Genentech’s Port Delivery System retinal implant delivers ranibizumab for more than 6 months.

Anti-VEGF injections have completely changed the paradigm for treating retinal disease. For neovascular or wet AMD, it offered the first treatment that predictably improved vision. However, that treatment response oftentimes requires injections as often as once a month — for the rest of a patient’s life.

Genentech’s Port Delivery System with ranibizumab (PDS) represents the next generation of therapy. It offers the possibility of continuous anti-VEGF therapy with an outpatient surgical procedure and refills twice annually in the office. “This is a very exciting development,” says W. Lloyd Clark, MD, a retina specialist at Palmetto Retina Center in West Columbia, S.C., who was a clinical trial investigator of the product in the Archway Study.^1-3 “Of the 248 wet AMD patients being treated with PDS, 98.4% were able to go 6 months without needing additional treatment.”

Nancy Holekamp, MD, director of retina services at the Center for Macular Degeneration at the Pepose Vision Institute in Chesterfield, Mo., was another investigator in the Archway Study. “Before PDS was developed, going 6 months without treatment and maintaining vision was just not possible for patients. It’s truly a game-changer.”

HOW IT WORKS

PDS is a permanent refillable eye implant, approximately the size of a grain of rice, that is inserted during a minimally invasive, one-time outpatient surgery. It continuously delivers a customized formulation of ranibizumab into the eye over time and is refilled every 6 months, says Anne Fung, MD, global development lead for PDS Platform Surgery & Device at Genentech, in South San Francisco, Calif.

“By maintaining therapeutic drug concentration levels of ranibizumab with two refills per year, PDS may offer greater outcomes certainty in terms of vision gains and maintaining those gains for people living with retinal diseases, including wet AMD,” Dr. Fung says. “Additionally, by decreasing the need for frequent injections, PDS may reduce the burden of treatment associated with standard anti-VEGF treatments.”

If FDA approved, PDS would be the first and only eye implant with continuous drug delivery that offers people with wet AMD an alternative to frequent eye injections of anti-VEGFs, the current standard of care.

CLINICAL APPLICATIONS

According to Dr. Clark, the best wet AMD candidates for the PDS are patients who have demonstrated a biologic response to ranibizumab injections and appear to need chronic therapy.

For patients who have difficulty maintaining regular appointments for injections, the PDS can be a great alternative. “But it does involve a surgical procedure, so patient selection is an important factor,” Dr. Fung says.

In a Patient Preference Questionnaire⁴ surveying all PDS patients in the Archway Trial, 93% said they preferred PDS over intravitreal injections. “The ability to receive fewer treatments was a key reason for this preference, along with less discomfort and less worry or nervousness about injections,” Dr. Holekamp says.

Most of Dr. Holekamp’s patients who had an implant in one eye but received injections in their other eye in the clinical trial for wet AMD can’t wait for the PDS to be approved so they can have an implant in each eye, she says.

WHY RANIBIZUMAB?

In pivotal clinical trials^5,6 conducted more than 15 years ago, ranibizumab injections given on a monthly basis demonstrated visual acuity improvements in individuals with wet AMD that have not since been improved upon. Since then, ranibizumab has been validated with a wealth of positive clinical trial data^7,8 demonstrating efficacy and safety in the real-world setting. “It remains the gold standard,” Dr. Holekamp says.

Ranibizumab also has unique structural properties that allow for the special formulation that enables continuous delivery. “Thus, it’s an optimal choice for delivery with PDS and has been formulated specifically for continuous delivery via the implant,” Dr. Fung says.

The continuous delivery of ranibizumab can also reduce the peaks and troughs in BCVA that can occur with monthly injections.^9,10 Patients can maintain a steady BCVA over a longer time period.¹¹

APPROACHING FDA APPROVAL

The Portal long-term extension study,¹² currently ongoing, is investigating the long-term safety and tolerability of PDS for the treatment of wet AMD, with data expected later this year.

