Novel Drug Delivery System for the Management of Wet AMD - Episode 3

Treat and Extend Approach to Anti-VEGF Therapy for AMD

May 24, 2021
Carl Regillo, MD, Thomas Jefferson University School of Medicine

,
Diana Do, MD, Stanford University School of Medicine

An overview of standard anti-VEGF treatments for wet AMD and recommendations for individualizing patient therapy with a treat and extend approach.

Carl Regillo, MD: That’s the perfect segue into the next question, which is about treatment. A patient is in your office, suspected of having wet AMD [age-related macular degeneration]. You’ve done your examination, you’ve done your diagnostic testing, and you’ve confirmed patient does have new-onset wet AMD. Obviously treatment needs to be initiated. The standard of care, first-line treatment, is anti-VEGF therapy. It’s intravitreally administered biologics that block freely diffusible VEGF-A, which is thought to be the family of VEGF that’s primarily responsible for that angiogenic trigger and the growth and development of neovascularization. So we’re going to start anti-VEGF therapy. How do you take it from here?

Diana Do, MD: I agree, Carl. Clearly, intravitreal VEGF inhibitors, which are administered in the clinic, are the first-line treatment for wet age-related macular degeneration. There are 4 medicines available in clinical use. Three of these agents are FDA approved: ranibizumab, aflibercept, and brolucizumab. One agent, bevacizumab, is used off-label. Fortunately, there’s a robust body of scientific evidence that suggests all these medicines are very efficacious when dosed appropriately for the treatment of wet macular degeneration. 

There are different treatment strategies, however, that retina specialists can employ when administering these medicines. These VEGF inhibitors can be administered on a fixed-dosing regimen. They also be administered as needed when disease activity is evaluated and caught. Or they can be given on a treat-and-extend regimen, where patients are treated at each visit. If there’s no disease activity, the next evaluation and treatment is extended. I generally recommend a treat-and-extend regimen for most of my patients with wet AMD because evidence has shown that this regimen is quite effective and noninferior to fixed dosing. In addition, treat-and-extend regimens can allow for fewer injections over time and decrease the treatment burden for patients. How about you, Carl? Which regimen do you employ?

Carl Regillo, MD: I am in the norm, because surveys from the American Society of Retina Specialists show that the vast majority of US retina specialists use this treat-and-extend algorithm or approach to utilizing anti-VEGF agents to treat neovascular AMD. We use these drugs to treat other conditions too, like DME [diabetic macular edema]. They’re not necessarily used in the same way. But I agree, the treat-and-extend approach is probably the best balance of trying to avoid undertreatment and trying to avoid overtreatment. In the clinical trials or the prospective studies that tested these drugs in the setting of wet AMD, they were typically in a fixed, frequent regimen. Everyone got ranibizumab, for example, in the ranibizumab phase 3 studies, monthly injections for 1 to 2 years with a 1-year primary end point in the clinical trial. With aflibercept, that was also monthly at first, then every other month or monthly in that clinical trial. 

There was no individualizing the therapy to the patient. We knew from the beginning that not every patient needs monthly or even every-other-month injections to keep the disease in check, to control the signs of exudation and get the best visual outcomes over time. Early on, the as-needed or the treat-and-extend approach is really individualizing therapy for the given patient to determine exactly what their need is to keep the exudation in check. We inject these medicines monthly for the first 2, 3, 4 months. That’s what it takes, on average, to get the macula dried up or close to it. Thereafter, it’s really maintaining the macula in an optimally dry state. That lets us maintain those vision gains that we get early on. We get the vision gains early in the course—the first 2, 3, 4 monthly injections—and then we slowly spread the treatments out per patient to determine exactly what that patient’s needs are.

We find that each patient tends to have a specific disease-free interval with a given medicine. Let’s say ranibizumab in 1 patient might be given every 6 weeks, and that keeps their macula in good shape. For another patient, it could be every 10 or 12 weeks, so that range is anywhere from 4 to 12 weeks in the maintenance phase of therapy. What is the average durability? We’ve been talking about administering these drugs pretty frequently, and you mentioned the word burden. You’re right; it’s a burden to come to the office and get these injections, which are well tolerated but not pleasant. Patients get anxious, and they certainly welcome the notion of coming as infrequently as possible to keep their vision good. So we try to do that. As I tell patients, I’ll try to get your best vision results with the least amount of treatments. But we’re still going to be relatively frequent with the office visits and treatment. What’s the average durability, efficacy, and safety of our drugs?

Diana Do, MD: That’s an important topic. All these drugs, although they’re very efficacious when dosed appropriately, have different durability because half-life and pharmacokinetics of drugs vary slightly. Certainly with some of the FDA-approved medicines, such as aflibercept, in those patients where I administer that medicine, I’m sometimes able to extend those patients to every 3 months between treatments after I have their disease activity under control. We know that if you treat appropriately, you can still maintain the visual acuity benefits if you’re very careful and don’t allow disease to recur.

This speaks to the fact that there’s still an unmet need to develop better medicines that have longer durations of VEGF suppression. The more you make the disease quiescent, the better the chance for visual acuity gain and maintenance over time. That’s why there’s an unmet need to develop medicines, to decrease the burden of frequent office visits and injections. 

Carl, in clinical practice, lots of retrospective studies have shown that patients in real clinics often are undertreated. That is, the average number of injections for wet macular degeneration over the first year may be only 5. Compared with clinical trials, where many patients receive many more injections, 8 or 9 or even 12 injections a year, 5 may not be sufficient for most patients. The culprit is to avoid undertreatment, to treat appropriately, and to personalize the treatment for our patients.

Carl Regillo, MD: Thank you for watching this HCPLive® Peers & Perspectives®. If you enjoyed the content, please subscribe to our e-newsletter to receive upcoming Peers & Perspectives® and other great content right in your in-box.

Transcript Edited for Clarity

x