Novel technique to deliver and retain cell therapy at target site
Investigators are hoping that a new suprachoroidal technique for subretinal delivery will optimise the safety and efficacy of palucorcel (CNT02476, Janssen BioTherapeutics) as a treatment for geographic atrophy (GA).
Palucorcel represents a cell therapy approach for reversing vision loss from dry age-related macular degeneration (AMD). It comprises allogenic, non-dividing human umbilical tissue-derived cells secreting cytokines with trophic effects that are believed to be beneficial for treating retinal diseases – most notably, dry AMD.
The suprachoroidal approach for subretinal delivery was implemented in the ongoing Phase 2b PRELUDE study and described by Christopher D Riemann MD at the 16th EURETINA Congress in Copenhagen, Denmark.
“Palucorcel has exciting potential for treating degenerative retinal disorders by favourably influencing diseased or dying cells. To optimise the effect of the trophic factor release, the cell product needs to be in close vicinity to the target cells, and to successfully treat GA, a non-retinal penetrating delivery is required to prevent the cells from escaping into the vitreous cavity,” explained Dr Riemann, Cincinnati Eye Institute, and Volunteer Professor of Ophthalmology, University of Cincinnati, USA.
Palucorcel was first investigated in a Phase 1A trial enrolling seven patients with retinitis pigmentosa and then advanced into a Phase 1/2A trial including 33 patients with GA. In those earlier studies, the cell product was successfully placed into the subretinal space with a microcatheter delivery system via an ab externo approach and was well tolerated.
There were no problems with immune reaction, and 25% of the GA patients gained three lines of vision. However, the surgery was long, complicated, required two surgeons, and was associated with an unacceptably high retinal detachment rate.
A team of engineers, surgical human form factor experts and surgeons collaborated to develop a technique to address the surgical challenges. The suprachoroidal approach was chosen from among four candidate techniques that were rigorously evaluated in a porcine model to assess procedural safety, complexity and efficiency. As a next step, enhancements were made to the prototype instrumentation and surgical procedure. Briefly, the delivery procedure involves insertion of an eye chandelier port, conjunctival dissection, stamping the sclera with a suture template guide and placement of a suture loop assembly for guiding and stabilising the delivery cannula.
The cannula that contains a micro-needle is inserted through the sclerotomy into the suprachoroidal space and advanced posteriorly to the target delivery site. Next, the needle is advanced through the choroid into the subretinal space and BSS is infused to create an entry bleb. Palucorcel is injected after confirming the retina has not been penetrated. Then, the needle is retracted, the cannula removed, and the sclerotomy sutured closed.
“There is no reason that this procedure could not be used for other drugs and substances that need to access the subretinal space,” Dr Riemann said.
Christopher D Riemann: firstname.lastname@example.org