The FDA sent a complete response letter (CRL) to Allergan plc, an Abbvie Inc. company, and Molecular Partners AG, of Zurich, Switzerland, regarding the BLA for abicipar pegol, their VEGF-A inhibitor-Darpin therapy for patients with wet age-related macular degeneration (AMD).
In the letter, the FDA noted the rate of intraocular inflammation occurring after administering abicipar pegol 2 mg/0.05 mL results in an unfavorable benefit-risk ratio. Abbvie said it will meet with the FDA to discuss the comments and determine next steps.
Molecular Partners’ stock (SIX:MOLN) dropped 31.73% Friday.
Molecular Partners’ Darpin molecules come from naturally occurring binding proteins with a high binding affinity and low molecular weight. The molecules are being developed to treat indications in ophthalmology, oncology and immune-oncology.
SVB Leerink’s Geoffrey C. Porges wrote Friday that he had “very low expectations for this product in terms of its regulatory and commercial pathway, given other better and safer treatment options, and a demanding standard of care for retinal diseases.” The likelihood of the Darpin product’s commercial launch now “goes from remote to impossible,” he continued, and he expects Abbvie to discontinue other Darpin trials, including a phase II diabetic macular edema study that’s currently underway, abandoning the application and writing off the development program.
Porges wrote that does not believe that this was a significant element of Abbvie’s Allergan acquisition and he expects the associated write-off to be modest, he concluded.
Abbvie, of North Chicago, completed its acquisition of Dublin-based Allergan in May. Allergan shareholders received 0.8660 Abbvie shares and $120.30 in cash for each Allergan share.
In September, Allergan and Molecular Partners said the FDA had accepted the BLA and the EMA validated a marketing authorization application for treating wet AMD. The companies expect action from the EMA in the second half of this year.
Both applications were based on data from two identical phase III trials, Cedar and Sequoia, assessing the efficacy and safety of abicipar compared with Lucentis (ranibizumab, Roche Holding AG) in treatment-naïve patients with wet AMD. The primary endpoint measured the proportion of treated patients with stable vision at week 52. In both studies, abicipar demonstrated similar efficacy after six or eight injections, compared to 13 ranibizumab injections in the study’s first year.
Intraocular inflammation was the concern noted in the FDA’s CRL. In July 2018, Molecular Partners noted that intraocular inflammation was higher in the abicipar arms compared to ranibizumab-treated patients in both trials.
“We will continue to review these data including inflammation findings and are working on further optimizing the abicipar formulation,” the company said.
Through week 104, patients received abicipar 2 mg every eight weeks or every 12 weeks or ranibizumab 0.5 mg every four weeks. At week 104 in the pooled phase III data, the proportion of patients with stable vision was 93%, 90% and 94% in eight-week abicipar, 12-week abicipar and four-week ranibizumab treatment regimens, respectively. The continuation of stable vision in year two further reinforces the ability of abicipar to deliver consistent quarterly dosing for the majority of patients, the companies said.
The overall adverse events were similar among the three treatment arms, with abicipar dosed every eight weeks, abicipar dosed every 12 weeks or ranibizumab dosed monthly.
The company is also developing a COVID-19 treatment. In April, Molecular Partners said it identified multiple potent monospecific Darpin proteins that neutralize samples of the SARS-CoV-2 virus. The company engineered the proteins into trispecific antiviral candidates targeting three parts of the viral spike protein, which is needed for viral entry into human cells. Multispecific inhibition represents a differentiated approach to treating COVID-19, offering potentially greater therapeutic efficacy and reduced potential for the development of viral drug resistance, the company added.