OR WAIT null SECS
Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.
FA implant effective in lowering recurrence rates through available 6, 12 months of follow-up
A new fluocinolone acetonide intravitreal implant (Yutiq, EyePoint Pharmaceuticals) that is expected to release a fixed-corticosteroid dose for 3 years is now commercially available for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye.
Reviewed by David Callanan, MD
Following the FDA approval of the fluocinolone acetonide (FA) 0.18 mg intravitreal implant (Yutiq, EyePoint Pharmaceuticals) for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye in October 2018, the product was launched for commercial use in February 2019.
According to uveitis specialist, David Callanan, MD, access to the sustained-release corticosteroid implant is a welcome development because it provides clinicians with another great tool for treating appropriately selected patients affected by this sight-threatening disease.
“Every uveitis patient with posterior uveitis is unique, and individuals may respond differently to different medications,” said Dr. Callanan, partner, Texas Retina Associates, and clinical professor of ophthalmology, University of Texas Southwestern Medical School, Dallas.
“Locally administered corticosteroids, however, are generally very effective, and the ability to treat locally is important, especially for avoiding exposure to toxicities of systemic medications in patients who do not have associated extraocular findings or for those whose uveitis is not responding adequately to systemic immunomodulatory therapy.”
“Phase III study results demonstrate that the new FA implant was effective for lowering recurrence rates through the available 6 and 12 months of follow-up, and the safety data on IOP elevation are encouraging so far,” he said. “The trials are ongoing, and we look forward to longer-term findings.”
The new FA implant uses a non-bioerodible, micro-insert platform that is designed to release a daily FA dose of 0.25 mcg over 3 years. The micro-insert is injected into the vitreous through the pars plana using a preloaded sterile applicator fitted with a 25-gauge needle. The injection is done in an in-office procedure akin to that used for intravitreal injections of anti-VEGF medications or dexamethasone 0.7 mg intravitreal implant (Ozurdex, Allergan).
“Unlike the previously available FA 0.59 mg implant (Retisert, Bausch + Lomb), intravitreal placement of the new FA product does not have to be done in the operating room,” Dr. Callanan said. “Compared with the dexamethasone implant, the new FA implant is longer acting and therefore holds promise for maintaining remission with fewer re-injections.”
“Although the benefit of the dexamethasone implant (Ozurdex, Allergan) persisted for about 6 months in its pivotal clinical trial, clinical experience shows that efficacy can be lost after 3 months in quite a few patients,” he said. “Our aim in treating uveitis is to maintain quiescence and eliminate repeated flares that can lead to permanent tissue damage and achieving that goal with the dexamethasone implant may carry a relatively high injection burden for some patients.”
Clinical trial results
In two phase III trials, patients with non-infectious posterior uveitis were randomly assigned to treatment with the FA 0.18 mg implant or sham injection.
Eligible patients had been affected by posterior uveitis for at least 1 year and experienced at least 2 separate recurrences requiring treatment with systemic medication (corticosteroid or immunosuppressive medications) or local corticosteroid injections (intraocular or periocular) or had received systemic therapy for at least 3 months or at least 2 local corticosteroid injections during the previous 12 months.
The rate of recurrent uveitis flares at month 6 was analyzed as the primary endpoint and was significantly lower (p < 0.01) in both studies in the FA group compared with the control group (18.4% versus 78.6% and 21.8% versus 53.8%).
A statistically significant difference (p < 0.01) in the recurrence rate favoring the FA implant group over the control group was also achieved at month 12 (27.6% versus 85.7% and 32.7% versus 59.6%) (p < 0.01 for all comparisons of FA versus sham).
“Based on the statistical plan that was designed for trial robustness, patients who missed the 6-month follow-up visit were counted as having a recurrence, and for that reason, the recurrence rates in the FA group may be artificially high,” Dr. Callanan said.
The safety review for data collected through 12 months showed that the mean IOP increase was 1.3 mm Hg in the FA implant group and 0.2 mm Hg for the controls in one study and 2.0 mm Hg for the FA implant group and 0.0 mm Hg in the control group in the other trial.
In a pooled analysis, the percentages of patients requiring any IOP-lowering medication and undergoing surgery for elevated IOP were similar in the FA implant and control groups. Rates of cataract surgery in the two studies were 33.3% and 18.0% in the FA implant group and 4.8 and 8.6% for the control group.
“The prescribing information for the FA 0.59 mg implant (Retisert) notes that based on clinical trial data, about 77% of patients will require IOP-lowering medications and 37% of patients will require glaucoma filtering surgery within 3 years after implantation,” he said.
Early data with the new FA implant suggests IOP elevation may be a less significant issue. A possible explanation for the difference may be that the older FA implant is surgically sewn into the pars plana close to the crystalline lens and ciliary processes.
The new FA implant (Yutiq) is also a lower dose than the previous 0.59 FA implant (Retisert), he added. Dr. Callanan noted the minute size of the implant probably explains why the majority of patients do not seem to be aware of its presence in the eye.
Dr. Callanan said that the ideal candidate for treatment with the new FA implant is a pseudophakic patient with chronic non-infectious posterior uveitis who has demonstrated a therapeutic response to prior local corticosteroid treatment without significant IOP.
David Callanan, MD
Dr. Callanan is an investigator in one of the phase III FA 0.18 mg implant clinical trials and is a consultant to EyePoint Pharmaceuticals.