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    Injectable sustained release drug delivery shows promise

    Take-Home

    An injectable intraocular sustained release drug delivery system demonstrated favorable safety and efficacy results in a multicenter phase II clinical trial.

    Dr. Chang

    Los Altos, CA—A sustained release intraocular drug delivery post-cataract surgery is one step closer to becoming a reality with the completion of a dose ranging trial of a novel biodegradable form of injectable dexamethasone, said David F. Chang, MD.

    More than half of the patients in the trial showed complete anterior chamber cell clearing by day 8 following routine cataract surgery with good safety results.

    “These are very promising results,” said Dr. Chang. clinical professor at the University of California, San Francisco, and private practice in Los Altos, CA. “We can—with a single application of drug administered into the anterior chamber at the conclusion of intraocular surgery—get dosing that appears to be safe and efficacious in the context of this trial.

    “The next step is a larger trial. Every ophthalmologist would love to have this kind of sustained release drug delivery if, indeed, it works,” he said.

    Examining the drug

    A bioabsorbable injectable drug delivery system (IBI-10090, ICON bioscience) is designed for short-term delivery of therapeutic levels of dexamethasone within the eye.

    A small droplet—5 µl—is injected into the eye following surgery and forms a surface tension-based sphere. The drug is released into the eye as the droplet is absorbed, providing controlled delivery directly to the target tissue for 11 to 21 days, depending on the formulation. When the drug depot is fully absorbed, drug delivery stops.

    “I believe that the next major advances in the field of ocular anti-inflammatory pharmacology will be in terms of drug delivery,” Dr. Chang said. “We are still limited, in most patients, to using anti-inflammatory eye drops with all the attendant disadvantages. The advantage of a sustained release delivery system is that it relieves the patient of the responsibility and inconvenience of instilling eye drops. It simplifies their life while at the same time more effectively delivering medication to the target tissue without systemic exposure.

    “This intraocular delivery system gives you continuous high levels of drug rather than the variable peaks and troughs that occur with intermittent dosing and it completely eliminates the issue of corneal penetration,” he said.

    About the trial

    Surgeons at 13 centers across the country enrolled 172 patients for this post-cataract surgery inflammation trial. Patients were randomly assigned to one of three doses: 342 µg sustained-release dexamethasone (58 patients), 517 µg (56 patients), or 697 µg (58 patients).

    Each patient received a single injection of 5 µl of the drug, delivered through a 25-gauge cannula directed behind the iris. The injection forms a visible sphere that is absorbed over time.

    Patients in the trial had to be:

    ·      Forty years or older

    ·      Undergoing a unilateral phacoemulsification

    ·      Best-corrected visual acuity between 20/30 and 20/200

    ·      A visual potential greater than 20/30 in the study eye

    ·      A baseline endothelial cell count of 2000 cells/mm2 or greater.

    Patients were excluded if they had a recent history of ocular, topical, or oral steroids or NSAIDS or had received any intravitreal sustained-release drug delivery.

    The primary efficacy endpoint was anterior chamber cells (ACC), graded as a score of 0 (cells absent) to 4 (hypopyon), assessed by slit lamp biomicroscopy. The safety analysis was based on both ocular and non-ocular adverse events for the first 90 days following surgery.

    The mean age of patients in the trial was about 70 and the majority of patients were female.

    The sustained release delivery was clearly successful, Dr. Chang said.

    Study results

    VIDEOOOOO

    At day 8 postop, 53.4% of patients in the 342-µg group had complete ACC clearing, 51.8% of the 517-µg group, and 63.8% of the 697-µg group. While there were numerical differences in ACC between the three dosage groups, there was no statistically significant difference between them (p > 0.50).

    Overall, 94% of all patients had ACC scores of 0-1 (1 – 5 cells) by 8 days.

    “This study measured the number of patients with complete clearing of AC cells following uncomplicated cataract surgery, and followed the design of other FDA clinical trials for anti-inflammatory medication” Dr. Chang said. “For example, using difluprednate, 22% of patients had zero AC cells by day 8; with bromfenac it was 24%.

    If this is a safe and effective way to deliver medication without eye drops, sustained release could be especially useful for higher risk eyes that are more prone to inflammation,” he said.

    “As a surgeon, you know the eye will get the proper medication dosing with a sustained release intraocular delivery system,” Dr. Chang continued. “In addition, there is a significant reduction in the chair time and staff time that comes with prescribing topical meds and reviewing the instructions with patients and family members. This system would be a win-win for patients and ophthalmologists alike.”

    David F. Chang, MD

    E: [email protected]

    Dr. Chang disclosed stock options in ICON Bioscience.

     

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