Angiogenesis 2023: Ocular Therapeutix announces data from phase 1 clinical trial evaluating OTX-TKI for treatment of Wet AMD

According to Ocular Therapeutix Inc., the results demonstrated maintenance of controlled wet AMD subjects for up to 10 months with a single administration of OTX-TKI. (Adobe Stock Image)

Ocular Therapeutix Inc. on Saturday announced interim 10-month data from its U.S. Phase 1 clinical trial evaluating OTX-TKI, the company’s axitinib intravitreal hydrogel implant being developed for the treatment of wet age-related macular degeneration (wet AMD), diabetic retinopathy and other retinal diseases.

The data was presented at the Angiogenesis, Exudation, and Degeneration 2023 Virtual Meeting by Andrew A. Moshfeghi, MD, MBA.

“We are very pleased to see this latest 10-month data that support OTX-TKI's potential to set a new standard for durability in the treatment of wet AMD,” said Antony Mattessich, president and CEO of Ocular Therapeutix. “We have a product candidate designed to continuously deliver axitinib, a TKI with the highest binding affinity for the VEGF receptor currently in clinical development for the treatment of wet AMD and other VEGF-mediated retinal diseases.”

Mattessich pointed out that the results demonstrated maintenance of controlled wet AMD subjects for up to 10 months with a single administration of OTX-TKI.

“We intend to discuss with the FDA future clinical trial requirements and will plan to initiate a first pivotal trial for OTX-TKI in the third quarter of this year, subject to financing including a potential strategic alliance,” he added. “We are very excited for what these data could mean for patients suffering from any VEGF-mediated retinal disease – such as wet AMD, diabetic macular edema or diabetic retinopathy.”

Summary of Interim 10-month data

The company noted in its news release that the trial is designed to assess the safety, durability and tolerability of OTX-TKI. (Adobe Stock image)

According to the company, the ongoing U.S.-based Phase 1 clinical trial is a prospective, multi-center, randomized, controlled study in subjects previously treated with anti-VEGF therapy that is evaluating a 600 µg dose of OTX-TKI in a single implant, with a 2 mg aflibercept injection four weeks after the implant, compared to 2 mg aflibercept injections administered every 8 weeks.

The company noted in its news release that the trial is designed to assess the safety, durability and tolerability of OTX-TKI, and to assess biological activity in subjects by measuring best corrected visual acuity (BCVA) and central subfield thickness (CSFT) of the retina.

Moreover, the clinical trial enrolled a total of 21 subjects at six clinical sites in the U.S., who were randomized 3:1 to an arm receiving a single OTX-TKI implant, with a 2 mg aflibercept injection after implant, and an arm receiving aflibercept injections every 8 weeks. One subject in the OTX-TKI arm was not treated per protocol and has been removed from the efficacy analysis, as the subject incorrectly received aflibercept instead of a sham injection at Month 3 and 5 visits.

As of the data cutoff of December 12, 2022, in the U.S.-based Phase 1 clinical trial, the single OTX-TKI implant continued to be generally well tolerated with no drug-related ocular or systemic serious adverse events (SAEs) observed through 10 months. As the Company previously announced at the 7-month readout, one SAE of endophthalmitis was observed in the OTK-TKI arm which occurred following the mandated aflibercept injection at Month 1 and was assessed by the investigator as related to the injection procedure. There were no elevated IOP, retinal detachment, retinal vasculitis, or implant migration into the anterior chamber adverse events observed in the OTX-TKI arm, and no subjects had dropped out of either arm as of the data cutoff.

The interim results showed subjects treated with a single OTX-TKI implant demonstrated stable and sustained BCVA (mean change from baseline of -0.3 letters) and CSFT (mean change from baseline of -1.3 µm) in the OTX-TKI arm at 10 months, which was comparable with the aflibercept arm (mean change from BCVA baseline of -0.8 letters; mean change from CSFT baseline of -4.5 µm). The 73% of subjects who were rescue-free up to Month 7, continued to demonstrate OTX-TKI’s extended duration of action and remained rescue-free up to Month 10. Overall, a 92% reduction in treatment burden was observed in OTX-TKI treated subjects for up to 10 months.

