A novel sustained-release axitinib implant has demonstrated promising efficacy and safety in treating non-proliferative diabetic retinopathy (NPDR), potentially addressing a significant treatment gap for patients with this progressive eye condition.
Interim 48-week results from the Phase 1 HELIOS trial, presented at the 2024 American Society of Retina Specialists (ASRS) meeting in Stockholm, Sweden, showed that OTX-TKI was well-tolerated and effective in preventing disease progression in patients with moderately severe to severe NPDR.
Addressing an Unmet Clinical Need
Despite substantial evidence supporting anti-VEGF therapy for NPDR, less than 1% of patients currently receive such treatment, with approximately two-thirds of retina specialists not recommending intervention for NPDR patients without diabetic macular edema (DME).
"Diabetic retinopathy is a chronic, progressive, burdensome disease, and we know that there's a large body of level 1 data that shows that treating with anti-VEGF, in a regular fashion, can reduce progression of DRSS and also reduce vision-threatening complications," explained Dr. Dilsher Dhoot of California Retina Consultants, the study's presenting investigator.
The reluctance to treat earlier stages of diabetic retinopathy stems largely from the high treatment burden associated with frequent intravitreal injections. OTX-TKI aims to overcome this barrier by providing a durable treatment option requiring significantly fewer injections.
Innovative Drug Delivery Technology
OTX-TKI combines Ocular Therapeutix's proprietary Elutex technology—a bioresorbable polymer matrix—with axitinib, a tyrosine kinase inhibitor (TKI) with high affinity for VEGF receptor 2. The implant is administered via a single 25-gauge intravitreal injection and is designed to bioresorb over 6-12 months while maintaining biological effectiveness throughout this period.
Trial Design and Patient Population
The HELIOS trial enrolled 21 evaluable participants across 10 U.S. centers, randomized in a 2:1 ratio to receive either a single 0.6 mg OTX-TKI injection or a sham procedure. Eligible patients had moderately severe to severe NPDR (DRSS levels 47-53) and baseline visual acuity of ≥69 ETDRS letters.
Participants could not have received anti-VEGF treatment or dexamethasone intravitreal implant in the previous 12 months, or intraocular steroid injections within the prior 4 months.
Compelling Efficacy Results
At the 48-week mark, the OTX-TKI group showed significant improvements in diabetic retinopathy severity:
- 23.1% of treated patients achieved a ≥2-step improvement in DRSS
- 46.2% experienced a 1- or 2-step improvement
- No patients in the OTX-TKI group showed disease worsening
In stark contrast, the sham control group showed:
- 0% improvement in DRSS
- 25% of patients experienced disease worsening
- 37.5% developed vision-threatening complications, including center-involved DME or proliferative diabetic retinopathy
"We saw that there was 37.5% vision-threatening complications in the sham group at week 48, compared to 0% in the OTX-TKI arm," Dr. Dhoot highlighted.
The drug also demonstrated biological activity in patients with non-center-involving DME, with all such patients in the treatment arm showing improvement by week 48.
Favorable Safety Profile
OTX-TKI was generally well-tolerated with no reports of ocular serious adverse events. Importantly, there were no instances of intraocular inflammation, iritis, vitritis, or vasculitis—concerns that can arise with intravitreal therapies.
This safety profile aligns with previous Phase 1 trials of OTX-TKI in neovascular age-related macular degeneration, providing additional confidence in the drug's tolerability.
Future Implications for Clinical Practice
The durability of OTX-TKI's effect is particularly noteworthy, potentially allowing patients to maintain stable disease with just one or two injections per year—a dramatic reduction in treatment burden compared to current anti-VEGF regimens.
"I think the data presented today is compelling, and look forward to larger trials looking at OTX-TKI, which could potentially be a durable, 1–2 injection per year treatment for patients with moderately severe and severe NPDR to help prevent complications in a proactive fashion," Dr. Dhoot stated.
While the sample size was limited (13 patients in the treatment arm and 7-8 in the control group), these promising results suggest OTX-TKI could fundamentally change the treatment paradigm for NPDR by enabling earlier intervention with manageable treatment burden.
The sponsor is reportedly planning to advance OTX-TKI into the next phase of clinical development based on these encouraging results, potentially bringing this innovative therapy closer to clinical availability for the millions of patients living with diabetic retinopathy.
