Fewer New Cases of Intraocular Inflammation After First Year of Abicipar in AMD Patients

By Reuters Staff

December 28, 2020

NEW YORK (Reuters Health) - Most cases of intraocular inflammation in patients with neovascular age-related macular degeneration (nAMD) who take AbbVie's investigational drug abicipar pegol develop during the first year of treatment, according to a new report of two-year efficacy and safety results from a couple of pivotal trials.

Meanwhile, the efficacy demonstrated after one year of treatment (https://bit.ly/2VHCGdw) was maintained, Dr. Rahul N. Khurana of Northern California Retina Vitreous Associates, in Mountain View, and colleagues report in Ophthalmology.

Abicipar pegol, originally developed by Allergan, is an anti-VEGF drug with a longer duration of action than currently available agents, allowing it to be injected less frequently. The drug was supposed to be a growth driver for AbbVie when it acquired Allergan in May 2020.

But just a month later, the company announced that the U.S. Food and Drug Administration (FDA) had declined to approve abicipar pegol for nAMD, citing an unfavorable risk-benefit ratio (https://bit.ly/36Mr53c). Allergan then withdrew its application for marketing authorization in the EU, where it was also facing skeptic regulators (https://bit.ly/2ImLfaS).

"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," AbbVie's Dr. Michael R. Robinson said in a press release at the time. "We are committed to working with the FDA to determine the appropriate next steps for Abicipar pegol."

The new analysis pools results from CEDAR and SEQUOIA, two multicenter, randomized, phase-3 clinical trials with identical protocols. The studies enrolled a combined 1,888 nAMD patients (one eye/patient) with best-corrected visual acuity (BCVA) of 24-73 Early Treatment Diabetic Retinopathy Study letters.

Patients received either abicipar 2 mg every eight weeks after three initial doses at baseline and weeks 4 and 8 (abicipar Q8, n=630), abicipar 2 mg every 12 weeks after three initial doses at baseline and weeks 4 and 12 (abicipar Q12, n=628), or ranibizumab 0.5 mg every four weeks (ranibizumab Q4, n=630); 71%, 71% and 83%, respectively, completed 104 weeks of treatment.

Nine percent of patients receiving abicipar left the study due to ocular adverse events (AEs), mostly intraocular inflammation (IOI), during the first year, compared to less than 1% of patients receiving ranibizumab. This accounted for the difference among groups in completion rates.

During the second year, 3% of the abicipar patients who had completed the first year discontinued due to ocular AEs, versus 1% of patients receiving ranibizumab.

The overall incidence of IOI was 15.4%, 15.3% and 0.3% from baseline through week 52 in the abicipar Q8, abicipar Q12 and ranibizumab Q4 groups, respectively, and 16.2%, 17.6% and 1.3% from baseline through week 104. Uveitis, vitritis and iridocyclitis were the most common IOI AEs.

Severe vision loss, defined as a loss of at least 30 letters in BCVA from baseline, at the last visit occurred in a higher proportion of patients in the abicipar Q8 and Q12 groups (5.3% and 5.9%) than in the ranibizumab Q4 group (1.1%) due to the occurrence of IOI and endophthalmitis in the abicipar groups.

Still, the researchers write, "the incidence of IOI AEs from week 52 to week 104 in patients without an IOI AE during the first 52 weeks was not notably different among treatment groups (0.8%, 2.3%, and 1.0% in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively)."

The efficacy of abicipar was maintained throughout treatment in completers. At week 104, 93.0% of completers in the abicipar Q8 group had stable vision (<15-letter loss in BCVA from baseline), compared to 89.8% in the abicipar Q12 group and 94.4% in the ranibizumab Q4 group.

Mean change in BCVA from baseline was +7.8, +6.1 and +8.5 letters, respectively, and mean change in central retinal thickness was -147 um, -146 um and -142 um.

Dr. Khurana and colleagues conclude, "for patients who completed the CEDAR/SEQUOIA study, visual and anatomic changes occurring in the first year of abicipar treatment were maintained in the second year. The increased risk of IOI AEs with abicipar seen in the first year of the study was not sustained, and the incidence of IOI in patients with no previous IOI was low and comparable across treatment groups after week 52."

Allergan sponsored the trials and participated in all aspects of the research, including preparation and approval of the new report.

SOURCE: https://bit.ly/3gfy1Ji Ophthalmology, online November 19, 2020.