Iveric bio announced positive 18 month results from the company’s first phase 3 clinical trial for Zimura (avacincaptad pegol), a novel complement C5 inhibitor, for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
The 18 month data supports the previously announced 12 month data from this trial, at which time point Zimura met the prespecified primary efficacy endpoint with statistical significance. The reduction in the mean rate of GA growth over 18 months was 28.11% for the Zimura 2 mg group as compared to the corresponding sham control group and 29.97% for the Zimura 4 mg group as compared to the corresponding sham control group. The prespecified efficacy analysis for the primary endpoint was performed at month 12 using all of the power in the trial to detect a statistically significant difference. Therefore, the p-values for the 18 month statistical analyses are descriptive in nature. The descriptive p-values for the treatment effects at month 18 were P=0.0014 for the Zimura 2 mg group and p=0.0021 for the Zimura 4 mg group.
In this trial, the treatment effect was observed as early as 6 months, with an increase in the absolute difference of the mean change in GA growth for treatment with either Zimura 2 mg or Zimura 4 mg, as compared to sham, at each subsequent time point, suggesting the progressive benefit of continuous treatment with Zimura. Zimura maintained its favorable safety profile at 18 months with no reported Zimura related adverse events, no cases of endophthalmitis and a lower rate of choroidal neovascularization (CNV) than reported for C3 inhibition. The overall 18 month data may suggest a dose response relationship.
“We are extremely excited by the new 18 month data from this Phase 3 clinical trial, both with respect to efficacy and safety,” Glenn P. Sblendorio, Chief Executive Officer and President of Iveric bio, said in a company news release. “In the OPH2003 clinical trial, the 18 month results indicated continuous Zimura treatment benefit with a favorable safety profile in patients with GA secondary to AMD. This is an impressive achievement since we believe OPH2003 is currently the only phase 3 clinical trial showing suppression of GA growth with continuous treatment for 18 months.”
“We are one step closer to potentially bringing a clinically meaningful therapy to patients with GA who currently do not have any FDA or EMA approved treatments available to them,” stated Kourous A. Rezaei, MD, Chief Medical Officer of Iveric bio. “We believe the robust 18 month efficacy data further validates the potential role of complement C5 inhibition in GA secondary to AMD and has the potential to differentiate Zimura from other product candidates in development. We are poised to initiate our second pivotal trial, ISEE2008, comparing Zimura 2 mg with sham later this month. We want to thank our patients, our clinical trial investigators and their staffs for their support and participation in this trial.”
The company previously announced that in the OPH2003 clinical trial, Zimura met its prespecified primary efficacy endpoint at 12 months and reached statistical significance in the international, multicenter, randomized, double masked, sham controlled clinical trial in GA secondary to AMD. The reduction in the mean rate of GA growth over 12 months was 27.38% (P= 0.0072) for the Zimura 2 mg group as compared to the corresponding sham control group and 27.81% (P=0.0051) for the Zimura 4 mg group as compared to the corresponding sham control group. The data for both dose groups were statistically significant.
ITT Population; Based on the least squares means from MRM Model drawing on all available data at the respective 12 month and 18 month analysis time points, including data from groups with different randomization ratios in Part 1 and Part 2, and should not be interpreted as directly observed data; Hochberg procedure used for significance testing for 12 month data. *Previously reported (PRNewsfoto/IVERIC bio, Inc.)
“I am excited about the efficacy and favorable safety profile observed in the 12 month Zimura phase 3 data, and now the long term 18 month efficacy and safety data further confirm my belief in the role of complement C5 inhibition in the treatment of GA,” Peter K. Kaiser, MD, Chaney Family Endowed Chair in Ophthalmology Research, Cole Eye Institute and Professor of Ophthalmology at the Cleveland Clinic Lerner College of Medicine, said in a company news release. “The delta between the Zimura 2 mg and Zimura 4 mg treatment groups and the corresponding sham control groups occurred early in the study and continued over 18 months which means my patients may benefit after only a few injections and maintain this with additional treatments. Moreover, the safety profile remained favorable after 18 months of treatment.”
“We are excited by these 18 month results,” stated Pravin U. Dugel, MD, Executive Vice President and Chief Strategy and Business Officer of Iveric bio. “In the challenging COVID-19 pandemic era, we believe that we are in an advantageous position as the OPH2003 data is the only positive Phase 3 clinical data in GA secondary to AMD that we are aware of that has been reported to date. We believe that these robust data should increase investigator enthusiasm and confidence for patient recruitment and retention in our ISEE2008 clinical trial.”
Zimura was generally well tolerated after 18 months of administration. There was no Zimura-related inflammation, no Zimura-related discontinuations from the trial, no cases of endophthalmitis and no Zimura-related adverse events. Through month 18, the reported incidence of CNV in the untreated fellow eye was 11 patients (3.8%), and in the study eye was 3 patients (2.7%) in the sham control group, 8 patients (11.9%) in the Zimura 2 mg group, and 13 patients (15.7%) in the Zimura 4 mg group. The most frequently reported ocular adverse events were related to the injection procedure.
The company plans to make additional supportive information regarding the 18 month results available in its public filings with the Securities and Exchange Commission.
OPH2003 18 Month Data
A total of 286 patients were enrolled in this trial.
Mean rate of change in GA growth over 18 months, was measured by fundus autofluorescence (FAF) based on readings at four time points (baseline, month 6, month 12 and month 18) and was calculated using the square root transformation of the GA area. The FAF images were assessed by an independent masked reading center. The prespecified statistical analysis plan used a model of repeated measures (MRM) to compare data for the Zimura 2 mg and Zimura 4 mg groups to the corresponding sham groups.