Higher molar dose in the real world and clinical trials

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The golden age of retina care may be upon us. Patients with age-related macular degeneration (AMD), diabetic macular edema (DME), and associated conditions may be candidates for a full slate of next-generation therapeutics. In a
series of podcasts from Ophthalmology Times Europe® and Modern Retina, John Kitchens, MD, sat down with fellow retina specialists to discuss dosing patients with durability of results in mind. All 3 conversations centered around new therapies targeting retinal disease, with a focus on faricimab and aflibercept 8 mg.

Episode 1

Higher molar dose and its translation into clinical practice

In episode 1, Kitchens was joined by Peter Kaiser, MD, to discuss higher molar dose and translating this approach into clinical practice. They discussed common challenges clinicians may face in treating patients with higher molar doses, shared clinical pearls for helping patients transition to a higher dose, and identified potential biomarkers that indicate a need for frequent anti-VEGF injections in patients with wet AMD.

Kitchens and Kaiser took a “deep dive” into the philosophy behind increasing the dose of aflibercept and the potential for improved drug durability in the eye. As they discussed, modeling suggests slower ocular clearance with a higher dose of aflibercept. Together, they addressed strategies for determining drug half-life and appropriate dosing for anti-VEGF treatments. Using aflibercept as an example, Kitchens and Kaiser explained how the half-life of aflibercept is determined in the eye using pharmacokinetic sampling and modeling.

Other highlights included dose regimen modifications and durability of the drug in second-year studies and approaches to accelerating aflibercept dosing intervals for patients with wet AMD. Clinical trial design was also on the docket, concluding the conversation with methods of translating the “treat and extend” approach to the real world.

Episode 2:

PULSAR study findings: Implications for treating nAMD in clinical practice

Next, Kitchens was joined by David Brown, MD, to discuss the PULSAR study results and their relation to patients with neovascular AMD in clinical practice. They highlighted developments in ocular drug delivery, including new formulations of existing drugs and potential clinical challenges, focusing on results from the phase 3 PULSAR clinical trial (NCT04423718).

Brown explained the variability in patient clearance rates, their impact on treatment outcomes, and clinical practice findings specific to aflibercept dosing. He advocated prioritizing an individualized approach based on the patient’s response and disease activity.

They also gave an overview of safety and efficacy findings for retinal disease therapies. Discussion points included extending drug treatment from 8 weeks and onward with positive patient response, as well as the potential for future label changes with regulatory agencies.

Finally, Brown emphasized the limitations and opportunities unique to ocular therapeutic manufacturing processes. In particular, he and Brown focused on the challenges of creating fully human antibodies to VEGF.

EPISODE 3

PHOTON results and their relation to DME patients in your practice

In the final episode of the series, Kitchens was joined by Diana Do, MD, to discuss the results of the phase 2/3 PHOTON trial (NCT04429503) and their relation to patients with DME in clinical practice. They explored the potential for more frequent dosing of aflibercept for DME, focusing on safety monitoring and adjuvant steroids.

Highlighting the variability in the intraocular half-life of aflibercept, Do and Kitchens considered how factors such as patient characteristics and vitreous liquefaction may have an impact. They also touched upon a common concern among retina specialists: the concept of nonresponders. They discussed why frequent dosing may indicate a need for more frequent treatment rather than a lack of response to the drug.

Much of the conversation centered around the needs of patients with DME and response variability among that patient group. They addressed whether 8 mg of aflibercept every 12 to 16 weeks is noninferior to 2 mg every 8 weeks in patients with DME.

Do advocated for using the art of medicine to tailor aflibercept dosing based on patient response. In some cases, she and Kitchens pointed out that mixing steroids with aflibercept may help treat recalcitrant DME, and using combination therapy shows improved response in DME treatment. They also provided a convenient list of safety signals for hypertension, intraocular inflammation, and retinal vasculitis, all crucial information for clinicians using aflibercept 8 mg in their practices. •