Ocular Therapeutix, Inc. provided an update regarding three key clinical trials evaluating the use of its lead asset AXPAXLI (axitinib intravitreal implant) for the treatment of wet age-related macular degeneration (AMD) and nonproliferative diabetic retinopathy (NPDR).
Let’s start with this investigational candidate.
AXPAXLI (also known as OTX-TKI) is an investigational, bioresorbable hydrogel intravitreal implant with anti-angiogenic properties.
Its proposed purpose: The intravitreal implant is being designed to continuously deliver axitinib (a small-molecule, multi-target tyrosine kinase inhibitor [TKI]) for the following indications:
- Diabetic retinopathy (DR)
- Vascular endothelial growth factor (VEGF-mediated retinal diseases:
- Wet AMD
And how is axitinib delivered?
Via a 25G needle and the company’s proprietary ELUTYX technology platform, which is a bioresorbable polymer matrix hydrogel developed to provide localized, sustained-release drug delivery.
- The duration: A 9 to 12-month target release
And the goal: To facilitate targeted drug delivery and minimize systemic exposure (per the company).
Gotcha. Now let’s talk about this wet AMD update.
The company reported that 151 participants have been enrolled across 60 clinical study sites in the SOL-1 phase 3 study for wet AMD so far.
- The study: A multicenter, double-masked, randomized (1:1), parallel group trial (NCT06223958)
- Target participants: 300 (estimated) treatment-naïve wet AMD patients (aged 50+)
- The design: 8-week loading stage, 9-month treatment stage, and safety follow-up
- Loading stage: Participants (20/80 vision or better) receive 2 mg aflibercept at Week -8 and -4
- Treatment stage: Participants randomized to receive a single AXPAXLI dose or aflibercept (and then assessed monthly for the study duration) if they:
- Achieve visual acuity (VA) of 20/20, or
- Gain at least 10 Early Treatment Diabetic Retinopathy (ETDRS) letters at Day 1
What’s being measured?
Primary outcome is best-corrected visual acuity (BCVA), measured by maintaining VA ( <15 ETDRS) at Day 1 (up to 36 weeks).
The other outcome measure: Development and severity of treatment-emergent adverse events (TEAEs), measured up to 104 weeks.
And when can we expect topline data?
According to Clinical Trials, the study is slated to conclude in September 2027 … but definitely stay tuned for interim data to be released before then.
Alrighty then … any other updates for wet AMD?
Yes, actually. Ocular Therapeutix reported its plans to initiate the phase 3 SOL-R repeat dosing study on AXPAXLI, in which the the following will be evaluated:
- AXPAXLI (450µg) dosed at 6 months (Q6M)
- Aflibercept (2 mg) doseD every 8 weeks (Q8W)
- Comparator arm Q6M
The participants: 825 wet AMD patients.
Is there a specific protocol for this?
Here’s what we know: Participants will include (initially, at least) those who failed loading/randomization in the SOL-1 study.
So the protocol: All participants enrolled must receive “multiple aflibercept (2 mg) loading doses and monitored to ensure limited retinal fluid fluctuations prior to randomization.”
- Then: After enrollment completion and randomization of the SOL-1 study, those participants will be directly enrolled in the SOL-R study.
- Note: The company has also requested a Type C meeting with the FDA regarding the study’s protocol (we’ll keep you posted on that outcome).
What’s next?
Clinical data: Specifically, on the 48-week data from the phase 1 HELIOS study evaluating AXPAXLI for NPDR (which builds on 40-week data the company reported in April 2024).
- The study: multicenter, double-masked, randomized (2:1), parallel group phase 1 STUDY (NCT05695417)
- Target participants: 21 (estimated) patients (aged 21+) diagnosed with NPDR
- The design:
- Single AXPAXLI (600 µg)
- Single sham injection
- Note: no loading treatment for either arm
Now this data.
A total of 23% (n = 3) of participants demonstrated a ≥2-step Diabetic Retinopathy Severity Scale (DRSS) improvement in the AXPAXLI arm at week 48 vs 0% in the sham arm.
Plus: An additional 23.1% of patients (n = 3) demonstrated a 1-step DRSS improvement in the AXPAXLI arm vs 0% in the sham arm.
Go on …
Interestingly enough, 0% of AXPAXLI-treated patients demonstrated DRSS worsening by Week 48m while 25% of sham-treated patients did.
Even further: None of AXPAXLI-treated patients developed PDR or center-involved diabetic macular edema (CI-DME) at Week 48 vs 37% of sham-treated patients.
And on average?
AXPAXLI-treated patients demonstrated improvements in central subfield thickness (CST) compared to sham-treated patients—who actually worsened by the 48-week follow up.
Which leads to, overall: AXPAXLI was found to be well-tolerated, with no resulting reports of intraocular inflammation, iritis, vitritis, or vasculitis, the company reported.
Quite a lot of updates!
Indeed! And this all follows Ocular Therapeutix’s announcement earlier this month of its intention to cut 13% of its full-time employee workforce.
The reasoning: It’s all part of the company’s initiative to prioritize resources for the clinical development of AXPAXLI.
Read our coverage here.