FDA approves XIPERE injection for treatment of uveitic macular edema

On October 25, 2021, Bausch + Lomb and Clearside Biomedical announced that the US FDA granted approval to triamcinolone acetonide injectable suspension (XIPERE) for suprachoroidal use for the treatment of macular edema associated with uveitis.

Formerly known as CLS-TA, the novel product represents the first ever treatment approved by the FDA for injection into the suprachoroidal space. The product is a proprietary preservative-free formulation of triamcinolone acetonide (TA), and the injection is performed as an in-office procedure using a proprietary syringe and needle platform (SCS Microinjector).

The approval by the FDA was based on results of PEACHTREE, a randomized, controlled, masked phase 3 clinical trial comparing treatment with two injections of suprachoroidal TA (weeks 0 and 12) or a sham procedure. PEACHTREE met its primary endpoint by showing statistical superiority of suprachoroidal TA versus sham for the percentage of eyes achieving a BCVA gain ≥15 ETDRS letters from baseline to week 24 (47% vs. 16%, P <.001). The study also met all secondary endpoints including reduction in macular edema and improvement in anterior chamber and vitreous inflammation and found that the investigational corticosteroid was safe and well-tolerated.

Data from MAGNOLIA, an extension study, showed that the treatment benefit of suprachoroidal TA could persist for at least 9 months in many patients.¹

Steven Yeh, MD

Steven Yeh, MD, is the first author of the published article reporting the PEACHTREE study² and is Professor of Ophthalmology at the Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha. He told Modern Retina, “The approval of XIPERE is an exciting advance in the care for patients with intraocular inflammation and macular edema associated with noninfectious uveitis. Corticosteroids are a mainstay of treatment for this condition, and XIPERE represents a new method of drug delivery that was well-tolerated, showed good safety, and had striking benefit for improving visual acuity and other efficacy measures.”

“PEACHTREE assessed visual acuity as the primary endpoint, which is an important point because of all of the measurable clinical features of uveitic macular edema, vision is the one that most affects quality of life for our patients.”

Dr. Yeh went on to explain that the efficacy and safety of suprachoroidal TA may be understood by its pharmacokinetics that show suprachoroidal delivery results in very compartmentalized distribution of the corticosteroid, targeting the pathology while limiting exposure to tissues that are adversely affected by corticosteroids.

“Findings from preclinical studies show that there is rapid dispersion of TA into the choroid and retina after suprachoroidal injection and persistence of high levels of the corticosteroid for more than 3 months. However, exposure of the anterior segment to the corticosteroid is limited,” he said.

“Therefore, suprachoroidal TA offers the potential for rapid and effective control of uveitic macular edema with the potential to limit corticosteroid-related complications of cataract, IOP elevation, and glaucoma exacerbation.”

The PEACHTREE pivotal trial

PEACHTREE randomized 160 patients 3:2 to treatment with triamcinolone 4 mg/0.1 mL or sham procedure. All anatomic subtypes of uveitis were represented in the study population. Approximately 50% of patients in the suprachoroidal TA arm and two-thirds of controls were phakic.

Mean time since uveitis diagnosis was 177 weeks in the suprachoroidal TA arm and 107 weeks in the control arm. Mean BCVA at baseline was approximately 55 letters in the suprachoroidal TA arm and 54 letters in the controls; and mean central subfield thickness (CST) in the two groups was 481 and 525 μm, respectively.

The secondary endpoint in PEACHTREE was mean change from baseline in CST measured by spectral-domain OCT at 24 weeks. Additional endpoints included mean change in BCVA in ETDRS letters by visit, mean change in CST by visit, and changes in signs of inflammation as evaluated by the Standardization of Uveitis Nomenclature scales.

Mean reduction in CST from baseline to week 24 was significantly greater in the suprachoroidal TA arm than the sham group (153 vs 18 μm, P <.001). Patients treated with suprachoroidal TA gained a mean of 9.6 ETDRS letters from baseline at week 4 and showed further improvement thereafter, reaching a mean gain of 13.8 ETDRS letters at week 24 compared to just 3.0 ETDRS letters in the control group (P < 0.001).

Rescue therapy was allowed beginning at week 4 if patients met prespecified criteria or were not improving. It was received by 13.5% of patients in the suprachoroidal TA arm and 72% of control patients.

Durable efficacy

Patients from PEACHTREE were eligible for participation in MAGNOLIA if they completed PEACHTREE without needing any rescue therapy. Of 46 patients originally randomized to suprachoroidal TA and 7 originally randomized to sham, 28 patients in the suprachoroidal TA group and 5 patients in the control group entered the extension study.

During the 24-week follow-up period in MAGNOLIA (48 weeks post-randomization and 36 weeks after the second injection), 11 of the 28 patients originally treated with TA received rescue therapy and 3 were withdrawn because of an adverse event. Thus, 14 of the 28 patients (50%) required no rescue therapy. Three of the seven patients who had been in the PEACHTREE control arm received rescue therapy and two others withdrew.

MAGNOLIA investigated median time to rescue treatment during the extension period as its primary endpoint and showed that it was significantly longer in the triamcinolone group than in the control arm, 257 days vs. 55.5 days. At the end of the study, patients originally treated with suprachoroidal TA had a mean BCVA gain from baseline (PEACHTREE entry) of 12.1 ETDRS letters and a mean CST reduction of 174.5 μm.

Safety review

No serious adverse events considered by the investigators to be related to treatment with suprachoroidal TA were recorded during PEACHTREE or MAGNOLIA. In PEACHTREE, the rate of elevated IOP pertaining to the corticosteroid (this analysis excludes events on the day of the procedure) was higher in the control group than in the triamcinolone arm (15.6% vs 11.5%) and the rate of cataract formation was only slightly higher in the triamcinolone group than among eyes receiving sham injection (7.3% vs 6.3%).

“It is important to note that in PEACHTREE, the suprachoroidal TA injection was well-tolerated and associated with a lower rate of elevated IOP than the sham control procedure where rescue therapies could be administered during the trial,” Dr. Yeh said.

Implementing the new corticosteroid platform

Dr. Yeh noted that all investigators participating in the premarketing clinical trials received special training for administering the injection.

“The procedure used for suprachoroidal TA injection is a nuanced technique. However, it is very reproducible, can be learned by any ophthalmologist who is comfortable administering intraocular injections, and is well-tolerated by patients,” he said.

Dr. Yeh is a consultant to Clearside Biomedical, Bausch + Lomb, Allergan, Regenxbio, Adverum Biotechnologies, and Buoy Health.

References

1. Khurana RN, et al. Br J Ophthalmol. 2021 Mar 12:bjophthalmol-2020-317560. doi: 10.1136/bjophthalmol-2020-317560. Epub ahead of print.

2. Yeh S, et al; PEACHTREE Study Investigators. Efficacy and safety of suprachoroidal CLS-TA for macular edema secondary to noninfectious uveitis: phase 3 randomized trial. Ophthalmology. 2020 Jul;127(7):948-955. doi: 10.1016/j.ophtha.2020.01.006.

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