PDS is also being studied in the Phase 3 Pagoda trial¹³ for treating diabetic macular edema, a vision-threatening complication of diabetes, and the Phase 3 Pavilion trial¹⁴ for treating diabetic retinopathy without diabetic macular edema. OM

REFERENCES

1. Campochiaro P. Primary analysis results of the Phase 3 Archway trial of the port delivery system with ranibizumab for patients with neovascular AMD. American Society of Retina Specialists Annual Meeting 2020; Seattle; July 24-28.
2. Regillo C. Port delivery system with ranibizumab (PDS) for nAMD: Updated data from the Archway phase 3 trial. Angiogenesis, Exudation, and Degeneration 2021 Annual Meeting; 2021. Feb. 12-13.
3. A phase III study to evaluate the port delivery system with ranibizumab compared with monthly ranibizumab injections in participants with wet age-related macular degeneration (ARCHWAY). ClinicalTrials.gov . https://clinicaltrials.gov/ct2/show/NCT03677934 . Accessed Sept. 27, 2021.
4. Holekamp N, on behalf of Archway investigators. Primary analysis results of the phase 3 Archway Trial of the port delivery system with ranibizumab for patients with neovascular AMD. American Academy of Ophthalmology Annual Meeting; 2020 Nov. 13-15.
5. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355:1419-1431.
6. Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology. 2009 Jan;116:57-65.e5. doi: 10.1016/j.ophtha.2008.10.018.
7. Silva R, Axer-Siegel R, Eldem B, Guymer R, Kirchhof B, Papp A, et al. The SECURE study: long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration. Ophthalmology. 2013 Jan;120:130-9. doi: 10.1016/j.ophtha.2012.07.026. Epub 2012 Sep 25.
8. Holz FG, Figueroa MS, Bandello F, Yang Y, Ohji M, Dai H, et al. Ranibizumab treatment in treatment-naive neovascular age-related macular degeneration: results from LUMINOUS, a global real-world study. Retina. 2020 Sep;40:1673-1685.
9. Xu L, Lu T, Tuomi L, Jumbe N, et al. Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: a population approach. Invest Ophthalmol Vis Sci. 2013 Mar 5;54:1616-1624. doi: 10.1167/iovs.12-10260. https://pubmed.ncbi.nlm.nih.gov/23361508/ . Accessed Sept. 28, 2021.
10. Muether PS, Hermann MM, Viebahn U. et al. Vascular endothelial growth factor in patients with exudative age-related macular degeneration treated with ranibizumab. Ophthalmology. 2012 Oct;119:2082-2086. doi: 10.1016/j.ophtha.2012.07.041. Epub 2012 Aug 22. https://pubmed.ncbi.nlm.nih.gov/22920670/ . Accessed Sept. 28, 2021.
11. Regillo C, et al. FDA accepts application for Roche’s Port Delivery System with ranibizumab (PDS) for treatment of neovascular or “wet” age-related macular degeneration (nAMD). Presented at the Bascom Palmer Eye Institute Angiogenesis, Exudation, and Degeneration Meeting 2021. https://www.roche.com/media/releases/med-cor-2021-06-24.htm . Accessed Sept. 28, 2021.
12. Extension study for the port delivery system with ranibizumab (portal). ClinicalTrials.gov . https://clinicaltrials.gov/ct2/show/NCT03683251 . Accessed Sept. 28, 2021.
13. This study will evaluate the efficacy, safety, and pharmacokinetics of the port delivery system with ranibizumab in participants with diabetic macular edema compared with intravitreal ranibizumab (Pagoda). ClinicalTrials.gov . https://clinicaltrials.gov/ct2/show/NCT04108156 . Accesseed Sept. 28, 2021.
14. A multicenter, randomized study in participants with diabetic retinopathy without center-involved diabetic macular edema to evaluate the efficacy, safety, and pharmacokinetics of ranibizumab delivered via the port delivery system relative to the comparator arm (PAVILION). ClinicalTrials.gov . https://clinicaltrials.gov/ct2/show/NCT04503551 . Accessed Sept. 27, 2021.