Clearside Biomedical, Inc. announced two major updates for the clinical development of its suprachoroidal space (SCS) therapy for wet age-related macular degeneration (AMD): CLS-AX (axitinib injectable suspension).
First, a rundown on this SCS therapy.
CLS-AX is a proprietary suspension of axitinib intended for suprachoroidal injection as a longer-acting therapy for retinal disease detachment (wet AMD).
- About axitinib: A highly potent tyrosine kinase inhibitor (TKI), this is already approved as an oral tablet formulation to treat advanced renal cell carcinoma.
The goal of CLS-AX: To block three vascular endothelial growth factor (VEGF) receptors—with a high specificity—and achieve “pan-VEGF inhibition.”
And in the context of wet AMD?
Through this VEGF blockade, Clearside identified potential “efficacy advantages” over current retinal therapies on the market.
How, exactly? By “acting at a different level of the angiogenesis cascade” as well as possibly benefiting patients with a suboptimal response to anti-VEGF therapies, according to the company.
- See here for three distinct efficacy advantages
Now to the important component: the TKI delivery.
This brings us to Clearside’s SCS Microinjector, a proprietary and not yet-approved patent-protected technology injection platform designed as a microneedle device.
What it does: Provides a targeted delivery of drugs (such as CLS-AX and the FDA-approved XIPERE [triamcinolone acetonide injectable suspension]) into the SCS to reduce or eliminate potential toxic effects.
In terms of timing: This is intended to enable a more flexible dosing schedule for long-term maintenance.
Let’s talk about these updates.
We’ll start with the first: Feedback from the company’s end-of-phase 2 meeting with the FDA.
Clearside President and CEO George Lasezkay, PharmD, JD, noted that the company had a “positive outcome” after receiving the formal meeting minutes from the federal agency.
Specifically, the meeting and formal minutes were reported to confirm key components to Clearside’s plans for two proposed phase 3 trials as well as an agreement on the protocol design, patient population, primary and secondary endpoints, and the use of sham injections.
Go on …
Chief Medical Officer Victor Chong, MD, MBA, emphasized the company’s positive and productive interactions with the FDA, stating that they are both “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,” stated Dr. Chong, who also serves as executive vice president, head of Research and Development.
So what will this phase 3 program look like?
The company offered a highlights version of what to expect from both concurrent, noninferiority, pivotal trials.
- The participants: Treatment naïve patients (representing the general wet AMD population)
- The setup: Two arms per trial with ~225 patients per arm comparing:
- CLS-AX (1 mg)
- Aflibercept (2 mg)
- The primary endpoint: Average change in best-corrected visual acuity (BCVA) from baseline at Week 52 (to guarantee patients receive multiple CLS-AX doses)
Other agreed-upon aspects of the program include:
- Optimization of study population to reduce variability
- Utilizing tight screening criteria
- Eliminating participants with highly variable visual acuity (VA) before randomization
- Detailed redosing criteria used for CLS-AX (to reduce need for rescue treatment)
- 1-year safety follow-up period that meets registration requirement to submit 2 years’ worth of safety data
So when can we expect this program to kick off?
No concrete date has been announced as of yet … so stay tuned.
And keep in mind: The plan behind this program is that, by targeting the more general wet AMD population, there may be an even greater percentage of participants who can reach 6 months without the need for other intervention.
Got it. In the meantime, how has CLS-AX clinically performed thus far?
It’s promising, to say the least.
As we reported in October 2024, the phase 2b Odyssey trial (NCT05891548) met both its primary and secondary endpoints, with CLS-AX demonstrating a “well-tolerated” safety profile.
The data: Injection frequency among CLS-AX-treated patients was reduced by 84%, with
- 100% not requiring any additional treatment up to 12 weeks
- 67% not requiring any additional treatment up to 24 weeks
And more recently (as in, last month): The company released analyses of two participant subgroups from that phase 2b trial that provided key clinical insights into the upcoming phase 3 program design.