Spotlight ON TECHNOLOGY & TECHNIQUE

Eylea Outcomes Support Extended Intervals

By Robert Murphy, Contributing Editor

Retina specialists have eagerly awaited the introduction of a third anti-VEGF agent to join Lucentis and Avastin in the pharmacological battle against AMD, and late last year their wish was granted with the November 2011 approval of Eylea (aflibercept, Regeneron Pharmaceuticals) to treat wet age-related macular degeneration.

Eylea's recommended dosing of a 2 mg intravitreal injection monthly for the first three months followed by the same injection every two months allows clinicians to individualize AMD treatment based on the disease's severity, while potentially setting the stage for reduced numbers of injections and patient visits to the practice over the long term.

Strong Start

What has been the reaction among retina specialists thus far? “In our own experience with Eylea, our patients are doing well,” says K. Bailey Freund, MD, of Vitreous Retina Macula Consultants of New York. “We've used Eylea mainly for patients who have activity in their disease despite monthly Lucentis. Overall, I've been pleased with those patients — the ones who had not been staying completely dry with Lucentis or Avastin,” he says. “They've responded so far to Eylea during the first four or five months of use.”

The new medication's clinical results argue in favor of the AMD treatment approach known as “treat and extend,” first described several years ago by Dr. Freund.

An alternative to the “treat and observe” as-needed basis for anti-VEGF injections, “treat and extend” initially calls for exams and loading-dose injections monthly until the macula is dry and vision has stabilized, then gradually extends the intervals between treatments depending on the presence or lack of neovascular leakage and other criteria, as well the doctor's comfort level and that of the patient.

“It just becomes sort of common sense,” Dr. Freund says. “With experience, you learn that, for many patients, an individualized treatment regimen may be preferable to monthly treatment,” Dr Freund says. “After the patient is stabilized and there is no fluid, bring them back in five or six weeks instead. Each successive visit at which stability is maintained is another opportunity to extend the interval. Depending on your comfort level, you may eventually extend patients out to perhaps eight or more weeks,” Dr. Freund says.

While some extend the interval for Lucentis or Avastin out to 12 weeks, Dr. Freund feels more comfortable with a maximum interim of eight weeks. “I am concerned that eyes may develop recurrent bleeding between injections when the treatment interval is extended past two months,” he says.

Reduce Doses, Not Results

Phase 3 clinical trials involving some 2,400 patients compared Eylea with Lucentis for neovascular AMD and included four treatment arms: (1) monthly 0.5 mg Lucentis injections; (2) monthly 0.5 mg Eylea injections; (3) monthly 2 mg Eylea injections; and (4) 2 mg Eylea injections given monthly for three months and then every two months.

The visual outcomes suggest that Eylea meets the results of either Lucentis or Avastin given monthly. Note that only in the Eylea trial did the protocol indicate extended intervals following three monthly injections. No formal study has yet tested Lucentis or Avastin at intervals of two months or more.

Patients receiving Eylea 2 mg every two months following the initial loading dose experienced average visual acuity gains from baseline of 8.4 letters at week 52 and 7.6 letters at week 96 and received an average of 11.2 injections over two years (including 4.2 the second year). The outcomes for 0.5 mg Lucentis were essentially indistinguishable to these findings. Patients gained, on average, 8.7 letters from baseline at week 52 and 7.9 letters at week 96. Patients given Lucentis received an average of 16.5 injections over two years (with 4.7 in the second year). Dosing frequency reduced most over the first year. Retina specialists will have to monitor patients closely during successive years and calibrate the regimen to each patient's circumstances.

The feeling in these early days is that Eylea delivers on its promise of offering reduced dosing with efficacy comparable to that of monthly Lucentis or Avastin, promoting greater convenience and lower cost. Perhaps in time, a “treat and extend” approach to Eylea might allow the opportunity to reduce dosage frequency to lower levels yet. OM

For more information, visit www.eylea.com.