Allergan, an AbbVie Company, and Molecular Partners, a clinical-stage biotechnology company developing a new class of custom-built protein therapeutics known as DARPin therapeutics, announced that the FDA has issued a complete response letter to the biologics license application (BLA) for abicipar pegol, a novel, investigational DARPin therapy with a fixed 12-week dosing period for patients with wet AMD. The letter from the FDA indicates that the rate of intraocular inflammation observed following administration of abicipar pegol 2mg/0.05 mL results in an unfavorable benefit-risk ratio in the treatment of wet AMD.

AbbVie says it plans to meet with the FDA to discuss their comments and determine next steps. Allergan and Molecular Partners worked hard to bring down the inflammation rate seen in the CEDAR and SEQUOIA phase 3 studies, but the improvement was not enough to acheive FDA approval. Inflammation rates improved for abicipar in the MAPLE study, a 28-week open-label study that enrolled 123 wet AMD patients and evaluated the safety of the DARPin produced via a modified manufacturing process. In this single-arm study, treatment-naïve or prior anti-VEGF-treated patients received 3 monthly 2 mg abicipar injections followed by 2 mg injections every 8 weeks for up to a total of 5 injections through week 28. As a result of the improvements in the manufacturing process, the companies reported that incidence of intraocular inflammation (IOI) was 8.9% in the MAPLE study, which was lower than the 15% 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%, with 1 reported case of iritis and 1 reported case of uveitis. There were no reported cases of endophthalmitis or retinal vasculitis in this study.

“We continue to believe in the need for treatment options that provide patients with reliable vision gains and less frequent dosing for the treatment of nAMD,” said Michael R. Robinson, MD, vice president and global therapeutic area head of ophthalmology at AbbVie. “We are committed to working with the FDA to determine the appropriate next steps for abicipar pegol.”