Clearside Biomedical Announces Successful End-of-Phase 2 Meeting with the FDA and Alignment on Phase 3 Plans for Suprachoroidal CLS-AX in Wet AMD

Rhea-AI Summary

Clearside Biomedical (NASDAQ: CLSD) has announced successful End-of-Phase 2 meeting results with the FDA regarding CLS-AX for wet AMD treatment. The company received alignment on its Phase 3 program design for two concurrent non-inferiority pivotal trials.

The proposed Phase 3 trials will feature:

• ~450 treatment-naïve participants per trial (225 per arm)
• Comparison of CLS-AX (1 mg) to aflibercept (2 mg)
• Primary endpoint measuring average BCVA change from baseline at Week 52
• Flexible maintenance dosing of every 3 to 6 months

CLS-AX combines flexible dosing of a biologic with extended duration of a tyrosine kinase inhibitor, administered via suprachoroidal injection. The treatment targets the $12+ billion wet AMD market, offering potential advantages through its positive safety profile, extended duration, and proven re-dosing capability.

Positive

• FDA alignment on Phase 3 program design
• Targeting $12+ billion wet AMD market
• Flexible dosing schedule (3-6 months)
• Positive safety profile from previous trials
• Extended treatment duration potential

Negative

• Must prove non-inferiority to existing treatment
• Extended two-year safety data requirement
• Large trial size requiring ~900 total patients

Insights

Financial Analyst

Clearside Biomedical's successful End-of-Phase 2 meeting with the FDA represents a significant derisking event for their lead asset CLS-AX in wet AMD treatment. This regulatory alignment substantially reduces uncertainty around the development pathway and increases probability of eventual commercialization.

The advancement to Phase 3 trials positions Clearside to potentially capture market share in the $12+ billion wet AMD market, where current treatments often require frequent injections that burden patients and healthcare systems. CLS-AX's differentiated profile - combining extended duration of a TKI with flexible dosing schedules (every 3-6 months) - addresses a clear market need and could drive substantial adoption if approved.

The company's strategic decision to target treatment-naïve patients in Phase 3 trials is noteworthy, as it accelerates recruitment timelines and broadens the potential commercial patient population. The non-inferiority trial design comparing against aflibercept (Eylea) establishes a clear regulatory pathway using a validated comparator.

While this news doesn't guarantee approval, it significantly improves development visibility. Investors should monitor upcoming trial initiation timelines, enrollment rates, and the company's financial runway to support these pivotal studies, which will require substantial capital investment.

Ophthalmology Specialist

The FDA's alignment on Clearside's Phase 3 program for CLS-AX represents a promising development for wet AMD treatment. The administration via suprachoroidal injection using Clearside's proprietary SCS Microinjector® could offer meaningful delivery advantages over standard intravitreal injections used by current therapies.

The clinical value proposition centers on the flexible maintenance dosing of every 3-6 months, which would significantly reduce treatment burden compared to current standard-of-care anti-VEGF agents typically administered every 1-3 months. For patients with this chronic condition requiring lifelong management, reduced injection frequency directly correlates with improved compliance and quality of life.

The non-inferiority trial design against aflibercept is appropriate and pragmatic. The primary endpoint of best-corrected visual acuity at 52 weeks is the gold standard for wet AMD trials and will provide comprehensive efficacy data across multiple treatment cycles. The optimization of the study population with tight screening criteria will reduce statistical noise and increase the likelihood of demonstrating non-inferiority.

Particularly noteworthy is the focus on detailed re-dosing criteria to minimize rescue treatment, suggesting confidence in the durability of CLS-AX's effect. This combination of TKI pharmacology with a novel delivery method addresses the two greatest unmet needs in wet AMD management: treatment durability and delivery precision.

