Clinical Trials

Date: 2017-05-09

Type of information: Completion of patient enrollment

phase: 3

Announcement: completion of patient enrollment

Company: Molecular Partners (Switzerland) Allergan (Ireland)

Product: abicipar pegol (anti-VEGF DARPin - AGN-150998/MP0112)

Action mechanism:

• protein/DARPIN. Abicipar pegol (MP0112) is a DARPin-based, small therapeutic protein, which inhibits all relevant forms of vascular endothelial growth factor A (VEGF-A) with high potency and selectivity. The molecule is under development for the treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME). Abicipar was exclusively licensed to Allergan/Actavis from Molecular Partners in May 2011.

Disease: wet age-related macular degeneration (wet AMD)

Therapeutic area: Ophtalmological diseases

Country: CEDAR: Argentina, Austria, Chile, Colombia, Czechia, France, Germany, Hong Kong, Israel, Republic of Korea, Latvia, New Zealand, Philippines, Singapore, Spain, Switzerland, USA - SEQUOIA: Australia, Brazil, Canada, Denmark, Hungary, Italy, Japan, Netherlands, Peru, Poland, Russian Federation, South Africa, Taiwan, Turkey, Uk, USA

Trial details:

• The phase 3 program includes two studies, CEDAR (NCT02462928) and SEQUOIA (NCT02462486), each planned to recruit 900 patients. The studies will evaluate the efficacy and safety of abicipar versus ranibizumab (Lucentis®) and the potential of abicipar to be dosed every 8 or 12 weeks vs. ranibizumab every 4 weeks. Top-line data are expected in 2018.

Latest news:

• • On May 9, 2017. Molecular Partners announced that its partner Allergan has completed the patient recruitment in the two global AMD Phase 3 studies of abicipar pegol. The phase 3 program includes two studies, CEDAR and SEQUOIA, each planned to recruit 900 patients. The studies will evaluate the efficacy and safety of abicipar versus ranibizumab (Lucentis®) and the potential of abicipar to be dosed every 8 or 12 weeks vs. ranibizumab every 4 weeks. Top-line data are expected in 2018.
• • On July 7, 2015, Molecular Partners announced that its partner Allergan has initiated phase III clinical trials with abicipar pegol (abicipar) for the treatment of wet age-related macular degeneration (wet AMD). The event triggered a clinical milestone payment to Molecular Partners of  $ 15 million.
• • On May 11, 2015, Molecular Partners announced that the new Actavis/Allergan management team has confirmed the abicipar phase III clinical program is on track to be initiated by the end of Q2 2015 or early in the third quarter. The phase III study program will evaluate the safety and efficacy of abicipar and its potential to improve vision gains whilst reducing the number of treatment injections versus ranibizumab (Lucentis®), addressing two significant unmet medical needs for patients with wet AMD. This is the first official announcement from Actavis/Allergan on abicipar following the companies’ merger in March.
• • On June 30, 2014, Allergan announced updates on one of its key R&D pipeline programs, including abicipar pegol (Anti-VEGF DARPin®). The company has completed the topline analysis of data from the Company's Stage 3, Phase 2 study of abicipar pegol (Anti-VEGF DARPin®) in neovascular, or "wet," age-related macular degeneration (AMD). These data along with data from previous studies were reviewed with the FDA at an end of a Phase 2 meeting where the FDA supported Allergan's decision to advance abicipar pegol to Phase 3 clinical trials and agreed with the proposed Phase 3 study plan.
• The abicipar pegol Stage 3, Phase 2 study was designed to, in addition to assessing safety and efficacy, determine the appropriate dose of abicipar pegol that would provide equal or better visual acuity improvement but require less frequent injections than ranibizumab (Lucentis®). In the double-masked trial, a total of 64 patients were randomized to abicipar pegol 1mg (n=25), abicipar pegol 2mg (n=23) or ranibizumab 0.5mg (n=16) and were followed for 20 weeks. All patients received doses at the start of the trial and at 4 and 8 weeks. Patients in the ranibizumab arm of the study received additional doses at 12 and 16 weeks. Patients who were treated with either dose of abicipar pegol received sham injections at 12 and 16 weeks. Patients in all arms of the study were well matched for demographics and baseline characteristics. The analysis of the topline data showed that after 16 weeks, mean visual acuity improvement from baseline was 8.2 letters for abicipar pegol 2mg, 6.3 letters for abicipar pegol 1mg, and 5.3 letters for ranibizumab. After 20 weeks, (12 weeks after the last abicipar injection and 4 weeks after the last ranibizumab injection) mean visual acuity improvement from baseline was 9.0 letters for abicipar pegol 2mg, 7.1 letters for abicipar pegol 1mg, and 4.7 letters for ranibizumab. In addition, Optical Coherence Tomography (OCT) data was supportive of the visual acuity data. Although the study was not powered to show statistically significant differences between treatment groups, and further data will be completed and submitted to the FDA, these data suggest that abicipar at the 2mg dose is at least as effective as monthly ranibizumab with a longer duration of action.
• There were no serious adverse events reported in any study group. Two patients in the abicipar pegol 2mg arm and three patients in the abicipar pegol 1mg group experienced ocular inflammation adverse events. The complete data from the Stage 3, Phase 2 study will be presented at a retina meeting in the second half of 2014.
• Allergan has been working to enhance the manufacturing process for abicipar pegol and will initiate Phase 3 studies in the second quarter of 2015, when material from the new manufacturing process is available. In the phase 3 program, Allergan will compare abicipar 2mg dosed every 8 weeks, abicipar 2mg dosed every 12 weeks and ranibizumab dosed every 4 weeks. All patients in the phase 3 program will receive three loading doses of drug.
• • On April 5, 2012, Molecular Partners has commented on the recent progress with its anti-VEGF DARPin (AGN 150998/MP0112), which is being developed in partnership with Allergan for ocular indications. Allergan has announced at their R&D day that the compound successfully completed phase IIa development. AGN-150998/MP0112 was shown to be safe and well tolerated, with no dose limiting toxicity, after a single administration. Further, preliminary efficacy results from this study suggest a dosing interval of up to 3 months. Based on these results, Allergan has  initiated a double-masked Phase IIb study comparing two high doses of AGN-150998/MP0112 with Lucentis, the current standard of care.

Is general: Yes