“We are very encouraged by the interim 10-month data being presented that builds upon the interim 7-month data shared last year at the American Academy of Ophthalmology 2022 Annual Meeting,” Rabia Gurses-Ozden, MD, chied medical officer of Ocular Therapeutix, said in a news release. “OTX-TKI has been observed to generally be well tolerated with no serious drug-related ocular or systemic adverse events and the visual acuity and retinal thickness outcomes of subjects receiving OTX-TKI in the Phase 1 clinical trial have been comparable to those of subjects receiving aflibercept, while having a substantial reduction in treatment burden.”

“Efficacious treatment options are available for our patients with wet AMD, but there is a big unmet need for a treatment that can be effective for more than 3 to 4 months with a single injection. The reduction in treatment burden seen over the first 10 months in patients in the OTX-TKI U.S. Phase 1 clinical trial who previously required many injections is very exciting,” said BEDFORD, Mass., Feb. 11, 2023 (GLOBE NEWSWIRE) -- Ocular Therapeutix, Inc. (NASDAQ:OCUL), a biopharmaceutical company focused on the formulation, development, and commercialization of innovative therapies for diseases and conditions of the eye, today announced interim 10-month data from its U.S. Phase 1 clinical trial evaluating OTX-TKI, the Company’s axitinib intravitreal hydrogel implant being developed for the treatment of wet age-related macular degeneration (wet AMD), diabetic retinopathy and other retinal diseases. The data is being presented this morning at 8:00 am ET at the Angiogenesis, Exudation, and Degeneration 2023 Virtual Meeting by Andrew A. Moshfeghi, MD, MBA. The presentation can be accessed by visiting the scientific and medical presentations tab of the investor section of the Company’s website at investors.ocutx.com.

“We are very pleased to see this latest 10-month data that support OTX-TKI's potential to set a new standard for durability in the treatment of wet AMD,” said Antony Mattessich, President and Chief Executive Officer. “We have a product candidate designed to continuously deliver axitinib, a TKI with the highest binding affinity for the VEGF receptor currently in clinical development for the treatment of wet AMD and other VEGF-mediated retinal diseases. These results demonstrated maintenance of controlled wet AMD subjects for up to 10 months with a single administration of OTX-TKI. We intend to discuss with the FDA future clinical trial requirements and will plan to initiate a first pivotal trial for OTX-TKI in the third quarter of this year, subject to financing including a potential strategic alliance. We are very excited for what these data could mean for patients suffering from any VEGF-mediated retinal disease – such as wet AMD, diabetic macular edema or diabetic retinopathy.”

Summary of Interim 10-month Data from the Ongoing U.S. Phase 1 Clinical Trial Evaluating OTX-TKI for the Treatment of Wet AMD

The ongoing U.S.-based Phase 1 clinical trial is a prospective, multi-center, randomized, controlled study in subjects previously treated with anti-VEGF therapy that is evaluating a 600 µg dose of OTX-TKI in a single implant, with a 2 mg aflibercept injection four weeks after the implant, compared to 2 mg aflibercept injections administered every 8 weeks. The trial is designed to assess the safety, durability and tolerability of OTX-TKI, and to assess biological activity in subjects by measuring best corrected visual acuity (BCVA) and central subfield thickness (CSFT) of the retina. The clinical trial enrolled a total of 21 subjects at six clinical sites in the U.S., who were randomized 3:1 to an arm receiving a single OTX-TKI implant, with a 2 mg aflibercept injection after implant, and an arm receiving aflibercept injections every 8 weeks. One subject in the OTX-TKI arm was not treated per protocol and has been removed from the efficacy analysis, as the subject incorrectly received aflibercept instead of a sham injection at Month 3 and 5 visits.

