Bausch + Lomb’s Xipere therapy offers hope to patients with macular edema associated with non-infectious uveitis.

More than 300,000 people in the United States have non-infectious uveitis — approximately 80% of which is anterior and 20% is posterior.¹ Macular edema, the leading cause of vision loss in patients with uveitis,² is present in approximately 10% of the anterior market and 50% of the posterior market.³

Until recently, the FDA had not approved any treatments for patients with macular edema associated with non-infectious uveitis. But that changed when Bausch + Lomb’s Xipere (triamcinolone acetonide injectable suspension) 40mg/mL was approved by the FDA in October 2021 as the first and only therapy indicated for this condition.

“Given macular edema is the leading cause of vision loss in patients with uveitis, we believe that Xipere will provide eye-care professionals with a promising new treatment option for their patients with uveitic macular edema,” says Yolande Barnard, VP and general manager of US Pharmaceuticals at Bausch + Lomb. An affiliate of Bausch Health acquired the exclusive license for the commercialization and development of Xipere in the United States and Canada in October 2019.

TARGETED DRUG DELIVERY

Xipere offers another novelty — it’s the only FDA-approved therapy that uses the suprachoroidal space (located between the choroid and the outer protective layer of the eye, in the sclera) for drug delivery. With its approval, the suprachoroidal space, which was once considered a potential space only visible under pathologic conditions, is now recognized as an alternative administration route, Ms. Barnard says.

“Suprachoroidal injection enables medicine to be rapidly and adequately dispersed to the back of the eye, offering the potential for the medicine to act longer and minimize harm to the surrounding healthy parts of the eye,” she says.

Targeted drug delivery via the suprachoroidal space may also limit corticosteroid exposure to the anterior segment, Ms. Barnard says, with the potential to decrease adverse events such as cataracts, IOP elevation and exacerbation of glaucoma, which are commonly associated with local corticosteroid delivery techniques.

“Because of the highly targeted approach, there is the potential for increased efficacy while reducing safety concerns,” adds Steven Yeh, MD, professor of ophthalmology and director of retinal disease and uveitis at the Stanley M. Truhlsen Eye Institute at University of Nebraska Medical Center in Omaha. “The suprachoroidal space is highly compartmentalized; Xipere targets the posterior segment tissues — the retina and choroid — which are most relevant for care.”

Pre-clinical studies of Xipere have shown high levels of medications delivered to posterior segment tissues, including the retina, with limited pharmacokinetic effects on anterior segment structures.^4,5

PROMISING CLINICAL STUDY RESULTS

Multiple clinical studies have demonstrated Xipere’s safety and efficacy.^4,5 “Xipere’s unique suprachoroidal administration approach provides exceptional access and high bioavailability to the posterior segment of the eye,” Dr. Yeh says.

The PEACHTREE study,⁶ a Phase 3 trial that sought to understand the medication’s effectiveness and safety for patients with macular edema due to non-infectious uveitis, showed that nearly 50% of patients who received Xipere had three lines or greater of visual acuity benefit. Patients started seeing visual acuity benefits by week four, with continued improvement by the week 24 primary endpoint, says Dr. Yeh, who was the principal investigator for Phase 3 of the study. Continued improvement, including reduction of macular edema, was also observed at week four with sustained effects at the week 24 time point. OCT confirmed the anatomic improvements.

Other metrics of inflammation, including anterior chamber inflammation and vitreous inflammation, were also reduced with suprachoroidal drug delivery for patients with macular edema due to non-infectious uveitis, Dr. Yeh says.

Xipere was well tolerated by clinical trial patients.^4-6 The most common adverse reactions reported by approximately 10% of patients included elevated IOP and eye pain.^4-6

The subsequent MAGNOLIA extension study⁴ looked at drug durability. Approximately 50% of patients who were administered Xipere in the PEACHTREE study were followed for an additional 24 weeks. They didn’t require any additional rescue therapy.

Xipere is contraindicated in patients with infectious uveitis or active or suspected ocular or periocular infections, including most viral diseases of the cornea and conjunctiva. It is also contraindicated in patients with known hypersensitivity to triamcinolone acetonide or any other components of the product.⁷

PAVING THE WAY

Xipere’s FDA approval opened the door to explore using the suprachoroidal space for drug delivery for other serious eye diseases. “I’m excited about the potential to treat other diseases in the retina and posterior segment,” Dr. Yeh says.

“The suprachoroidal space is an untapped frontier in eye health,” says George Lasezkay, PharmD, JD, president and CEO of Clearside Biomedical. Xipere is designed for suprachoroidal administration via Clearside’s SCS Microinjector. “We’re proud to be the pioneers in treating serious retinal diseases by implementing this novel, targeted approach. With this approval, we begin a new era in delivering therapies to the back of the eye.”

Bausch + Lomb plans to make Xipere available as a new treatment option for patients in the first quarter of 2022. OM

REFERENCES

1. Thorne JE, Suhler E, Skup M, et al. Prevalence of Noninfectious Uveitis in the United States: A Claims-Based Analysis. JAMA Ophthalmol. 2016;134:1237-1245.
2. Massa H, Pipis SY, Adewoyin T, et al. Macular edema associated with non-infectious uveitis: pathophysiology, etiology, prevalence, impact and management challenges. Clin Ophthalmol. 2019;13:1761-1777. Published 2019 Sep 10.
3. Lardenoye CW, van Kooij B, Rothova A. Impact of macular edema on visual acuity in uveitis. Ophthalmology. 2006;113:1446-1449.
4. Khurana RN, Merrill P, Yeh S, et al. Extension study of the safety and efficacy of CLS-TA for treatment of macular oedema associated with non-infectious uveitis (MAGNOLIA) [published online ahead of print, 2021 Mar 12]. Br J Ophthalmol. 2021;bjophthalmol-2020-317560.
5. Henry CR, Shah M, Barakat MR, et al. Suprachoroidal CLS-TA for non-infectious uveitis: an open-label, safety trial (AZALEA) [published online ahead of print, 2021 Feb 5]. Br J Ophthalmol. 2021;bjophthalmol-2020-318019.
6. Yeh S, Khurana RN, Shah M, et al. Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial. Ophthalmology. 2020;127(7):948-955.
7. Xipere [prescribing information]. Alpharetta, Ga.: Clearside Biomedical, Inc.; 2021.