The letter makes reference to an ongoing review of inspection findings from a third-party filler involved with the drug development. Regeneron will not require additional trial data.
The US Food and Drug Administration (FDA) has filed a Complete Response Letter (CRL) to Regeneron in response to the company's biologics license application (BLA) for aflibercept 8 mg, as a treatment of patients with wet age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy (DR).1
According to a Regeneron statement released Tuesday, the CRL pertained "solely" due to an ongoing review of findings from a third-party filler inspection.
"The CRL did not identify any issues with the aflibercept 8 mg clinical efficacy or safety, trial design, labeling or drug substance manufacturing, and no additional clinical data or trials have been requested," the company stated. "Regeneron is committed to working closely with the FDA and the third-party filler to bring aflibercept 8 mg to patients with wAMD, DME and DR as quickly as possible."
The application was supported by positive data from the PULSAR trial for wet AMD and the PHOTON trial for DME. Both trials reported those treated with aflibercept 8 mg in PULSAR (n = 673) and PHOTON (n = 491) met the primary endpoint of noninferiority in vision gains for both 12- and 16-week dosing regimens at 48 weeks, compared to patients treated with an aflibercept 8-week dosing regimen (PULSAR, n = 336; PHOTON, n = 167).2,3
The analyses showed the majority of patients randomized to aflibercept 8 mg in both trials maintained 12- and 16-week dosing regimens to which they were respectively initiated through 38 weeks (wet AMD, 79% and 77%; DME, 91% and 89%).
Safety profiles were similar between aflibercept 8 mg and aflibercept in both trials and remained consistent with the known safety profile reported in previous clinical trials. The safety analysis showed ocular adverse events occurred in 31% of patients treated with aflibercept 8mg versus 28% of those treated with aflibercept in PHOTON, and 38% versus 39% in PULSAR. No cases of retinal vasculitis, occlusive retinitis, or endophthalmitis were reported in either trial.
At the 2023 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, experts shared their thoughts on the potential approval of aflibercept 8 mg and where it may fit into the treatment toolbox.
“I think these data sets [PULSAR and PHOTON], which are large and extensive in global clinical trials, show that there is a promise that 8 mg aflibercept will be a useful treatment option for patients, once it’s available,” Diana V. Do, MD, Byers Eye Institute, Stanford University told HCPLive.
“It could be a total replacement,” David Brown, MD, Retina Consultants of Texas told HCPLive regarding a potential FDA approval. “We’ve had over 70 million doses of 2 mg and most physicians around the world are very comfortable with the safety profile. It looks like we have a similar safety profile with this formulation. So, I don’t see a reason why physicians wouldn’t implement it as a replacement in starting new patients.”4