Allergan and Molecular Partners, partnering to develop a new class of drugs for retinal disease known as DARPin therapy (abicipar pegol), have released new data for 2 large-scale, phase 3 clinical trials, SEQUOIA and CEDAR, demonstrating that both the 8-week and 12-week treatment regimens met the prespecified primary endpoint of noninferiority to ranibizumab (Genentech).
SEQUOIA and CEDAR are identical global phase 3 studies designed to assess the efficacy and safety of abicipar compared with ranibizumab in treatment-naïve patients with wet AMD. The primary endpoint measured the proportion of treated patients with stable vision at week 52.
In both studies, abicipar demonstrated similar efficacy after 6 or 8 injections, compared to 13 ranibizumab injections in the first year of this study. However, intraocular inflammation in both the SEQUOIA and CEDAR trials totaled 15% of trial participants compared to 0.6% inflammation in the ranibizumab cohort. In the SEQUOIA study, the proportion of patients with stable vision in abicipar dosed every 8 weeks was 94.8%, stable vision with 12-week dosing was 91.3% compared to ranibizumab dosed every 4 weeks achieving 96.0% stable vision. In CEDAR, the proportion of patients with stable vision in the abicipar dosed every 8 weeks was 91.7% and 91.2% every 12 weeks, compared to ranibizumbab dosed every 4 weeks at 95.5% stable vision.
"In both studies abicipar demonstrated remarkable efficacy in the 8-week and 12-week regimens," said David Nicholson, Chief Research and Development Officer, Allergan, in a news release. "We are pleased with the outcome of these trials. We believe the SEQUOIA and CEDAR studies demonstrated what we set out to achieve, strong efficacy and duration of effect which shows the potential of abicipar as a treatment for AMD patients. We have generated important findings in these trials to address a serious unmet need. We will continue to review these data including inflammation findings and are working on further optimizing the abicipar formulation."
In regard to the incidence of inflammation, Yehia Hashad, MD, vice president and global head of clinical development, ophthalmology, said, "The incidence of inflammation was broadly in line with our phase 2 studies, such as in PALM for DME. We are working to get the incidence down by optimizing our manufacturing process in such areas as filtration. The inflammation was treated by the investigators as guided by their professional experience. The vast majority was mild-to-moderate."
Dr. Hashad also noted that abicipar "demonstrated a true 12-week retreatment cycle because patients won’t need OCT evaluations between treatments. This would reduce the overall burden of examinations and treatments."
The overall adverse events were similar among the 3 treatment arms. SEQUOIA and CEDAR clinical trials continue on a masked basis for a second year. The filing for abicipar is planned for the first half of 2019. Allergan will be requesting a meeting with the FDA to discuss its BLA submission.