AngioLab announced the results of the phase 2 McEye study of ALS-L1023, an investigational drug to treat wet age-related macular degeneration (AMD).
The company explored the optimal dose of ALS-L1023 combined with ranibizumab (brand name: Lucentis) and evaluated the safety and efficacy in 126 patients with neovascular (wet) AMD at 11 medical institutions, including Samsung Medical Center.
The Konex-listed company received the Ministry of Food and Drug Safety’s approval for the phase 2 study in June 2015. However, the company changed the study protocol in 2016 and 2018 due to changes in the primary endpoint and additional stratification factors.
AngioLab randomly assigned patients into three groups in a 1:1:1 ratio – Group A (ranibizumab 0.5mg and ALS-L1023 600mg per day) or Group B (ranibizumab 0.5mg and ALS-L1023 1200mg per day) or Group C (ranibizumab 0.5mg and placebo per day).
Ranibizumab 0.5mg was injected into the vitreous every month for the first three months and injected or not injected depending on the criteria for re-administration later on. ALS-L1023 was given orally twice a day.
Randomization was stratified by whether or not the patient had polypoidal choroidal vasculopathy (PCV) at the screening test.
AngioLab assessed the drug’s efficacy in 95 patients who completed the trial and the safety in 126 patients.
The mean change of Best Corrected Visual Acuity (BCVA) at 12 months from baseline, set as the primary endpoint, was 11.58 letters in Group A, 4.11 letters in Group B, and 7.23 letters in Group C.
In Group A and C, BCVA increased at 12 months from baseline, and Group A improved by 4.35 letters compared to the control Group C.
However, each treatment group and the control group did not significantly differ in BCVA changes.
The sub-group analysis based on PCV presence showed that Group A among patients without PCV improved by 14.44 letters, Group B, four letters, and Group C, 5.22 letters. In addition, BCVA at 12 months from baseline increased, and Group A improved by 9.22 letters compared to Group C.
However, in Group B, the maximum BCVA at baseline was significantly higher than the control group. So, the company could not confirm dose-dependent effects.
The analysis of treatment-emergent adverse events (TEAEs) after ALS-L1023 administration showed that the occurrence of TEAEs was not statistically significant between treatment groups. In addition, most side effects were mild and not related to the treatment.
Adverse drug reactions (ADRs) were similar among treatment groups, and no serious adverse event or ADR leading to death occurred.
In the secondary endpoints, the proportion of patients who showed visual acuity improvement by three lines or more (15 letters) was significantly higher in Group A than in the control group. Statistical significance was also confirmed in those without PCV compared to the control group, AngioLab said.
However, the company could not find the effect in other outcomes because the study was an exploratory one, and the number of patients was too small to evaluate statistical effectiveness, the company went on to say.
“As the BCVA at baseline in Group B was higher than that of the control group, we could not confirm the dose-dependent improvement effect,” it said.
In the phase 2 trial, the company confirmed ALS-L1023’s benefit in visual improvement compared to ranibizumab, which inhibits only VEGF.
Also, it added that there was significant efficacy in non-PCV patients compared to the control group. “Existing wet AMD treatments are expensive and should be injected into the eye, while ALS-L1203 is an oral drug that can improve visual acuity when administered with a small number of ranibizumab injections,” AngioLab said.
Based on these findings, the company plans to seek a licensing-out deal and conduct an additional ALS-L1023 study with a larger number of subjects.
According to AngioLab, ALS-L1023 inhibits angiogenic factors such as VEGF, bFGF, PDGF, and MMP simultaneously and protects retinal pigment epithelial cells from oxidative stress-induced apoptosis.