Genentech (Roche) has provided a clear signal that it believes in the future of sustained-release delivery of biologic drugs to treat retinal disease when it acquired ForSight Vision4 in late December. ForSight has been collaborating with Roche’s Genentech division since 2010, when it licensed the exclusive rights to its refillable rigid port delivery system (RPDS) to Genentech as an initial step toward offering Lucentis (ranibizumab) in a sustained-release format.
Currently, the only ophthalmic drugs approved by the US Food and Drug Administration (FDA) for sustained-release delivery have almost exclusively been steroids. They include Ozurdex (Allergan) for uveitis and DME, Iluvien (Alimera Sciences) for DME, and Retisert (Bausch + Lomb) for uveitis.
The RPDS is a durable intravitreal implant that is placed through a scleral incision in a one-time surgical procedure. It is then refilled by a physician using a proprietary refill needle in an office setting. The timing for refills is currently being studied but it is estimated by the company at 4 to 6 months. Currently in a phase 2 clinical trial, it could potentially replace intravitreal injections of Lucentis now normally given every 4 to 6 weeks.
Technology From an Ophthalmic Incubator
Specific terms of the ForSight Vision4 acquisition were not disclosed but included an upfront payment and additional payments for meeting certain clinical and commercial milestones. ForSight Vision4, which is focused on the future development of sustained-release delivery for a range of therapeutic agents, is one of a number of new companies that have come out of the ForSight Labs ophthalmic incubator started by noted innovator Eugene de Juan, Jr., MD.
"In 2005, I witnessed the presentation at the American Society of Retina Specialists meeting of the dramatic visual improvements from monthly injections of Lucentis for choroidal neovascularization associated with AMD, which profoundly changed ophthalmology," said Dr. de Juan in a press release. "The ForSight Vision4 PDS was developed specifically to continue to enhance the treatment of patients with retinal diseases.”
In recent years, Genentech has been moving the sustained-release technology through early-stage clinical trials. Currently, the company is conducting the 220-patient phase 2 LADDER study that, if successful, would bring doctors and patients one step closer to a less burdensome treatment regimen requiring fewer office visits and injections.
Genentech researchers have long believed that ranibizumab could be successful in a sustained-release format, because the drug has the stability to remain effective for months when placed in an implant.1
In the small phase 1 study, the RPDS implant was well tolerated and showed an improvement in visual acuity comparable to monthly Lucentis injections, establishing proof of concept for the system. Genentech’s RPDS implant also has received FDA fast-track designation, which is designed to facilitate development and expedite review of drugs to treat serious conditions and fill an unmet medical need.
“With the investigation of the RPDS implant, we hope to provide patients with the maximum benefits of treatment with Lucentis while reducing the number of office visits and injections they require,” said Jill Hopkins, MD, medical director, Genentech Ophthalmology, in an announcement about the product.
“Inconsistency in treatment adherence can sometimes result in vision loss,” said Richard F. Dreyer, MD, LADDER clinical investigator. “If successful, the RPDS implant could become a useful tool to better manage wet AMD by providing a consistent level of treatment and potentially result in better long-term visual outcomes.”2
"This transaction marks the successful culmination of an early and ongoing collaboration between the ForSight Vision4 team and the team at Genentech, and puts the PDS technology on a path to revolutionize retinal therapies for patients worldwide," said K. Angela Macfarlane, president and CEO of ForSight Vision4, Inc, in a press release. LADDER is an interventional, randomized, double-blind, active comparator multicenter study.
Other Companies Study Sustained-Release Therapies
In a related development, Regeneron has recently begun its own sustained-release initiative for its anti-VEGF drug Eylea (aflibercept), which is currently delivered via regular intravitreal injections. Ocular Therapeutix is now developing proprietary sustained-release hydrogel-based drug delivery depots that can be implanted and formulated with both small- and large-molecule pharmaceuticals, such as tyrosine kinase inhibitors and protein-based anti-VEGFs, respectively, with the goal of delivering sustained and therapeutic levels of drugs to targeted ocular tissues. The formulation for Eylea is in preclinical development.
Alcon and pSivida are also active in developing sustained-release approaches to combat retinal disease. Alcon’s investigational small-molecule, single-chain antibody fragment brolucizumab (RTH258) has been identified as a drug that is particularly suited for use in a sustained-release format. pSivida developed the implant vehicles for both Iluvien and Retisert. RP
References
Currently, the only ophthalmic drugs approved by the US Food and Drug Administration (FDA) for sustained-release delivery have almost exclusively been steroids. They include Ozurdex (Allergan) for uveitis and DME, Iluvien (Alimera Sciences) for DME, and Retisert (Bausch + Lomb) for uveitis.
