With its patents on Lucentis set to expire in a few years and clinical trials of at least three Lucentis biosimilars underway, Roche’s recent acquisition of ForSight VISION4 is seen by many as the latest strategic move to protect its Lucentis franchise for the foreseeable future.
The ForSight VISION4 acquisition gives Roche and its subsidiary, Genentech, exclusive control of the Port Delivery System (PDS) ForSight VISION4 has been developing for sustained delivery of Lucentis (ranibizumab) for treatment of retinal disease. Genentech last year received FDA approval for its first proprietary Lucentis delivery platform, a 0.5-mg prefilled syringe for treatment of age-related macular degeneration (AMD) and macular edema after retinal vein occlusion (RVO).
PDS uses a new formulation of ranibizumab that could lead to a patentable drug for Roche and Genentech, whose Lucentis patents expire in 2020 and 2022 in the US and Europe, respectively. Whatever formulation of ranibizumab is settled on after testing will be unique and optimized for sustained delivery, Jill Hopkins, MD, global development team lead for Genentech’s sustained-delivery program for Lucentis, told Eye on Innovation.
Refillable Reservoir System
PDS is a refillable reservoir system that has a diffusion-control mechanism designed to release Lucentis over a period of time. A surgeon inserts the pre-filled device under the conjunctiva and then closes the conjunctiva over it.
Refilling the port is an in-office procedure that uses a proprietary refill needle system, called a customized exchange needle. It simultaneously introduces fresh drug into the reservoir while collecting any remaining previous implant contents. This maintains drug potency in the implant and provides predictable drug release after each refill.
A big reason for utilizing a system like this is to reduce treatment burden for patients on anti-VEGF therapies, which can require intravitreal injections as frequently as every month. In addition to extending the length of time between doctor visits, the task of injecting the anti-VEGF agent itself would be easier. “It’s certainly anticipated that the system would be associated with less discomfort than a standard intravitreal injection as it doesn’t penetrate the sclera,” Dr. Hopkins said. “You just go through the conjunctiva into the little port reservoir.”
Daniel Kiernan, MD, a retina specialist at Ophthalmic Associates of Long Island, agrees that refilling the port would be less invasive than current injections. “It would be more like doing a subconjunctival injection at a specific point,” he said.
Finding the Right Dose
Dr. Kiernan has been an investigator for a number of Genentech trials, and is familiar with the LADDER extended-treatment trial. Now in Phase II, that trial is looking at three different formulations of ranibizumab in patients with subfoveal neovascular AMD. Each study arm receives different doses over time.
“The dose ranging is really critical to identify the optimal concentration of drug to deliver in a sustained-delivery device, so we can identify the dose that’s going to be associated with the best possible length of duration and the best possible patient outcome,” Dr. Hopkins said.
Another potential benefit of the PDS is to increase the efficacy of treatment. “The potential to allow for sustained intravitreal drug release between refills may allow us to have a more consistent pharmacokinetics profile, fewer peaks and troughs, and potentially offer better long-term vision,” Dr. Hopkins said. The current trial is the first one of what she called “true sustained delivery” of ranibizumab over an extended time.
Long-term cost is also a consideration, Dr. Kiernan said. “Hopefully, the costs will be more contained as time goes on, and I think that will parallel the reduced number of treatments we have to give,” he said. “The question in everybody’s mind is, if you can get away with fewer injections, is that product still going to be as good as monthly injections with the competitor? I certainly think if you can do fewer injections and get the same results, and you can streamline the implementation of this delivery system, that is going to catch more market share.”
PDS may also have other applications going forward, Dr. Kiernan said. “This is really kind of the new cutting-edge horizon of drug delivery, especially for AMD. Eventually, it will be the same for diabetic macular edema [DME] and RVO. We already have some extended-dose implants for posterior uveitis and DME, such as steroids, so it’s just been a matter of time for anti-VEGF to make that entry into extended release.”
The acquisition of PDS gives Roche and Genentech “potential for a platform technology approach,” Dr. Hopkins said.
Steve Lenier has worked with medical content for almost 30 years, with an emphasis on ophthalmology since 2005. – @SteveLenier