Clearside Biomedical unveils positive topline results from ODYSSEY Phase 2b Trial of suprachoroidal CLS-AX in wet AMD

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Clearside Biomedical Inc announced the ODYSSEY Phase 2b clinical trial of CLS-AX (axitinib injectable suspension) for the treatment of neovascular age-related macular degeneration (wet AMD) achieved both its primary and secondary outcomes.

CLS-AX 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.

Moreover, the suprachoroidal injection axitinib has demonstrated meaningful potential in preclinical studies in multiple species, and in both 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.¹

According to the company, in participants who received CLS-AX delivered suprachoroidally, best corrected visual acuity (BCVA) and ocular anatomy (central subfield thickness) were stable up to 6 months compared to participants who received aflibercept. In addition, CLS-AX demonstrated a well-tolerated safety profile to Week 36 inclusive of mandatory re-dosing of CLS-AX at Week 24.

George Lasezkay, PharmD, JD, president and CEO of Clearside Biomedical, said the company was pleased to report positive topline data from its successful ODYSSEY Phase 2b trial.”

“These encouraging results strongly support advancing our CLS-AX wet AMD program into Phase 3 development and provide further evidence of the potential benefits of delivering medicines to the back of the eye using our proprietary SCS Microinjector,” he said. “We achieved our primary outcome of maintaining stable BCVA throughout the trial as measured by the mean change in BCVA from baseline to Week 36. CLS-AX consistently reduced the frequency of injections after the initial dose of CLS-AX with approximately 90% of CLS-AX participants not requiring any additional treatment up to 4 months, 81% not requiring any additional treatment up to 5 months, and 67% not requiring any additional treatment up to 6 months before mandatory re-dosing at Week 24.”

Lasezkay said the company believes the data supports its goal to potentially provide a safe, convenient wet AMD treatment option with the advantage of a flexible maintenance dosing regimen between 3 to 6 months.

“We look forward to continuing to analyze the results and share additional data analysis with the retina community at upcoming medical meetings,” he said.

Victor Chong, MD. MBA, chief medical officer of Clearside, noted that CLS-AX demonstrated extended duration and stable vision and anatomic measures throughout the trial in a difficult-to-treat patient population with reading center confirmed active disease early in their treatment journey.

“ODYSSEY confirmed the ability to administer multiple doses of CLS-AX from 12 weeks up to 36 weeks with a well-tolerated safety profile,” Chong said. “We believe the ability to deliver multiple doses as needed between 12 and 36 weeks is a key differentiator from other treatments in development. In the trial, we observed that CLS-AX, delivered into the suprachoroidal space using our SCS Microinjector can be flexibly dosed similar to current biologic treatments, but has the potential to last longer because it is a highly potent tyrosine kinase inhibitor that achieves pan-VEGF blockade.”

Chong said the company’s goal is to provide a new and important treatment option with meaningful efficacy, safety, and delivery benefits for patients and retina specialists.

“These topline results provide valuable data in wet AMD with repeat dosing data to better inform and potentially de-risk our planned Phase 3 program design,” Chong added.

David M. Brown, MD, director of research, Retina Consultants Houston, noted that the results were encouraging.

“These data are encouraging and demonstrate that suprachoroidal CLS-AX may have sustained durability beyond our currently approved agents,” he said. “The positive safety profile, potential flexible dosing and patient acceptance of CLS-AX being delivered directly to the back of the eye via Clearside SCS microinjector has the potential to improve the treatment landscape for patients and physicians looking for a long-acting treatment for wet AMD.”

ODYSSEY topline data

According to the company, ODYSSEY was a randomly assigned, double-masked, parallel-group, active-controlled, multicenter, 36-week, Phase 2b clinical trial in participants with wet AMD previously treated with intravitreal anti-vascular endothelial growth factor (VEGF) standard of care therapy. A total of 60 participants were treated for 36 weeks and 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).

The company noted that CLS-AX was administered by suprachoroidal injection via Clearside’s SCS Microinjector, and aflibercept was administered through an intravitreal injection. Participants in the trial were determined to have active disease with a median duration of wet AMD diagnosis of 9.9 months. Eligible participants underwent diagnostic imaging at their screening visit, followed by masked reading center confirmation of persistent active disease.

Primary and secondary outcomes

The ODYSSEY trial achieved its primary and secondary outcomes including the mean change from baseline in BCVA, changes from baseline in visual function and ocular anatomy, the need for supplemental treatment, treatment burden as measured by total injections over the trial duration, and safety measures.

CLS-AX efficacy results

• Maintained stable BCVA throughout the trial as measured by the mean change in BCVA from baseline to Week 36.
• Maintained stable central subfield retinal thickness (CSRT) throughout the trial as measured by the mean change in CSRT from baseline to Week 36 as confirmed by the independent reading center.

CLS-AX durability results

• CLS-AX participants not requiring any additional treatment:
  • 100% up to 12 weeks (3 months); n=40/40
  • 90% up to 16 weeks (4 months); n=36/39
  • 81% up to 20 weeks (5 months); n=30/37
  • 67% up to 24 weeks (6 months) before mandatory re-dosing at Week 24; n=26/39
• Reduced injection frequency by approximately 84% compared to the average monthly injections in the 24 weeks prior to screening

CLS-AX safety and tolerability results

• Well-tolerated safety profile through 36 weeks that included mandatory re-dosing of CLS-AX at Week 24
• No ocular serious adverse events (SAEs) or treatment-related SAEs
  • No drug or procedure-related ocular SAEs
  • No reported drug or procedure-related systemic SAEs
  • No endophthalmitis
  • No retinal vasculitis
• Positive adverse event profile

Similar discontinuation rates between treatment and comparator groups.

Reference:

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