- CLS-AX Phase 3 Program Designed to Maximize Commercial Potential in Wet AMD -

- Flexible Dosing and Extended Duration would be Important Differentiators from Existing Approved Therapies and Other Tyrosine Kinase Inhibitors in Development -

ALPHARETTA, Ga., March 06, 2025 (GLOBE NEWSWIRE) -- Clearside Biomedical, Inc. (Nasdaq: CLSD) (“Clearside” or the “Company”), a biopharmaceutical company revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space (SCS^®), announced today the receipt of the formal meeting minutes from its recent End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) relating to CLS-AX (axitinib injectable suspension) for the treatment of neovascular age-related macular degeneration (wet AMD). CLS-AX combines the flexible dosing of a biologic with the longer duration of a tyrosine kinase inhibitor (TKI) and is administered via suprachoroidal injection utilizing Clearside’s patented SCS Microinjector^®.

“We are pleased to report the positive outcome of our End-of-Phase 2 meeting with the FDA,” said George Lasezkay, PharmD, JD, President and Chief Executive Officer. “With a positive safety profile, extended duration, and proven re-dosing capability, CLS-AX has the potential to provide a compelling alternative in the $12+ billion wet AMD market. We look forward to highlighting our proposed Phase 3 program during our upcoming earnings call later this month.”

Victor Chong, MD, MBA, Chief Medical Officer and EVP, Head of Research and Development, commented, “Our interactions with the FDA have been very positive and productive and we are aligned on our proposed Phase 3 program. Recognizing that wet AMD patients require individualized treatment schedules, our proposed Phase 3 trials are designed to support a flexible maintenance dosing label of CLS-AX for every 3 to 6 months as needed based on patient disease assessments by the physician.”

The meeting and formal minutes confirmed key elements for two proposed Phase 3, non-inferiority, pivotal trials, including agreement on the protocol design, patient population, primary and secondary endpoints, and use of sham injections.

CLS-AX Proposed Phase 3 Program Highlights:

• Two concurrent, pivotal non-inferiority trials with a primary study endpoint of average change in best corrected visual acuity (BCVA) from baseline at Week 52, which ensures participants receive multiple doses of CLS-AX;
• Each trial will have two arms with ~225 participants per arm comparing CLS-AX (1 mg) to aflibercept (2 mg);
• Enrollment of treatment naïve participants, which represents a broader set of the general wet AMD population and enables quicker recruitment;
• Optimization of study population to reduce variability by using tight screening criteria and eliminating participants with highly variable visual acuity prior to randomization;
• Use of detailed re-dosing criteria for CLS-AX to minimize need for rescue treatment; and
• One-year safety follow up period to meet the registration requirement to submit two years of safety data.

About CLS-AX (axitinib injectable suspension)

Clearside is developing CLS-AX as a longer-acting therapy for the treatment of retinal diseases. CLS-AX (axitinib injectable suspension) is a proprietary suspension of axitinib for suprachoroidal injection. Axitinib is a tyrosine kinase inhibitor (TKI), currently approved as an oral tablet formulation to treat advanced renal cell carcinoma, that achieves pan-VEGF blockade, directly inhibiting VEGF receptors-1, -2, and -3 with high potency and specificity. Clearside believes this broad VEGF blockade may have efficacy advantages over existing retinal therapies by acting at a different level of the angiogenesis cascade and may benefit patients who sub-optimally respond to current, more narrowly focused anti-VEGF therapies. Suprachoroidal injection of this proprietary suspension of axitinib has demonstrated meaningful potential in Phase 1/2a and Phase 2b wet AMD clinical trials in which CLS-AX was well tolerated and demonstrated a positive safety profile. With suprachoroidal administration of axitinib, there is the potential to achieve prolonged duration and targeted delivery to affected tissue layers by compartmentalizing axitinib behind the retina, thereby limiting drug exposure to the front of the eye.

