryefficacy signals, although this study was not designed to showefficacy. The drug is moving into a phase II trial for patientswith DME and age-related macular degeneration."