Ocular Therapeutix, Inc. announced 12-month data from the phase 1 U.S.-based clinical trial assessing OTX-TKI for the treatment of wet age-related macular degeneration (AMD).
Refresh me on this company.
As a biopharmaceutical company, Ocular Therapeutix is formulating, developing, and commercializing therapies for ophthalmic diseases and conditions via a proprietary bioresorbable hydrogel-based formulation technology.
The company’s first commercial drug product is DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, an FDA-approved corticosteroid intended for the treatment of ocular inflammation and pain post-ophthalmic surgery as well as ocular itching associated with allergic conjunctivitis.
Now talk about OTX-TKI.
OTX-TKI is an investigational, bioresorbable hydrogel intravitreal implant with anti-angiogenic properties and designed to continuously deliver axitinib (a potent tyrosine kinase inhibitor [TKI]) for wet AMD.
To note, it is also being developed for the potential treatment of diabetic retinopathy (DR) and other vascular endothelial growth factor (VEGF)-mediated retinal diseases.
How is the implant delivered?
The intravitreal implant delivers axitinib using Ocular Therapeutix’s proprietary Elutyx technology platform—a bioresorbable polymer matrix hydrogel developed to provide localized, sustained drug delivery.
OTX-TKI is administered via a 25G needle, with a target release of 9 to 12 months.
Gotcha … now give me the low-down on this trial.
The prospective, multi-center, randomized, controlled phase 1 study (NCT04989699) enrolled 21 patients (ages 50+; all previously treated with anti-VEGF therapy) across six U.S. clinical sites.
Participants were randomized 3:1 to an arm to receive either:
- A single OTX-TKI implant (600 μg dose) followed by a 2 mg aflibercept injection 4 weeks later (n = 16)
- Aflibercept injections every 8 weeks (n = 5)
Did all patients participate in the efficacy analysis?
Actually, no. One patient was removed from the OTX-TKI-treated group due to protocol deviation (they incorrectly received an aflibercept injection at Month 3 and 5 instead of a sham, as was intended).
So what was measured?
Primary outcomes included the safety, durability, and tolerability of OTX-TKI through 12 months.
Secondary outcomes were the assessment of participants’ biological activity, determined by measuring best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) of the retina.
And the 12-month findings?
A sustained BCVA was continuously noted for patients treated with the single OTX-TKI implant (mean change from baseline = -1.0 letters) as well as a sustained CSFT (mean change from baseline = +20.2 μm).
How did this compare to those treated with aflibercept?
The data was comparable, with aflibercept-treated arms showing a mean change from BCVA baseline of +2.0 letters and a mean change from CST baseline of -2.2 μm).
What else to know?
Up to 12 months, 60% of OTX-TKI-treated patients were rescue-free; an additional four patients were rescue-free at the 12-month mark.
Out of all OTX-TKI patients, an 89% reduction in treatment burden was observed over a 12-month period.
Any adverse reactions?
According to the company, as of April 14, 2023 (the data cutoff), no drug-related ocular or systemic serious adverse events (SAEs) were reported among patients with the OTX-TKI arm.
Per the previously-reported 10-month data (back in February 2023), one SAE of endophthalmitis was noted in the OTX-TKI arm at Month 1 following aflibercept injection.
Any expert input?
According to Arshad M. Khanani, MD, MA, principal investigator of the trial, an estimated 79% of patients required either no or only one supplemental anti-VEGF injection through Month 12, “which is clinically meaningful and highlights the possibility of OTX-TKI being widely adopted in the management of wet AMD.”
So what’s next?
Pending the requisite financing, Ocular Therapeutix plans to initiate a pivotal trial in wet AMD (potentially by Q3 of 2023).
Significance?
OTX-TKI has the potential to fill the unmet need for retinal disease treatment such as wet AMD with an efficacy that extends beyond three to four months administered by a single injection.