The U.S. Food and Drug Administration issued a Complete Response Letter, a rejection, of Allergan’s Biologics License Application for Abicipar pegol for neovascular age-related macular degeneration.
Abicipar pegol rejected by FDA
The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL), a rejection, of Allergan’s Biologics License Application (BLA) for Abicipar pegol for neovascular age-related macular degeneration (nAMD). Allergan is now an AbbVie Company.
The rejection appears to be related to safety concerns, although the company does not provide much information. It indicates that the FDA said the “rate of intraocular inflammation observed following administration of Abicipar pegol 2mg/0.06 mL results in an unfavorable benefit-risk ratio.”
AbbVie indicates it plans to meet with the agency to discuss the rejection and outline a plan for dealing with it.
“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, vice president, Global Therapeutic Area Head, Ophthalmology, AbbVie. “We are committed to working with the FDA to determine the appropriate next steps for Abicipar pegol.”
DARPin molecules come from naturally occurring binding proteins made up of repeat sequences with capping structures at each end of the protein. These molecules have three components that are important for researchers: high binding affinity, low molecular weight and customizable applications. DARPin stands for Designed Ankyrin Repeat Proteins. Abicipar pegol is made up of DARPin molecules. It binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF) factor A, which prevents neovascularization and vessel permeability in the eye.
The BLA was built on data from two identical Phase III trials, CEDAR and SEQUOIA. The studies both compared Abicipar pegol to Genentech’s Lucentis (ranibizumab) in treatment-naïve patients with nAMD. The primary endpoint for both trials was the percentage of patients with the best corrected visual acuity (BCVA) change from baseline less than or equal to 15 letters in the study eye at Week 52.
The data showed abicipar pegol to be noninferior with similar efficacy as Lucentis after six or eight injections compared to 13 Lucentis injections at 52 weeks. The overall adverse events were similar among all three treatment arms, although the FDA apparently didn’t agree.
Age-related macular degeneration (AMD) is an eye disease that blurs the middle section of vision. Wet AMD, or advanced neovascular AMD, is a serious form of AMD that occurs when VEGF creates too many blood in the back of the eye. These blood vessels can damage the macula, part of the eye. In general, the two treatments for wet AMD are anti-VEGF injections and photodynamic therapy (PDT). The most common treatment is anti-VEGF injections.
This is undoubtedly a blow to AbbVie, which completed its $63 billion acquisition of Allergan only about a month ago. And Abicipar pegol is one of the drugs that they hoped to be approved.
The drug was co-developed with Molecular Partners.
Another drug on the market is Regeneron’s Eylea (aflibercept). Both Eylea and Lucentis are blockbuster drugs, although biosimilars are expected to hit the market soon for them, which will likely squeeze the market for Genentech, Regeneron, and if AbbVie/Allergan can manage to resubmit and get an approval for Abicipar pegol, for them as well. Sell-side analysts have only projected Abicipar pegol as bringing in about $180 million per year.
Molecular Partners, on the other hand, took a hard hit, with its stock plunging 40% at the news this morning. Molecular Partners, based in Switzerland, inked the deal with Allergan for the drug back in 2011, with $1.5 billion in milestone payments riding on it.