The RPDS is a durable intravitreal implant that is placed through a scleral incision in a one-time surgical procedure. It is then refilled by a physician using a proprietary refill needle in an office setting. The timing for refills is currently being studied but it is estimated by the company at 4 to 6 months. Currently in a phase 2 clinical trial, it could potentially replace intravitreal injections of Lucentis now normally given every 4 to 6 weeks.
Technology From an Ophthalmic Incubator
Specific terms of the ForSight Vision4 acquisition were not disclosed but included an upfront payment and additional payments for meeting certain clinical and commercial milestones. ForSight Vision4, which is focused on the future development of sustained-release delivery for a range of therapeutic agents, is one of a number of new companies that have come out of the ForSight Labs ophthalmic incubator started by noted innovator Eugene de Juan, Jr., MD.
"In 2005, I witnessed the presentation at the American Society of Retina Specialists meeting of the dramatic visual improvements from monthly injections of Lucentis for choroidal neovascularization associated with AMD, which profoundly changed ophthalmology," said Dr. de Juan in a press release. "The ForSight Vision4 PDS was developed specifically to continue to enhance the treatment of patients with retinal diseases.”
In recent years, Genentech has been moving the sustained-release technology through early-stage clinical trials. Currently, the company is conducting the 220-patient phase 2 LADDER study that, if successful, would bring doctors and patients one step closer to a less burdensome treatment regimen requiring fewer office visits and injections.
Genentech researchers have long believed that ranibizumab could be successful in a sustained-release format, because the drug has the stability to remain effective for months when placed in an implant.1
In the small phase 1 study, the RPDS implant was well tolerated and showed an improvement in visual acuity comparable to monthly Lucentis injections, establishing proof of concept for the system. Genentech’s RPDS implant also has received FDA fast-track designation, which is designed to facilitate development and expedite review of drugs to treat serious conditions and fill an unmet medical need.
“With the investigation of the RPDS implant, we hope to provide patients with the maximum benefits of treatment with Lucentis while reducing the number of office visits and injections they require,” said Jill Hopkins, MD, medical director, Genentech Ophthalmology, in an announcement about the product.
“Inconsistency in treatment adherence can sometimes result in vision loss,” said Richard F. Dreyer, MD, LADDER clinical investigator. “If successful, the RPDS implant could become a useful tool to better manage wet AMD by providing a consistent level of treatment and potentially result in better long-term visual outcomes.”2
"This transaction marks the successful culmination of an early and ongoing collaboration between the ForSight Vision4 team and the team at Genentech, and puts the PDS technology on a path to revolutionize retinal therapies for patients worldwide," said K. Angela Macfarlane, president and CEO of ForSight Vision4, Inc, in a press release. LADDER is an interventional, randomized, double-blind, active comparator multicenter study.
Other Companies Study Sustained-Release Therapies
In a related development, Regeneron has recently begun its own sustained-release initiative for its anti-VEGF drug Eylea (aflibercept), which is currently delivered via regular intravitreal injections. Ocular Therapeutix is now developing proprietary sustained-release hydrogel-based drug delivery depots that can be implanted and formulated with both small- and large-molecule pharmaceuticals, such as tyrosine kinase inhibitors and protein-based anti-VEGFs, respectively, with the goal of delivering sustained and therapeutic levels of drugs to targeted ocular tissues. The formulation for Eylea is in preclinical development.
Alcon and pSivida are also active in developing sustained-release approaches to combat retinal disease. Alcon’s investigational small-molecule, single-chain antibody fragment brolucizumab (RTH258) has been identified as a drug that is particularly suited for use in a sustained-release format. pSivida developed the implant vehicles for both Iluvien and Retisert. RP
References
- Helzner J. Anthony P. (Tony) Adamis, MD: a giant in the fight against retinal disease. Retinal Physician, 2015;12(1):25-26. http://www.retinalphysician.com/issues/2015/jan-feb/innovation-in-retina
- Helzner J. Sustained-release delivery of Lucentis studied. Retinal Physician. 2016:13(1):10,12,15-17. http://www.retinalphysician.com/issues/2016/jan-feb/subspecialty-news
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