Abicipar pegol (Allergan Inc, Switzerland) is an anti-Vascular Endothelial Growth Factor (VEGF) molecule intravitreal injection that has not been approved by the FDA (Food and Drug Administration). It has gone through several clinical trials to determine its efficacy and safety in treating neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). DME and nAMD are leading causes of blindness that are commonly treated with anti-VEGF injections.
Mechanism of Action
Abicipar Pegol is an anti-VEGF molecule that binds to VEGF-A with high affinity. Vascular Endothelial Growth Factor (VEGF) is a molecule that binds to receptors and leads to immature vessel growth. In order to prevent the action of VEGF, Abicipar pegol binds to VEGF, disrupting its ability to bind to the VEGF receptor.
Abicipar pegol is a designed ankyrin repeat protein (DARPin) (Molecular Partners AG, Switzerland). This is a new class of proteins that is under investigation for use in treatment in a variety of diseases and illnesses, specific in oncology, immunology and ophthalmology. DARPins consist of four to six ankyrin protein repeats and have a right-handed helical structure. They contain a hydrophobic core and a binding surface that is large and grooved. DARPins have a low molecular weight and are rapidly cleared by the kidneys. Therefore, a poly-ethylene glycol tail was added to Abicipar pegol to reduce some of its clearance.
Adverse events that have been reported in clinical studies include intraocular information, including iritis, uveitis, vitritis, and choroiditis. Other adverse events include vitreous floaters, vitreous detachment, retinal hemorrhage, eye pain, and conjunctival hemorrhage.
Reach is a 20 week Phase II multicenter, double-masked clinical trial of 64 patients with neovascular age-related macular degeneration. The patients were randomized into three cohorts: Abicipar 1 mg, Abicipar 2 mg, and Ranibizumab 0.5 mg. Patients in the Abicipar groups received 3 injections: baseline, week 4, and week 8. Patients in the Ranibizumab group received 5 injections: baseline and monthly. At 20 weeks, the best-corrected visual acuity (BCVA) changes were +8.2, +10.0, and +5.3 letters for each group, respectively. At 20 weeks, the decrease in central retinal thickness (CRT) were 116 µm, 103 µm, and 138 µm for each group, respectively. The conclusion of this trial was that improvements BCVA and CRT were similar in the 3 groups, demonstrating efficacy of Abicipar.
BAMBOO & CYPRESS
Bamboo and Cypress are 20 week phase II multicenter, randomized, double masked studies of 25 patients each with neovascular age-related macular degeneration who have not been previously treated. The Bamboo trial took place in Japan, and the Cypress trial took place in the United States. Both trials had three randomized cohorts: Abicipar 1 mg, Abicipar 2 mg, and Ranibizumab 0.5 mg. Patients in the Abicipar groups received 3 monthly injections. Patients in the Ranibizumab group received 5 monthly injections.
In Bamboo, best-corrected visual acuity (BCVA) changes were +7.8, +8.9, and +17.4 letters for each group respectively. In Cypress, BCVA changes were +4.4, +10.1, and +15.2 letters for each group respectively. In Bamboo, the decrease in central retinal thickness (CRT) were 187.3 µm, 196.5 µm, and 230.4 µm for each group respectively. In Cypress, the decrease in central retinal thickness (CRT) was 106.5 µm, 112.8 µm, and 124.4 µm for each group respectively. Because of the small number of participants in this study, there are questions regarding whether the results have external validity.
Palm is a 28 week phase II double masked trial of 151 patients with Diabetic Macular Edema. The patients were randomized into four cohorts: Abicipar 1 mgQ8, Abicipar 2 mgQ8, Abicipar 2 mgQ12, and Ranibizumab 0.5 mgQ4. At 28 weeks, the mean changes in best-corrected visual acuity (BCVA) were +4.9, +7.1, +7.2 and +9.6, respectively. The mean changes in central retinal thickness (CRT) were -176.4 µm, -162 µm, -159.4 µm, and -158.8 µm, respectively.
SEQUOIA & CEDAR
Sequoia and Cedar are 52 week global, multicenter, randomized phase III studies of patients with neovascular age-related macular degeneration who have not been previously treated. Sequoia had 946 patients, and Cedar had 939 patients. In each study, the patients were randomized in three cohorts: Abicipar 2 mg q12w, Abicipar 2 mg q8w, and Ranibizumab 0.5mg q4w. At 52 weeks, the proportion of patients with stable vision in each cohort were evaluated. In Sequioa, the proportions were 91.3%, 94.8%, and 96.0%, respectively. In Cedar, the proportions were 91.2%, 91.7%, and 95.5%.
In both studies, treatment-emergent adverse events were comparable in the three cohorts. However, intraocular inflammation was higher in the two Abicipar groups when compared to the Ranibizumab group. In Sequoia, intraocular inflammation events were reported in 15.3% in the q12 group and 15.3% in the q8 groups but only 0.6% in the Ranibizumab group. In Cedar, intraocular inflammation was reported in 15.4% in the q12 group and 15.1% in the q8 groups but 0% in the Ranibizumab group.
Maple is a 28 week open label safety study of 123 patients with neovascular age-related macular degeneration. Patients received a monthly 2 mg Abicipar injection for three months and then received a 2 mg injection every 8 weeks for up to a total of 5 injections at the 28 week mark. Intraocular inflammation events occurred in 8.9% of the patients, which is a decrease compared to the prior phase III studies. Severe intraocular inflammation occurred in 1.6% of patients with one case of iritis and one cause of uveitis. No cases of endophthalmitis or retinal vasculitis were reported.
- Sharma A, Kumar N, Kuppermann BD, Bandello F. Abicipar pegol: the non-monoclonal antibody anti-VEGF. Eye (Lond). 2020;34(5):797-801. doi: 10.1038/s41422-019-0607-8
- Callanan D, Kunimoto D, Maturi RK, et al. Double-maksed, randomized phase 2 evaluation of abicipar pegol (an anti-VEGF DARPin therapeutic) in neovascualr age-related mecular degeneration. J Ocul Pharmacol Ther. 2018;34(10):700-709. doi: 10.1089/jop.2018.0062
- Kunimoto D, Ohji M, Maturi RK, et al. Evaluation of abicipar pegol (an anti-VEGF DARPin therapeutic) in patients with neovascular age-related macular degeneration: Studies in Japan and the United States. Ophthalmic Surg Lasers Imaging Retina. 2019;50(2):e10-e22. doi: 10.3928/23258160-20190129-13.
- Molecular Partners. Abicipar pegol PALM study phase 2 data in diabetic macular edema (DME) presented at 2016 AAO annual meeting. Molecular Partners. https://www.molecularpartners.com/abicipar-pegol-palm-study-phase-2-data-in-diabetic-macular-edema-dme-presented-at-2016-aao-annual-meeting/. Accessed July 14, 2023.
- Molecular Partners. Allergan and molecular partners announce two positive phase 3 clinical trials for abicipar pegol 8 and 12 week regimens for the treatment in patients with neovascular age-related macular degeneration. Molecular Partners. https://investors.molecularpartners.com/news-releases/news-release-details/allergan-and-molecular-partners-announce-two-positive-phase-3. Accessed July 14, 2023.
- Molecular Partners. Allergan and molecular partners announce topline safety results from maple study of abicipar pegol. Molecular Partners. https://investors.molecularpartners.com/news-releases/news-release-details/allergan-and-molecular-partners-announce-topline-safety-results. Accessed July 14, 2023