Clearside Biomedical offers progress report in ODYSSEY Phase 2b trial of CLS-AX in wet AMD

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Clearside Biomedical Inc revealed that it has completed randomization in its ODYSSEY Phase 2b clinical trial (NCT05891548) of CLS-AX (axitinib injectable suspension) in neovascular age-related macular degeneration (wet AMD).

The company noted in a news release that topline data results are expected in the third quarter of 2024.¹

“As we continue to make significant progress in our ODYSSEY trial, we are optimistic about the potential benefits of CLS-AX, our proprietary suspension of axitinib for suprachoroidal injection,” George Lasezkay, PharmD, JD, president and CEO, said in a news release. “Axitinib is a highly-potent tyrosine kinase inhibitor (TKI) that achieves pan-VEGF blockade, directly inhibiting VEGF receptors-1, -2, and -3 with high potency and specificity. We believe TKIs have the potential to play a significant role in the treatment of wet AMD.”

Laskey added the company has specific goals with its ODYSSEY trial.

“In ODYSSEY, we are looking to replicate the excellent safety profile, stable vision, and reduced frequency of injections we observed in our OASIS Phase 1/2a trial and its 3-month Extension Study,” he concluded in the news release. “The differentiated mechanism of action and high potency of axitinib combined with delivery into the suprachoroidal space with our proprietary SCS Microinjector has the potential to be a best-in-class approach for long-term maintenance therapy for wet AMD patients.”

ODYSSEY Phase 2b clinical trial

According to the company, ODYSSEY is a randomly assigned, double-masked, parallel-group, active-controlled, multi-center, 36-week Phase 2b clinical trial in participants with wet AMD. The study is designed to evaluate at least 60 participants randomized to either CLS-AX (1 mg) or aflibercept (2 mg) with a 2:1 randomization schedule (40 participants in CLS-AX arm and 20 participants in aflibercept arm). CLS-AX is administered by suprachoroidal injection via Clearside’s SCS Microinjector, and aflibercept is administered via intravitreal injection.¹

Moreover, the company noted that eligible participants were treatment-experienced and underwent diagnostic imaging at their screening visit followed by masked reading center confirmation of persistent active disease. Furthermore, the primary outcome measure is the mean change from baseline in best corrected visual acuity, while the secondary outcome measures include other changes from baseline in visual function and ocular anatomy, the need for supplemental treatment, and treatment burden as measured by total injections over trial duration. The trial is designed to provide the necessary parameters to design a Phase 3 program.

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.¹

According to the company, 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 preclinical studies in multiple species and in a Phase 1/2a wet AMD clinical trial in which CLS-AX was well tolerated and demonstrated an excellent 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 and thereby limiting drug exposure to the front of the eye. Clearside is developing CLS-AX as a long-acting therapy for the treatment of retinal diseases.

Age-related macular degeneration causes a progressive loss of central vision and is the most common cause of legal blindness in individuals over age 55. Neovascular AMD (Wet AMD) is generally caused by abnormal blood vessels that leak fluid or blood into the macula, the part of the retina responsible for central vision, and accounts for the majority of vision loss in patients with this disorder. In the US, approximately 11 million patients are living with AMD,² and about 10% have the wet form.³

According to the company, the current course of treatment requires life-long, frequent injections to maintain efficacy. This treatment regimen tends to cause a treatment burden for patients resulting in reduced compliance and under-treatment leading to potentially limited outcomes. In the US, the total economic impact of late-stage AMD is estimated to be approximately $49 billion, with the majority of costs attributed to lower productivity related to job loss or job reduction due to the condition.⁴

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®). 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), for the treatment of neovascular age-related macular degeneration (wet AMD), is in Phase 2b clinical testing. 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.

References

1. Clearside Biomedical Reports Significant Progress in ODYSSEY Phase 2b Trial of CLS-AX in Wet AMD | Clearside Biomedical, Inc.- IR Site. Clearside Biomedical, Inc.- IR Site. Published December 14, 2023. Accessed December 14, 2023. https://ir.clearsidebio.com/news-releases/news-release-details/clearside-biomedical-reports-significant-progress-odyssey-phase

2. Pennington, Katie L and DeAngelis, Margaret M, Eye and Vision, Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors, Dec 22, 2016.

3. Prall, F Ryan and Ciulla, Thomas A, Medscape: Exudative (Wet) Age-Related Macular Degeneration (AMD), June 16, 2022.

4. Retina International, The Socio-economic Impact of Age-related Macular Degeneration (AMD) in Bulgaria, Germany, and USA, Oct 12, 2022.