As of the data cutoff of December 12, 2022, in the U.S.-based Phase 1 clinical trial, the single OTX-TKI implant continued to be generally well tolerated with no drug-related ocular or systemic serious adverse events (SAEs) observed through 10 months. As the Company previously announced at the 7-month readout, one SAE of endophthalmitis was observed in the OTK-TKI arm which occurred following the mandated aflibercept injection at Month 1 and was assessed by the investigator as related to the injection procedure. There were no elevated IOP, retinal detachment, retinal vasculitis, or implant migration into the anterior chamber adverse events observed in the OTX-TKI arm, and no subjects had dropped out of either arm as of the data cutoff.

The interim results showed subjects treated with a single OTX-TKI implant demonstrated stable and sustained BCVA (mean change from baseline of -0.3 letters) and CSFT (mean change from baseline of -1.3 µm) in the OTX-TKI arm at 10 months, which was comparable with the aflibercept arm (mean change from BCVA baseline of -0.8 letters; mean change from CSFT baseline of -4.5 µm). The 73% of subjects who were rescue-free up to Month 7, continued to demonstrate OTX-TKI’s extended duration of action and remained rescue-free up to Month 10. Overall, a 92% reduction in treatment burden was observed in OTX-TKI treated subjects for up to 10 months.

“We are very encouraged by the interim 10-month data being presented that builds upon the interim 7-month data shared last year at the American Academy of Ophthalmology 2022 Annual Meeting,” said Rabia Gurses-Ozden, MD, Chief Medical Officer. “OTX-TKI has been observed to generally be well tolerated with no serious drug-related ocular or systemic adverse events and the visual acuity and retinal thickness outcomes of subjects receiving OTX-TKI in the Phase 1 clinical trial have been comparable to those of subjects receiving aflibercept, while having a substantial reduction in treatment burden.”

Arshad M. Khanani, MD, MA, director of Clinical Research at Sierra Eye Associates, pointed out that efficacious treatment options are available for patients with wet AMD, but there is a big unmet need for a treatment that can be effective for more than 3 to 4 months with a single injection.

“The reduction in treatment burden seen over the first 10 months in patients in the OTX-TKI U.S. Phase 1 clinical trial who previously required many injections is very exciting,” Khanani said in the news release. “The data from the current trial is promising as 73% of the treated subjects were rescue-free up to Month 10. A drug with this durability would open up new opportunities in the treatment of retinal diseases.”

According to the news release, the company plans to meet with the FDA to discuss potential future clinical trial requirements. Subject to those discussions and obtaining the necessary financing, which could be provided through a strategic alliance, the company intends to initiate a pivotal trial in wet AMD in the third quarter of 2023.

Per protocol, the company will continue to follow subjects in the Phase 1 trial at least until their respective one-year anniversaries of initial dosing. Given the potential broad applicability of OTX-TKI to other retinal diseases, the Company initiated a U.S.-based Phase 1 clinical trial to evaluate OTX-TKI for the treatment of diabetic retinopathy in December 2022.

The data from the current trial is promising as 73% of the treated subjects were rescue-free up to Month 10. A drug with this durability would open up new opportunities in the treatment of retinal diseases.”

The company noted in its news release that it plans to meet with the FDA to discuss potential future clinical trial requirements. Subject to those discussions and obtaining the necessary financing, which could be provided through a strategic alliance, the company intends to initiate a pivotal trial in wet AMD in the third quarter of 2023.

Per protocol, the company said in the news release it will continue to follow subjects in the Phase 1 trial at least until their respective one-year anniversaries of initial dosing. Given the potential broad applicability of OTX-TKI to other retinal diseases, the company initiated a U.S.-based Phase 1 clinical trial to evaluate OTX-TKI for the treatment of diabetic retinopathy in December 2022.