Clearside Biomedical, Inc. announced new topline data from its phase 2b ODYSSEY trial evaluating CLS-AX (axitinib injectable suspension) for the treatment of wet age-related macular degeneration (AMD).
Let’s start with this candidate.
CLS-AX is a highly potent tyrosine kinase inhibitor (TKI) that originated as an oral tablet formulation widely used for the treatment of advanced renal cell carcinoma.
- To note: TKIs generally block chemical messengers (enzymes) known as tyrosine kinases (which help to send growth signals in cells). By blocking these, cell growth and division is prevented.
How CLS-AX works: By targeting vascular endothelial growth factor (VEGF) and directly blocking VEGF receptors-1, -2, and -3—with high specificity—resulting in pan-VEGF inhibition.
And the benefit of this for wet AMD?
Per the company, this “broad VEGF blockade” is believed to have efficacy advantages over existing retinal therapies, with the potential to benefit patients who don’t respond adequately to more narrowly focused anti-VEGF therapies.
Gotcha. And how is this therapy delivered?
For wet AMD, CLS-AX is delivered via Clearside’s patented suprachoroidal space (SCS) Microinjector.
About the SCS Microinjector: This patent-protected, proprietary SCS injection platform provides access to the back of the eye and delivers drugs into the SCS—enabling targeted delivery and reducing/eliminating potential toxic effects.
- The platform features a syringe, a custom-designed hub, and two 30-gauge hollow microneedles for suprachoroidal administration.
- To note: This treatment approach is the first (and currently only) FDA-approved method for accessing the SCS.
- See a visual of this (and real-world patient experiences here).
- To note: This treatment approach is the first (and currently only) FDA-approved method for accessing the SCS.
Alrighty, now talk about this study.
The ODYSSEY study was designed as a randomized, double-masked, parallel-group, active-controlled, multicenter phase 2b trial (NCT05891548) that enrolled 60 patients diagnosed with wet AMD and randomized 2:1 between the CLS-AX and aflibercept arms.
About these patients: Participants were determined based on their active disease (wet AMD), with a mean duration of diagnosis of 9.9 months.
And the setup?
- Group 1 (n = 40): CLS-AX 10 mg/mL (1.0 mg in 0.1 mL) administered via suprachoroidal injection on Day 1 (loading dose) and then every 12 to 24 weeks
- CLS-AX was dosed at least every 24 weeks unless disease activity assessment indicated the need for supplemental treatment.
- Subsequently, CLS-AX was administered 12 weeks after the last dose; however, if less than 12 weeks, aflibercept may be given.
- Group 2 (n = 20): Aflibercept (2 mg in 0.05 mL) administered via intravitreal injection on a fixed-dose regimen once every 8 weeks (Q8W)
The study duration: 36 weeks.
And what was measured?
The primary outcome: mean change in best-corrected visual acuity (BCVA) from baseline to Week 36.
Secondary outcomes included:
- 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
Now to these findings.
First off: The study met both primary and secondary outcomes, the company reported.
- Specifically: CLS-AX-treated patients were stable (versus aflibercept-treated patients) for up to 6 months for the following:
- BCVA
- Ocular anatomy (central retinal subfield thickness [CRST])
How was CLS-AX’s safety profile?
It demonstrated a “well-tolerated safety profile,” according to Clearside, “to Week 36 inclusive of mandatory re-dosing at Week 24.”
And its durability among patients?
This is where we get into the numbers.
For the 40 CLS-AX-treated participants, the following percentages did not require any additional treatment:
- 100% up to 12 weeks (3 months)
- n=40/40
- 90% up to 16 weeks (4 months)
- n=35/39
- 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
The company also noted that injection frequency was reduced by an estimated 84% when compared to patients’ average monthly injections in the 24 weeks prior to the study screening.
Did any adverse events develop?
A “positive adverse event” (AE) profile was reported, with no occurrences of ocular serious AEs (SAEs) nor treatment-related SAEs.
That extended to:
- No drug or procedure-related ocular SAEs
- No reported drug or procedure-related systemic SAEs
- No endophthalmitis
- No retinal vasculitis
What’s significant about this data?
We’ll start with CLS-AX’s mechanism of action: “We believe the ability to deliver multiple doses as needed between 12 and 36 weeks is a key differentiator from other treatments in development,” stated Victor Chong, MD, MBA, Clearside’s chief medical officer.
Also important: CLS-AX’s prolonged duration and targeted delivery to the affected tissues—all while minimizing drug exposure to the front of the eye.
And how does the phase 2 findings compare to prior clinical data?
On par with previously reported positive data from the OASIS phase 1/2a study.
Those findings were reported in November 2022 (along with positive 6-month data from an extension trial in February 2022).
Click here and here for those details.
Nice! So what’s the plan moving forward?
The company is planning to use this positive data to better inform the design of a phase 3 program on CLS-AX for wet AMD. Stay tuned for details on that!