Ocular Therapeutix, Inc. announced in a press release additional positive Week 52 data from the SOL-1 phase 3 superiority trial of Axpaxli (OTX-TKI), its investigational product candidate for the treatment of wet age-related macular degeneration (wet AMD). According to the company, the additional post hoc analyses presented at the 14th Annual Vit-Buckle Society Meeting reinforce the durability, strong sustained disease control, and generally well-tolerated safety seen with Axpaxli in SOL-1.

The data presented showed a strong overall efficacy profile with durability—statistical significance was achieved in the first 3 of 5 key secondary endpoints tested in hierarchical order. In addition, 6 other pre-specified secondary endpoints measuring clinically significant functional and anatomic outcomes were met with statistical significance, the company said. 

Regarding sustained disease control (post hoc analysis),subjects in the Axpaxli arm had significantly lower risk in anatomic worsening from Week 8 compared to the aflibercept (2 mg) arm. Week 8 was chosen to give both arms adequate time from the last aflibercept (2 mg) injection and start at a similar reference timepoint, the company explained in the press release.

Ocular Therapeutix noted that the median time to ≥30 uM central subfield thickness (CSFT) increase from Week 8 was 39 weeks in the Axpaxli group and 16 weeks in the aflibercept (2 mg) group, a 23-week difference. An estimated hazard ratio of 0.7 indicates that, at any time from Week 8 to Week 52, subjects in the treatment group experienced a 30% lower risk of the event (descriptive p=0.0028) compared with the control group, the company said.

The median time to ≥75 uM CSFT increase from Week 8 was 46 weeks in the Axpaxli group and 24 weeks in the aflibercept (2 mg) group, a 22-week difference. An estimated hazard ratio of 0.5 indicates that, at any time from Week 8 to Week 52, subjects in the treatment group experienced a 50% lower risk of the event (descriptive p<0.0001) compared with the control group.

Regarding sustained visual outcomes (post-hoc analysis), the company also noted that visual acuity gains achieved during the loading phase were generally maintained up to Week 52 with Axpaxli across screening best-corrected visual acuity (BCVA) quartile subgroups. The magnitude of vision improvements was influenced by BCVA at screening. For example, Axpaxli subjects in the lowest vision quartile group at screening had the greatest visual gains with +11.8 ETDRS letters compared to +8.5 letters in the aflibercept (2 mg) arm at Week 52. The mean vision at screening in this arm is similar to baseline BCVA in prior wet AMD studies. In comparison, subjects in the best vision quartile at screening had essentially no change in vision at Week 52 (-0.5 vs +1.1 letters; Axpaxli vs aflibercept) as they started with almost 20/20 vision, the company said.

Regarding sustained visual outcomes in rescue-free subjects (post-hoc analysis), the observed difference for change in BCVA from baseline at Week 24 in the rescue-free subjects was -1.9 ETDRS letters in the Axpaxli arm (+7.5 letters from screening) vs -2.6 letters in the aflibercept arm (+6.0 letters from screening). Of note, 81% of the Axpaxli subjects were rescue-free at Week 24. At Week 36, 75% of Axpaxli subjects remained rescue-free and lost <1 additional letter from Week 24 (+6.6 letters from screening).

According to the company, for all Axpaxli subjects with a vitreous floater adverse event reported, drug particles are no longer visible (mean time of 20 weeks). Further analysis continues to illustrate the appearance of floaters corresponds closely to expected hydrogel bioresorption and drug elution without adversely affecting vision.

"New analyses from our landmark SOL-1 phase 3 trial continue to reinforce our conviction that OTX-TKI demonstrates a level of unmatched durability and sustained disease control that is truly unprecedented in wet AMD treatment," said Pravin Dugel, MD, executive chairman, president, and CEO of Ocular Therapeutix. "For retina specialists, OCT-based anatomic control is central to treatment decision-making, and the time-to 30 uM and 75 uM CSFT increase analyses presented at VBS provide particularly striking evidence, representing an extraordinarily prolonged period of anatomic stability that we simply have not seen before."

Dr. Dugel continued, "just as importantly, a high proportion of patients (68.8%) remained rescue-free per protocol at 1 year, demonstrating the potential to address a critical challenge in the management of wet AMD, where frequent injections cause a heavy treatment burden and threaten patient adherence. Taken together, these data underscore how OTX-TKI could transform clinical practice by reducing treatment burden while maintaining long-term, sustained disease control."

Ocular Therapeutix said it remains on track to submit its new drug application for Axpaxli in wet AMD based on the SOL-1 trial alone, and is subject to planned formal discussions with the US Food and Drug Administration (FDA). RP