The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery

Abstract

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system designed for the continuous delivery of ranibizumab into the vitreous for 6 months and beyond. The PDS includes an ocular implant, a customized formulation of ranibizumab, and four dedicated ancillary devices for initial fill, surgical implantation, refill-exchange, and explantation, if clinically indicated. Ranibizumab is an ideal candidate for the PDS on account of its unique physicochemical stability and high solubility. Controlled release is achieved via passive diffusion through the porous release control element, which is tuned to specific drug characteristics to accomplish a therapeutic level of ranibizumab in the vitreous. To characterize drug release from the implant, release rate was measured in vitro with starting concentrations of ranibizumab 10, 40, and 100 mg/mL, with release of ranibizumab 40 and 100 mg/mL found to remain quantifiable after 6 months. Using a starting concentration of 100 mg/mL, active release rate at approximately 6 months was consistent after the initial fill and first, second, and third refills, demonstrating reproducibility between implants and between multiple refill-exchanges of the same implant. A refill-exchange performed with a single 100-µL stroke using the refill needle was shown to replace over 95% of the implant contents with fresh drug. In vitro data support the use of the PDS with fixed refill-exchange intervals of at least 6 months in clinical trials.

Keywords:

• Ranibizumab
• Port Delivery System
• continuous drug delivery
• nAMD
• ocular implant
• retina

Acknowledgments

The authors would like to acknowledge Josh Horvath for discussions and help with aspects of device development.

Author contributions

SVR had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Ranade, Tam, Rea, Horvath, Hieb.

Acquisition, analysis, or interpretation of data: Ranade, Wieland, Tam, Rea, Horvath, Hieb, Jia, Barteselli, Stewart.

Drafting and critical revision of the manuscript for important intellectual content: Ranade, Wieland, Tam, Rea, Horvath, Hieb, Jia, Grace, Barteselli, Stewart.

Supervision: Ranade

Meeting presentation

Parts of these data were presented at the Association for Research in Vision and Ophthalmology Virtual Meeting, May 1–7, 2021; the Controlled Release Society Virtual Annual Meeting, July 25–29, 2021; the American Association of Pharmaceutical Scientists, PharmSci 360, Oct 17–20, 2021; and the American Academy of Ophthalmology Annual Meeting, Nov 12–15, 2021.

Disclosure statement

Dr Ranade, Ms Tam, Dr Rea, Dr Horvath, Dr Hieb, Dr Jia, Ms Grace, and Dr Barteselli reported being employees of Genentech, Inc. Dr Wieland reported financial support from and being a consultant for Genentech, Inc.; and performing research for Genentech, Inc., Kodiak, Norlase, and Regeneron. Dr Stewart reported being a consultant for Genentech, Inc., Merck, Surrozen, and Valitor; and a personal financial interest in Roche.

Additional information

Funding

Genentech, Inc., a member of the Roche Group, provided financial support for the study and participated in the study design; conducting the study; data collection, management, analysis, and interpretation; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. Third-party writing assistance was provided by Dionne Turnbull, PhD, of Envision Pharma Group, funded by Genentech Inc., a member of the Roche Group.