Results for aflibercept 8 mg from pivotal PHOTON trial show vision gains at extended dosing intervals in DME

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Regeneron Pharmaceuticals Inc. announced top-line, two-year (96 weeks) data for aflibercept 8 mg from the pivotal PHOTON trial in patients with diabetic macular edema (DME).

The data comes on the heels of news the FDA issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) for aflibercept 8mg for the treatment of patients with wet age-related macular degeneration (wAMD), DME and diabetic retinopathy (DR), solely due to an ongoing review of inspection findings at a third-party filler.

In a separate statement, Regeneron indicated the FDA did not identify any issues with the aflibercept 8mg clinical efficacy or safety, trial design, labeling or drug substance manufacturing in the CRL, and it did n ot request additional clinical data or trials. The company also pledged to work with the FDA and third-party filer to bring aflibercept 8 mg to patients with wAMD, DME and DR as soon as possible.

In the 2-year data from the PHOTON trial, Regeneron noted in its news release that aflibercept 8 mg patients were initially randomly assigned to either 12- or 16-week dosing intervals (after 3 initial monthly doses) and were able to shorten or extend dosing intervals if pre-specified criteria were met. The longer-term data among aflibercept 8 mg patients who completed the trial demonstrated that the vast majority of patients were able to maintain or further extend these dosing intervals through two years with:

• 89% maintaining ≥12-week dosing intervals through two years, compared to 93% through one year (48 weeks)
  
  
• 83% maintaining ≥16-week dosing intervals through two years, compared to 89% maintaining a 16-week dosing interval through one year
  
  
• 43% meeting the criteria for ≥20-week dosing intervals by week 96, including 16% and 27% who were eligible for 20- and 24-week dosing intervals, respectively
  
  

“The two-year PHOTON results for aflibercept 8 mg in patients with diabetic macular edema are extremely compelling,” Jeffrey Heier, MD, director of the Retina Service and Retina Research at Ophthalmic Consultants of Boston and a trial investigator, said in the news release. “To be able to rapidly achieve extended dosing intervals without any sacrifice of vision gains over two years is a tremendous benefit in the treatment of diabetic macular edema.”

Moreover, David M. Brown, MD, FACS, director of Research at Retina Consultants of Texas and a trial investigator, pointed out the 2-year PHOTON results surpassed his expectations and indicate that the majority of patients may eventually be able to control their diabetic macular edema with as few as 2 or 3 aflibercept 8 mg injections per year, if approved by regulatory authorities, with similar excellent visual gains and a safety profile consistent with aflibercept given every 8 weeks.

“Reducing the treatment burden in patients with diabetic macular edema is a critical unmet need, and the two-year PHOTON results reinforce the potential of aflibercept 8 mg to become the standard of care for the treatment of diabetic macular edema.”

The company noted in its news release PHOTON (N = 658) is a double-masked, active-controlled pivotal trial evaluating non-inferiority of aflibercept 8 mg 12-week (n = 328) and 16-week (n = 163) dosing regimens after three initial monthly doses compared to an 8-week dosing regimen for aflibercept Injection (n = 167) after five initial monthly doses. In addition to the vast majority of trial patients maintaining extended dosing intervals through two years, visual gains for aflibercept 8 mg remained consistent with the first year of the trial.

According to the news release, in PHOTON, the safety of aflibercept 8 mg also continued to be similar to aflibercept through two years and remained consistent with the known safety profile of aflibercept from previous clinical trials for DME. Ocular treatment emergent adverse events (TEAE) occurring in ≥5% of patients in any treatment group, in decreasing frequency, were cataract, vitreous floaters, and conjunctival hemorrhage.

There were no cases of retinal vasculitis, occlusive retinitis or endophthalmitis. The rate of intraocular inflammation was 1.2% for both the aflibercept and aflibercept 8 mg groups. Anti-platelet trialists' collaboration-defined arterial thromboembolic TEAEs occurred in 7.2% of patients treated with aflibercept and 6.5% of patients treated with aflibercept 8 mg.

“The aflibercept 8 mg clinical trial program is the first to demonstrate that patients with diabetic macular edema can immediately be treated with every 12- or 16-week dosing after their initial monthly doses and experience lasting vision control,” George D. Yancopoulos, MD, PhD, board co-chair, president and chief scientific officer at Regeneron, and a principal inventor of EYLEA, said in the news release. “With these two-year results, Regeneron continues to raise the bar in clinical advancements for retinal treatments and remains committed to pursuing groundbreaking innovations in ophthalmology.”

The two-year data from the pivotal PULSAR trial for aflibercept 8 mg in wet age-related macular degeneration are expected in the third quarter of 2023, and the two-year data from both PHOTON and PULSAR are planned for presentation at an upcoming medical meeting.

Aflibercept 8 mg is investigational, and its safety and efficacy have not been fully evaluated by any regulatory authority. Aflibercept 8 mg is being jointly developed by Regeneron and Bayer AG, with Regeneron sponsoring the PHOTON trial. In the U.S., Regeneron maintains exclusive rights to EYLEA and aflibercept 8 mg. Bayer has licensed the exclusive marketing rights outside of the U.S., where the companies share equally the profits from sales of EYLEA and aflibercept 8 mg following any regulatory approvals.

About the Aflibercept 8 mg Clinical Trial Program

PULSAR in wAMD and PHOTON in DME are double-masked, active-controlled pivotal trials that are being conducted in multiple centers globally. In both trials, patients were randomly assigned into 3 treatment groups to receive either: aflibercept 8 mg every 12 weeks, aflibercept 8 mg every 16 weeks, or EYLEA every 8 weeks. The lead sponsors of the trials were Bayer for PULSAR and Regeneron for PHOTON.

Patients treated with aflibercept 8 mg in both trials had 3 initial monthly doses, and patients treated with aflibercept received 3 initial doses in PULSAR and 5 in PHOTON. In the first year, patients in the aflibercept 8 mg groups could have their dosing intervals shortened down to an every 8-week interval if protocol-defined criteria for disease progression were observed. Intervals could not be extended until the second year of the study. Patients in all EYLEA groups maintained a fixed 8-week dosing regimen throughout their participation in the trials.

About DME

DME is a common complication in eyes of people living with diabetes. DME occurs when high levels of blood sugar lead to damaged blood vessels in the eye that leak fluid into the macula. This can lead to vision loss and, in some cases, blindness. Of the nearly 28 million American adults living with diabetes, an estimated 1.2 million have DME.