Recurrent inflammatory flare-ups characterize the chronic nature of noninfectious posterior uveitis. Repeated courses of corticosteroids have been the therapy of choice, but they are associated with well-documented ocular side effects, namely increased intraocular pressure and cataract formation.
The need for a treatment that provides effective and continuous control of the disease with an acceptable safety profile has set off a scramble to develop longer-term drug-treatment platforms that include surgical implants and injectable inserts. At the Association for Research in Vision and Ophthalmology last month, investigators reported successful top-line 12-month data from a three-year fluocinolone acetonide (FA) insert (Durasert, pSivida Corporation) for the treatment of chronic noninfectious posterior uveitis.1
The lower doses of FA that the insert delivers may avert the problems of prolonged oral therapy and repeated steroid injections for recurrent noninfectious uveitis, says Dario Paggiarino, MD, vice president and chief medical officer of pSivida.
Twelve-month data from the first of two three-year, Phase III trials showed a reduction of recurrence and modest rises in intraocular pressure. Recurrence rates were 27.6 percent for the treatment group vs. 85.7 percent for sham in the intention to treat population (p<0.001). The sham group was also more likely to use adjunctive therapy at 12 months; 61.9 percent required intra- or periocular steroids vs. 6.9 percent of the insert group. The trial involves 129 subjects randomized to the insert and sham.
Here, Dr. Paggiarino answers key questions about the insert.
How does the insert work?
The insert is administered through a single intravitreal injection in the office and delivers micro-doses ranging from 0.13 to 0.15 μg of FA daily over three years, which is significantly longer than currently approved intravitreally injected treatments. This modality may be ideal to address the chronic and recurrent nature of the condition. Avoiding disease flares is important because they can cause irreversible damage to the neuroretina.
What’s the key take-home from the first Phase III trial?
The 12-month data showed the insert continued the reduction in disease recurrence previously reported with the six-month data. From a safety standpoint, we did observe the typical steroid effect, but because of micro-dosing the increase in IOP on average is modest compared to sham—1.3 mmHg vs. 0.2 mmHg in the sham group. Overall the effect on IOP as a result of a single insert injection seems to be modest and also fairly predictable, stable and manageable over 12 months. The percentages of patients who required IOP-lowering therapy at 12 months were almost identical: 26.4 percent for the insert group and 26.2 percent for sham.
With regards to cataract, of the phakic patients at study entry 33.3 percent in the treatment group needed surgery vs. 4.8 percent in the sham group. However, about half of the study population was already pseudophakic at entry.
What’s the big question that the three-year results should answer?
The 12-month data is very encouraging, and the question becomes what is the long-term effect of micro-dosing of FA in terms of maintaining patients recurrence-free, limiting the number of recurrences, and, of course, the long-term safety profile.
The second of the two Phase III studies is expected to read out this month. Pending its findings, a New Drug Application in the United States should be filed by the end of the year. Also, this insert technology has other potential applications beyond noninfectious posterior uveitis and even beyond ophthalmology. RS
1. Jaffe GJ, Paggiarino DA, Riedel GE. An injectable fluocinolone acetonide intravitreal insert decreases the incidence of recurrence in patients with chronic non-infectious uveitis affecting the posterior segment of the eye: 12-month results. Paper presented at: Association for Research in Vision and Ophthalmology 2017; May 8, 2017; Baltimore, MD.