PolyActiva has released new findings from its phase 1b/2a clinical trial (LATA-CS102) evaluating the use of PA5108, its novel glaucoma treatment technology, in providing long-term drug delivery for glaucoma patients.
Give me the rundown on PolyActiva.
Headquartered in Melbourne, Australia, the clinical-stage ophthalmology company has developed a proprietary polymeric prodrug technology (more on that in a moment) on which its portfolio of investigational, next-generation ocular implants is based.
Two implants are currently under clinical development to provide a “safe and effective, fully biodegradable therapy” for a wider range of ocular diseases.
These include:
- Latanoprost FA SR ocular implant (our topic of choice)
- Proposed indication: To reduce intraocular pressure (IOP) caused by open-angle glaucoma (OAG) and ocular hypertension (OHT)
- Levofloxacin ocular implant
- Proposed indication: To reduce endophthalmitis risk following cataract surgery
And the intent for these implants?
Ideally, the company is looking to reduce patients’ reliance on daily eye drops in the long term—an all-too-common “mainstay” associated with glaucoma management.
Circle back to this tech.
Dubbed “Prezia,” this proprietary tech works by chemically attaching a drug to a carrier polymer, which is designed to provide five key clinically beneficial features:
- Precision
- Delivering a constant daily dose of drug tailed to each application
- Control
- Delivering therapy for varying durations (one week or 12 months) with no “burst effect or loss of efficacy”
- Versatility
- For any drug produced chemically, it enables single or multiple drug combinations specifically tailored to a clinical indication
- Repeatability
- Consistently rapid biodegradation that allows for repeated implant administration
- Adaptability
- Capability for its geometric form to be a rod-shaped implant, injectable gel, or topical film
Can I get a visual of the process?
You bet.
https://youtu.be/lzm1tVzDgjc
Now some background on this glaucoma implant.
As PolyActiva’s lead candidate, latanoprost free-acid (FA) sustained-release (SR) ocular implant (PA5108) is designed to provide a constant daily therapeutic dose of latanoprost FA.
How it’s administrated: Via a rapid and minimally-invasive in-office procedure intended to be integrated into the clinical workflow and aligned with a patient’s regular visit schedule.
- And the effect of these doses: Ideally, IOP reduction over a 6-month period
Bringing in the “biodegradable” component: PolyActiva noted that the implant rapidly degrades once the drug is released (not persisting beyond 4 to 6 weeks following treatment), enabling repeat dosing.
Nice! Next: This study.
The multi-center, open-label, interventional, comparative, dose-ranging trial (NCT04060758) is looking to identify a single dosage of PA5108 that is both safe and efficacious within a specific range.
- Participants: OAG patients (aged 18+; see criteria)
- Prior to receiving their respective implant and dose, patients were required to wash out of their IOP-lowering medications.
- The setup: A single ascending-dose design with three single-dose cohorts of the following implant strengths:
- Low-dose cohort: 14.7 mcg (n =10)
- Mid-dose cohort: 26.6 mcg (n =10)
- Repeat-dose cohort: 14.7 mcg (n=17)
- Patients received their first implant on Day 0 and their second within seven days of the study’s Week 21 assessment
- The goal: To identify the minimum effective dose that provides a ≥20% IOP lowering effect at 12 weeks with minimal adverse events (AEs)
- Time frame:
- IOP measured at baseline, Week 12, and Week 26
- Treatment-emergent AEs measured throughout study duration up to 1 year
- Time frame:
To note: Investigators chose not to recruit a high-dose cohort after they reached efficacy targets with the low- and mid-dose implants.
Alrighty, now to these findings.
First thing to know is the number of participants included in this latest phase 2 data (n = 17) and that this data is as of the study’s 48-week mark.
Specifically: PolyActiva reported that these 17 patients received two PA5109 implants, 21 weeks apart—and of that number, 15 have now reached the 48-week mark of the study.
Based on this, the company stated that the study met both its efficacy and safety endpoints.
Details, please.
Statistically significant IOP changes were observed (from baseline) for each of the study’s mean diurnal measurements at Weeks 12, 21, 33, and 42 (p<0.001), according to PolyActiva.
Further: IOP reductions were noted as “clinically meaningful” at 8 a.m. over 48 weeks (between 26% and 35%).
Also by the 48-week treatment point: 94% of participants had no need for additional drop therapy.
And the implant’s safety performance?
As of the 48-week point, PA5108 was found to be “safe and generally well tolerated” among participants, with “no adverse impact” on the corneal endothelium after repeat dosing.
This definitely sounds promising … but how does it compare to prior data?
Reported in November 2023, interim phase 2a data from this same study was based on findings at the 26-week mark, after which the implant biodegraded.
In that case, PAG5108 demonstrated a >20% reduction in IOP at the 12- and 26-week mark.
Additionally, the company previously reported that the implant’s “rapid biodegradation profile” had enabled eight patients to receive a second implant at Week 21—”providing ongoing, uninterrupted therapy, with no product-related (AEs).”
This all sounds promising! So what’s next?
PolyActiva stated it is currently “scaling up its manufacturing capabilities” to support its upcoming initiation of a late-stage trial on PA5108 in early 2025.
Most importantly: The company plans to conduct trials “under an (investigational new drug) submission to the FDA.”