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A dropless option for steroid therapy showed encouraging results in a phase II safety and efficacy study in patients with inflammatory dry eye disease.
Reviewed by John D. Sheppard, MD
Norfolk, VA-OTX-DP, a sustained-release dexamethasone 0.4 mg intracanalicular depot (Dextenza, Ocular Therapeutix), showed promise when compared with placebo in an exploratory phase II study in subjects with signs and symptoms of inflammatory dry eye disease, said John D. Sheppard, MD.
“We have a very exciting prospect for eventual approval based on the initial data of both safety and efficacy and the possibility of achieving improvement in both the signs and symptoms of dry eye,” said Dr. Sheppard, Virginia Eye Consultants, Norfolk.
“You now have a device that’s also a medication and vice versa, a well-established drug and a well-established device in combination,” he added. “By providing that appropriate synergy, we’re hoping that the medication concentration and the decay profile of that particular plug are ideally suited to dry eye.”
Overall, the polyethylene glycol-based hydrogel drug product was safe and well tolerated. While the study was not powered for statistical significance, the results showed that total corneal fluorescein staining scores at day 30 were significantly lower (p = 0.08) for eyes treated with the OTX-DP (-3.14) than in the placebo vehicle group (-1.10) when compared to baseline.
In addition, the onset of action on inferior corneal staining was observed as early as 2 weeks after treatment began and was confirmed through 4 weeks.
In the analysis of symptoms, OTX-DP was statistically superior to placebo vehicle for itching at day 15 based on Visual Analog Scale (VAS) scores. OTX-DP was also statistically superior to the placebo vehicle for severity at day 15 based on results of the Standard Patient Evaluation of Eye Dryness (SPEED). No difference was noted between the OTX-DP and placebo in results of the Ocular Discomfort Scale (ODS), while results of the Ocular Surface Disease Index (OSDI) were inconclusive.
The double-masked study was conducted at 2 sites; 42 patients were randomly assigned 1:1 to either OXT-DP or placebo vehicle inserted in the vertical canaliculus bilaterally following a 45-day phase of treatment with only the placebo vehicle.
They underwent treatment for 30 days with follow-up at post-insertion days 3, 15, and 30. The primary effectiveness analysis measures included a comparison of corneal fluorescein staining and conjunctival lissamine green staining between the device and placebo. Further comparisons were made using slit lamp assessments, Schirmer testing, and subject-reported scores on the ODS, OSDI, VAS, and SPEED tools.
Because of the small number of subjects enrolled, investigators used a p value of 0.1 rather than 0.5.
“We had significance to 0.1 for signs and symptoms, which was very encouraging and very likely to promise equally encouraging results at a higher significance for a larger cohort in further trials,” Dr. Sheppard said.
The strategy behind the OTX-DP is to combine two of the most important treatments for patients with dry eye: tear conservation and topical anti-inflammatory therapy. Tear conservation is typically addressed with punctal occlusion, while topical agents, such as corticosteroids, lifitegrast, or cyclosporine are often highly effective at reducing inflammation.
However, compliance issues such as frequent dosing, prescription refills, arthritis, tremors, and affordability can influence the efficacy of topical agents, Dr. Sheppard said.
He also noted that drops placed in the eye quickly dissipate, becoming reduced to 3% to 6% of the initial concentration within 5 to 10 minutes.
While a drop is at a high therapeutic level for only a short time after installation, a sustained release delivery system provides a low but constant level of drug delivery over a longer period and what is believed to be superior pharmacokinetics and thus a greater area under the curve, Dr. Sheppard explained.
“The cumulative dosage is likely to be much higher with the sustained release delivery system and therefore safer too because you don’t get such a high a concentration spike of the medicine,” he added. “That’s a really exciting prospect because you can optimize both therapies (reduction of inflammation and tear conservation) with the dexamethasone plug.”
In addition, giving the drug at a low concentration over a long period of time should produce a lower level of side effects.
A phase III study is being planned and discussed with appropriate agencies and consultants.
John D. Sheppard, MD
This article was adapted from Dr. Sheppard’s presentation at the 2016 meeting of the American Society of Cataract and Refractive Surgery. Dr. Sheppard is a consultant, speaker, and clinical researcher for Ocular Therapeutix.