Quarterly dosing may become reality for wet AMD

Evolutions in technology also may shift the treatment paradigm from monthly to quarterly dosing.

New anti-VEGF agents paired with upcoming drug delivery systems and monitoring technologies may lead to possible quarterly dosing regimens for patients with neovascular age-related macular degeneration.

Reducing the frequency of treatments and increasing the compliance of patients while maintaining good visual outcomes are the goals of wet AMD treatment.

“The biggest driver for long-term visual outcomes is continual dosing and continual treatment. Can we get to that point where we get to quarterly dosing? It’s an optimal way in the future to treat patients with the condition,” Rishi P. Singh, MD, told Ocular Surgery News.

Singh discussed the potential roads for successful quarterly dosing regimens in a presentation at Retina 2019.

Quarterly dosing is possible with the currently available anti-VEGF agents but can only be achieved later in treatment and with intense observation. The results of several studies bear out these conclusions, Singh said. For instance, patients with neovascular AMD in the VIEW 1 and VIEW 2 clinical studies were treated with either intravitreal Eylea (aflibercept, Regeneron) 2 mg every 4 weeks (2q4) or every 8 weeks (2q8) following three initial monthly injections or Lucentis (ranibizumab, Genentech) 0.5 mg every 4 weeks.

Within the second year, 42.5% of patients in the ranibizumab group, 53.9% in the 2q4 group and 47.9% in the 2q8 group were able to transition to a quarterly dosing regimen through week 96. The quarterly dosing patients experienced similar change in best corrected visual acuity compared with patients who received more frequent injections.

Patients who successfully transitioned to quarterly dosing exhibited no retinal fluid on their OCT scans or leakage on their fluorescein angiography at week 52, Singh said.

“Those were the patients whose treatment could be extended in the second year,” he said.

New anti-VEGF agents could allow patients to be dosed quarterly at the start of treatment instead of a year into therapy. Patients treated with abicipar (Allergan) and brolucizumab (Novartis) in certain clinical trials experienced varying degrees of quarterly dosing success, Singh said.

The HAWK and HARRIER studies were designed to evaluate quarterly dosing of brolucizumab in neovascular AMD patients. After the loading phase, more than 50% of patients who received brolucizu­mab 6 mg were successfully maintained on quarterly dosing through week 48.

After the first year of the CEDAR and SEQUOIA studies, patients who had received either six or eight injections of abicipar, a DARPin molecule, demonstrated similar efficacy in treating neovascular AMD as patients who received 13 injections of ranibizumab.

Patients in the study were fully committed to their dosing regimen and were not given the option to move to a more frequent dosing group, Singh said.

Advancements in delivery and monitoring systems may make quarterly dosing easier to achieve. In the LADDER study, participants were implanted with the Port Delivery System (Genentech/Roche), a permanent, refillable intraocular implant that allows continuous delivery of ranibizumab into the vitreous.

The study ended at 21 months, but patients likely would not have needed a refill of ranibizumab until 24 months, Singh said.

“It has yet to be determined what the final phase of the study will look like with regard to what concentration they used, but there is encouraging data that says quarterly dosing is definitely possible, if not more so, with this implant device,” he said.

In the offing is the ability to perform at-home scans with Notal Vision’s OCT system. The device received breakthrough device designation from the FDA and will be coupled with an artificial intelligence system to read fluid levels on each scan, Singh said.

The home OCT system will identify patients who are transitioning from non-exudative AMD to exudative AMD and will automatically send “wet” reads to the patient’s ophthalmologist for evaluation.

“It is very beneficial. We can learn what the real track of fluid is rather than what we think the track of fluid is over time,” Singh said. – by Robert Linnehan

Disclosure: Singh reports he is a consultant for Bausch + Lomb, Genentech, Novartis, Optos, Regeneron and Zeiss and does sponsored research with Apellis.

New anti-VEGF agents paired with upcoming drug delivery systems and monitoring technologies may lead to possible quarterly dosing regimens for patients with neovascular age-related macular degeneration.

Reducing the frequency of treatments and increasing the compliance of patients while maintaining good visual outcomes are the goals of wet AMD treatment.

“The biggest driver for long-term visual outcomes is continual dosing and continual treatment. Can we get to that point where we get to quarterly dosing? It’s an optimal way in the future to treat patients with the condition,” Rishi P. Singh, MD, told Ocular Surgery News.

Singh discussed the potential roads for successful quarterly dosing regimens in a presentation at Retina 2019.

Quarterly dosing is possible with the currently available anti-VEGF agents but can only be achieved later in treatment and with intense observation. The results of several studies bear out these conclusions, Singh said. For instance, patients with neovascular AMD in the VIEW 1 and VIEW 2 clinical studies were treated with either intravitreal Eylea (aflibercept, Regeneron) 2 mg every 4 weeks (2q4) or every 8 weeks (2q8) following three initial monthly injections or Lucentis (ranibizumab, Genentech) 0.5 mg every 4 weeks.

Within the second year, 42.5% of patients in the ranibizumab group, 53.9% in the 2q4 group and 47.9% in the 2q8 group were able to transition to a quarterly dosing regimen through week 96. The quarterly dosing patients experienced similar change in best corrected visual acuity compared with patients who received more frequent injections.

Patients who successfully transitioned to quarterly dosing exhibited no retinal fluid on their OCT scans or leakage on their fluorescein angiography at week 52, Singh said.

“Those were the patients whose treatment could be extended in the second year,” he said.

New anti-VEGF agents could allow patients to be dosed quarterly at the start of treatment instead of a year into therapy. Patients treated with abicipar (Allergan) and brolucizumab (Novartis) in certain clinical trials experienced varying degrees of quarterly dosing success, Singh said.

The HAWK and HARRIER studies were designed to evaluate quarterly dosing of brolucizumab in neovascular AMD patients. After the loading phase, more than 50% of patients who received brolucizu­mab 6 mg were successfully maintained on quarterly dosing through week 48.

After the first year of the CEDAR and SEQUOIA studies, patients who had received either six or eight injections of abicipar, a DARPin molecule, demonstrated similar efficacy in treating neovascular AMD as patients who received 13 injections of ranibizumab.

Patients in the study were fully committed to their dosing regimen and were not given the option to move to a more frequent dosing group, Singh said.

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Advancements in delivery and monitoring systems may make quarterly dosing easier to achieve. In the LADDER study, participants were implanted with the Port Delivery System (Genentech/Roche), a permanent, refillable intraocular implant that allows continuous delivery of ranibizumab into the vitreous.

The study ended at 21 months, but patients likely would not have needed a refill of ranibizumab until 24 months, Singh said.

“It has yet to be determined what the final phase of the study will look like with regard to what concentration they used, but there is encouraging data that says quarterly dosing is definitely possible, if not more so, with this implant device,” he said.

In the offing is the ability to perform at-home scans with Notal Vision’s OCT system. The device received breakthrough device designation from the FDA and will be coupled with an artificial intelligence system to read fluid levels on each scan, Singh said.

The home OCT system will identify patients who are transitioning from non-exudative AMD to exudative AMD and will automatically send “wet” reads to the patient’s ophthalmologist for evaluation.

“It is very beneficial. We can learn what the real track of fluid is rather than what we think the track of fluid is over time,” Singh said. – by Robert Linnehan

Disclosure: Singh reports he is a consultant for Bausch + Lomb, Genentech, Novartis, Optos, Regeneron and Zeiss and does sponsored research with Apellis.