Clearside Biomedical, Inc. has opened patient enrollment in its phase 2b ODYSSEY trial on CLS-AX (axitinib injectable suspension) for suprachoroidal delivery in neovascular age-related macular degeneration (wet AMD).
Tell me more about CLS-AX.
CLS-AX (axitinib injectable suspension) is a tyrosine kinase inhibitor (TKI) that originated as an oral tablet formulation widely used for the treatment of advanced renal cell carcinoma.
It works by targeting vascular endothelial growth factor (VEGF) and directly blocking VEGF receptors-1, -2, and -3.
In wet AMD, CLS-AX is being delivered via Clearside’s patented suprachoroidal space (SCS) Microinjector.
What is this SCS Microinjector?
The company’s patent-protected, proprietary suprachoroidal space (SCS) injection platform includes a syringe, custom-designed hub, and two 30-gauge hollow microneedles for suprachoroidal administration.
The treatment approach provides access to the back of the eye and delivers drugs into the suprachoroidal space (enabling targeted delivery and reducing / eliminating potential toxic effects).
How has it performed so far?
In November 2022, positive data from the phase 1/2a OASIS clinical trial reported CLS-AX to be well-tolerated and demonstrated a favorable safety profile.
Positive data was also released in February 2023 from a 6-month extension trial.
Now let’s talk about this new trial.
The randomized, double-masked, parallel-group, active-controlled, multicenter phase 2b ODYSSEY trial is enrolling 60 patients diagnosed with wet AMD and randomized 2:1 between CLS-AX and aflibercept arms.
See here for a brief rundown on patient criteria.
And the doses?
Two-thirds (40) of patients will receive CLS-AX and 20 patients will be administered aflibercept.
Participants in both arms will receive three monthly 2 mg loading doses of aflibercept while participants in the CLS-AX arm will be administered one loading dose of 1.0 mg CLS-AX at the same visit as the baseline dose of aflibercept.
And then?
After that, patients will receive (in the CLS-AX arm) CLS-AX at least every 24 weeks, unless disease activity assessment indicates the need for supplemental treatment.
Subsequently, CLS-AX might be administered 12 weeks after the last dose; however, if less than 12 weeks, aflibercept may be given.
For patients in the aflibercept arm, they will be administered aflibercept on a fixed-dosing regimen every 8 weeks.
What’s being measured?
The primary outcome includes a mean change in best-corrected visual acuity (BCVA) from baseline to Week 36.
Secondary outcomes are the following:
- Other changes in visual function and ocular anatomy
- Need for supplemental treatment (see here for the criteria; based on measurement changes due to wet AMD)
- Treatment burden, measured by total injections through Week 36.
What else?
Per CEO George Lasezkay, PharmD, JD, the company intends to use the criteria and outcome measures of the ODYSSEY trial to design a potential phase 3 program for CLS-AX.
So now what?
Investigators are targeting 30 U.S.-based clinical trial sites for enrollment; the company plans to release topline data by Q3 2024.
Overall significance?
According to Clearside, its suprachoroidal injectable suspension of CLS-AX has the potential for prolonged duration and target delivery to the affected tissue layers (while minimizing drug exposure to the front of the eye) in wet AMD.