Two Steps Forward for Clearside’s SCS Suprachoroidal Platform

The novel platform Clearside Biomedical is developing for delivering drugs to the back of the eye has taken two steps forward in recent weeks, with the release of encouraging safety results from its neovascular age-related macular degeneration (nAMD) program, and the issuance of a Food and Drug Administration action date for the injectable steroid it’s developing with Bausch + Lomb for the treatment of uveitis.

By the time the American Academy of Ophthalmology meets in New Orleans in November, the FDA is highly likely to have approved the uveitis indication.

Wall Street has taken notice. Since the announcements, Clearside’s stock price has jumped by 62%, closing at $4.89 last Friday.

Clearside and B+L reported that the FDA accepted their joint, resubmitted New Drug Application (NDA) for Xipere, the triamcinolone acetonide injectable suspension for treatment of uveitis-associated macular edema. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of October 30. It would be the first approval of Clearside’s novel platform that uses the patented SCS Microinjector to deliver drug directly into the choroid.

Suprachoroidal Delivery
The choroid is the cellular layer that lies between the sclera – the outer lining, or “white,” of the eye – and the optical part of the retina. Drug delivered directly to the choroid has the potential to penetrate the adjacent retina with a greater degree of bioavailability than intravitreal injection, the primary method for delivering drugs to the retina whereby the drug is injected into the vitreous, where it disperses before reaching the retina.

Targeted drug delivery via the suprachoroidal space may also limit corticosteroid exposure to the anterior segment with the potential to reduce the risk of cataracts, intraocular pressure rise, and worsening of glaucoma that commonly occur after injection of corticosteroids into the eye.

“Clearside’s innovative, suprachoroidal approach to ophthalmic drug delivery could be a major breakthrough for the treatment of retinal diseases, as it demonstrates the potential for a reliable, non-surgical, office-based method to deliver a variety of therapeutic products behind the retina outside of the visual field for a broad range of back of the eye diseases,” Thomas A. Ciulla, MD, MBA, CMO, and chief development officer of Clearside, said in exclusive comments to OIS Weekly.

Xipere Clinical Trials
Dr. Ciulla noted the pivotal Phase III PEACHTREE trial for Xipere was the first uveitis trial to utilize change in visual acuity as a primary endpoint, and, if approved, Xipere will be the first commercial product for the treatment of macular edema associated with uveitis.

“The approval of Xipere will further validate our proprietary suprachoroidal injection platform and its utility to deliver therapeutics into the suprachoroidal space,” Dr. Ciulla said.

Clearside president and CEO George Lasezkay, PharmD, credited the relationship with B+L for advancing the commercialization of the SCS platform, calling B+L “an outstanding global partner.”

Dr. Lasezkay added, “We maintain an ongoing dialogue with Bausch Health and Bausch + Lomb, and they provided input and support in connection with the recent NDA resubmission.” Clearside’s medical affairs, supply chain, and clinical teams have worked closely with the Bausch Health and B+L teams as they prepare for the commercial launch of Xipere in the US, he said.

AMD Indication
Shortly after announcing the Xipere breakthrough, Clearside reported positive safety results from Cohort 1 of OASIS, its ongoing Phase I/IIa clinical trial of CLS-AX, an injectable suspension of the small-molecule tyrosine kinase inhibitor axitinib, an agent commonly used to treat renal cell carcinoma.

CLS-AX was administered by suprachoroidal injection via the SCS Microinjector in six patients with nAMD. The primary endpoints were achieved in Cohort 1, as the initial lowest planned dose of 0.03 mg CLS-AX was well tolerated with no serious adverse events and no drug-related treatment emergent adverse events observed throughout the study period. There were no signs of inflammation, no vasculitis, no intraocular pressure safety signals, no dispersion of drug into the vitreous, or any other drug-related adverse events.

The OASIS Safety Monitoring Committee has reviewed the data and the trial will advance to Cohort 2, for which Clearside expects to begin patient screening for a 0.1-mg dose this month. Completion of the four-month study is expected by the end of the year.

Clearside’s Pipeline
The SCS platform is the foundation of Clearside’s robust pipeline. A separate Xipere program with Arctic Vision for use in Greater China and South Korea is in a Phase II trial. Clearside also has a preclinical program of the SCS platform in diabetic macular edema.

Clearside has partnerships with two other companies developing novel treatments for back-of-the-eye diseases. Last year the company and partner Aura Biosciences reported dosing the first patient in the Phase II trial of AU-011 for primary choroidal melanoma – an ocular cancer for which enucleation, or removal of the eye, is the current typical treatment.

In 2019 Clearside entered into an agreement to license its SCS Microinjector platform to REGENXBIO for delivery of adeno-associated virus (AAV)-based therapies, including RGX-314 for the treatment of nAMD and diabetic retinopathy.