Allergan and Molecular Partners announced topline safety results from MAPLE, a 28-week open-label study which enrolled 123 age-related neovascular macular degeneration (AMD) patients and evaluated the safety of abicipar produced via a modified manufacturing process. In this single arm study, treatment naïve or prior anti-VEGF treated patients received three monthly 2mg abicipar injections followed by 2mg injections every 8 weeks for up to a total of five injections through week 28.
As a result of the improvements in the manufacturing process, the incidence of intraocular inflammation (IOI) was 8.9 percent in the MAPLE study, which was lower than the rate observed in prior phase 3 studies. Most IOI events were assessed as mild to moderate in severity. The incidence of severe IOI was 1.6 percent with one reported case of iritis and one reported case of uveitis. There were no reported cases of endophthalmitis or retinal vasculitis in this study.
“It is encouraging to see the lower incidence and type of IOI observed in this open label 28-week study,” Raj Maturi, MD, Midwest Eye Institute & Associate Professor Ophthalmology, Indiana University School of Medicine, said in a company news release. “In the phase 3 trials previously reported, abicipar demonstrated potential that could transform the way physicians manage nAMD with anti-VEGF therapy. Abicipar could be the first fixed 12- week anti-VEGF treatment that improves visual outcomes in a real world setting for a large number of AMD patients.“
Allergan expects to file the abicipar biologics license application (BLA) with the FDA in the first half of 2019. Additional data from the MAPLE study will be presented at a scientific conference later in 2019.
“The results of this open-label study enabled us to assess improvements to the manufacturing process for abicipar. The safety profile demonstrated in MAPLE gives us confidence to proceed and scale up manufacturing,” David Nicholson, Chief Research and Development Officer, Allergan, said in the news release. “We plan to submit the abicipar BLA and continue to pursue manufacturing process improvements as we develop larger scale studies in additional disease states, such as diabetic macular edema.”
“Clinical trial evidence has shown that fixed-interval dosing of anti-VEGF therapies administered either every month or every 8 weeks results in better visual outcomes compared to real world clinical outcomes. Abicipar could potentially be the first anti-VEGF therapy that is administered every 12 weeks with demonstrated maintenance of visual acuity for a large number of patients with nAMD. A fixed-interval Q12-week therapy would greatly reduce the treatment burden for these patients,” Peter Kaiser, MD, Chaney Family Endowed Chair in Ophthalmology Research and Professor of Ophthalmology, Cleveland Clinic Cole Eye Institute, said in the news release.
“Abicipar is our first DARPin candidate on track for BLA submission with the aim to become the first fixed 12-week anti VEGF drug in all patients with nAMD,” commented Michael T. Stumpp, COO of Molecular Partners. “The safety data from the MAPLE trial are an important step in the further improvement of the manufacturing process of abicipar.”
About ABICIPAR CEDAR and SEQUOIA PHASE 3 TRIALS
Allergan and Molecular Partners previously announced results from two positive phase 3 clinical trials, CEDAR and SEQUOIA for abicipar, a novel DARPin therapy for the treatment of nAMD, demonstrating that both the 8-week and 12-week fixed-interval treatment regimens met the pre-specified primary endpoint of noninferiority to ranibizumab. 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.
In the CEDAR study, overall treatment-emergent adverse events were similar among the three treatment arms and reported in 73.7 percent, 81.1 percent and 73.2 percent of patients receiving abicipar Q8, abicipar Q12 and ranibizumab Q4, respectively. Incidence of intraocular inflammation events was similar among the two abicipar treatment groups but higher than the ranibizumab group and reported at 15.1 percent and 15.4 percent of patients in the abicipar Q8 and Q12 arms compared to 0 percent in the ranibizumab Q4.
In the SEQUOIA study, overall treatment-emergent adverse events were similar among the three treatment arms and reported in 78.3 percent, 78.0 percent, and 74.0 percent of patients receiving abicipar Q8, abicipar Q12 and ranibizumab Q4, respectively. Incidence of intraocular inflammation events was similar among the two abicipar treatment groups but higher than the ranibizumab group and reported at 15.7 percent and 15.3 percent of patients in the abicipar Q8 and Q12 arms compared to 0.6 percent in the ranibizumab Q4 arm.