About Clearside’s Suprachoroidal Space (SCS^®) Injection Platform and SCS Microinjector^®

Clearside’s patent protected, proprietary suprachoroidal space (SCS^®) injection treatment approach offers unprecedented access to the back of the eye, where sight-threatening disease often occurs. The Company’s unique platform is inherently flexible and intended to work with established and new formulations of medications. Clearside’s patented SCS Microinjector^® can deliver a wide variety of drug candidates into the suprachoroidal space, providing targeted delivery to potentially improve efficacy and compartmentalization of medication to reduce or eliminate toxic effects on non-diseased cells. The SCS Microinjector is comprised of a syringe with a custom-designed hub and two 30-gauge hollow microneedles of varying lengths, each approximately one millimeter, optimizing insertion and suprachoroidal administration of drugs.

About Clearside Biomedical, Inc.

Clearside Biomedical, Inc. is a biopharmaceutical company revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space (SCS^®) to improve patient outcomes. Clearside’s SCS injection platform, utilizing the Company’s patented SCS Microinjector^®, enables an in-office, repeatable, non-surgical procedure for the targeted and compartmentalized delivery of a wide variety of therapies to the macula, retina, or choroid to potentially preserve and improve vision in patients with sight-threatening eye diseases. Clearside is developing its own pipeline of small molecule product candidates for administration via its SCS Microinjector. The Company’s lead program, CLS-AX (axitinib injectable suspension), is in development for the treatment of neovascular age-related macular degeneration (wet AMD). Planning for a Phase 3 program is underway. In addition, Clearside is evaluating various small molecules for the potential long-acting treatment of geographic atrophy (GA). Clearside developed and gained approval for its first product, XIPERE^® (triamcinolone acetonide injectable suspension) for suprachoroidal use, which is available in the U.S. through a commercial partner. Clearside also strategically partners its SCS injection platform with companies utilizing other ophthalmic therapeutic innovations. For more information, please visit clearsidebio.com or follow us on LinkedIn and X.

Cautionary Note Regarding Forward-Looking Statements

Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “believe”, “expect”, “may”, “plan”, “potential”, “will”, and similar expressions, and are based on Clearside’s current beliefs and expectations. These forward-looking statements include statements regarding the clinical development of CLS-AX, including the planned Phase 3 trial design, CLS-AX’s potential impact on the wet AMD market, as well as the potential benefits of CLS-AX, Clearside’s suprachoroidal delivery technology and Clearside’s SCS Microinjector^®. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the conduct of clinical trials, Clearside’s reliance on third parties over which it may not always have full control, Clearside's ability to raise additional capital, and other risks and uncertainties that are described in Clearside’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission (SEC) on March 12, 2024, Clearside’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed with the SEC on November 12, 2024, and Clearside’s other periodic reports filed with the SEC. Any forward-looking statements speak only as of the date of this press release and are based on information available to Clearside as of the date of this release, and Clearside assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise.

Investor and Media Contacts:

Jenny Kobin
Remy Bernarda
ir@clearsidebio.com

Source: Clearside Biomedical, Inc.

FAQ

What are the key features of Clearside's CLS-AX Phase 3 trials for wet AMD?

The trials will include two concurrent non-inferiority studies with 450 treatment-naïve participants each, comparing CLS-AX (1 mg) to aflibercept (2 mg), with primary endpoint measuring BCVA change at Week 52.

How does the dosing schedule for CLSD's CLS-AX differ from existing wet AMD treatments?

CLS-AX offers flexible maintenance dosing every 3 to 6 months based on patient disease assessments, potentially providing longer intervals between treatments compared to current options.

What is the market potential for Clearside's CLS-AX in wet AMD treatment?

CLS-AX targets the $12+ billion wet AMD market, offering potential advantages through its flexible dosing, extended duration, and suprachoroidal delivery method.

What are the primary endpoints for CLSD's Phase 3 CLS-AX trials?

The primary endpoint is the average change in best corrected visual acuity (BCVA) from baseline at Week 52, ensuring participants receive multiple doses of CLS-AX.

How will patient selection be optimized in Clearside's Phase 3 CLS-AX trials?

The trials will use tight screening criteria, eliminate participants with highly variable visual acuity, and focus on treatment-naïve patients to reduce variability and enable faster recruitment.