Delving into the Latest Updates on Palucorcel with Synapse

Overview

Basic Info

Drug Type

Stem cell therapy

Synonyms

Target-

Mechanism

Cell replacements

Therapeutic Areas

Nervous System DiseasesCongenital DisordersEye Diseases+ [1]

Active Indication-

Inactive Indication

Originator Organization

Janssen Global Services LLC

Active Organization-

Inactive Organization

Janssen Research & Development LLC

Janssen Pharmaceuticals, Inc.Centocor, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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The purpose of the study is to evaluate the efficacy and safety of CNTO 2476 cells administered into the subretinal space by the suprachoroidal surgical approach and the subretinal access kit (SRAK-02) in participants with visual acuity impairment associated with Geographic Atrophy (GA) secondary to Age Related Macular Degeneration (AMD).

Start Date09 Apr 2018

Sponsor / Collaborator

Janssen Pharmaceuticals, Inc.

JPRN-JapicCTI-163414 / Unknown statusPhase 2

A Phase 2, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Subretinal Administration of CNTO 2476 in Subjects with Visual Acuity Impairment Associated with Geographic Atrophy (GA) Secondary to Age Related Macular Degeneration (AMD)

Start Date31 Mar 2017

Sponsor / Collaborator

Janssen Pharmaceuticals, Inc.

JPRN-jRCT1080223359 / Unknown statusPhase 2

A Phase 2, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Subretinal Administration of CNTO 2476 in Subjects with Visual Acuity Impairment Associated with Geographic Atrophy (GA) Secondary to Age Related Macular Degeneration (AMD)

Start Date31 Oct 2016

Sponsor / Collaborator

Janssen Pharmaceuticals, Inc.

100 Clinical Results associated with Palucorcel

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100 Translational Medicine associated with Palucorcel

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100 Patents (Medical) associated with Palucorcel

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5

Literatures (Medical) associated with Palucorcel

01 Apr 2020·Ophthalmology Retina

Safety and Efficacy of Subretinally Administered Palucorcel for Geographic Atrophy of Age-Related Macular Degeneration

Article

Author: Baldassarre, James S ; Spencer, Rand ; Chang, Tom ; Hickson-Curran, Sheila B ; Samuel, Michael A ; Leiderman, Yannek I ; Keane, Michael ; Williams, George A ; Slakter, Jason S ; Kitchens, John W ; Heier, Jeffrey S ; Riemann, Christopher D ; Ho, Allen C

PURPOSETo evaluate safety and successful use of a novel subretinal delivery system and suprachoroidal surgical approach and safety and activity of human umbilical tissue-derived cells (palucorcel) via a novel delivery system in patients with geographic atrophy (GA).DESIGNMulticenter, open-label phase 2b study.PARTICIPANTSParticipants were 55 to 90 years with GA secondary to age-related macular degeneration (AMD) and best-corrected visual acuity (BCVA) of 20/80 to 20/800. Exclusion criteria included neovascular AMD in the intervention eye, glaucoma with intraocular pressure of 25 mmHg or more, or other significant ophthalmologic conditions.METHODSParticipants received a subretinal injection of palucorcel, 3.0 × 10⁵ cells in 50 μl, using the custom-designed delivery system and surgical procedure.MAIN OUTCOME MEASURESSafety assessments included treatment-emergent adverse events (AEs), immunologic assessments, and ophthalmologic evaluations. Efficacy was evaluated as change in mean number of BCVA letters from baseline, proportion of participants gaining 15 BCVA letters or more, and growth rate of GA lesions at 12 months.RESULTSSurgery and palucorcel administration were performed in 21 participants at 8 sites by 8 different surgeons. At baseline, median total area of GA was 13.4 mm² and median BCVA was 43 letters in the intervention eye. Eye-related AEs occurred in 76% of participants (16/21), including conjunctival hemorrhage (n = 5), retinal hemorrhage (n = 4), and vitreous floaters (n = 4). Most AEs were mild and resolved within 1 month. No serious AEs, no retinal detachment or perforation, and no significant changes in intraocular pressure occurred. At month 12, mean change in BCVA from baseline was -5.9 letters correct (standard deviation, 13.0 letters correct) in the intervention eye and -3.7 letters correct (standard deviation, 9.0 letters correct) in the fellow eye. No participants showed improvement of 15 letters or more in the intervention eye, and 3 participants lost more than 15 letters by month 1. No apparent effect of treatment was observed.CONCLUSIONSPalucorcel was delivered successfully to the targeted subretinal site using a novel delivery system and suprachoroidal approach for most participants; however, improvement in GA area, retardation of growth, or visual acuity were not demonstrated.

21 Mar 2018·The Journal of NeuroscienceQ1 · MEDICINE

Subretinal Human Umbilical Tissue-Derived Cell Transplantation Preserves Retinal Synaptic Connectivity and Attenuates Müller Glial Reactivity

Q1 · MEDICINE

Article

Author: Harris, Ian R ; Koh, Sehwon ; Chen, William J ; Lu, Bin ; Saylor, Joshua ; Girman, Sergey ; Eroglu, Cagla ; Wang, Shaomei ; Dejneka, Nadine S

Human umbilical tissue-derived cells (hUTC or palucorcel) are currently under clinical investigation for the treatment of geographic atrophy, a late stage of macular degeneration, but how hUTC transplantation mediates vision recovery is not fully elucidated. Subretinal administration of hUTC preserves visual function in the Royal College of Surgeons (RCS) rat, a genetic model of retinal degeneration caused byMertkloss of function. hUTC secrete synaptogenic and neurotrophic factors that improve the health and connectivity of the neural retina. Therefore, we investigated the progression of synapse and photoreceptor loss and whether hUTC treatment preserves photoreceptors and synaptic connectivity in the RCS rats of both sexes. We found that RCS retinas display significant deficits in synaptic development already by postnatal day 21 (P21), before the onset of photoreceptor degeneration. Subretinal transplantation of hUTC at P21 is necessary to rescue visual function in RCS rats, and the therapeutic effect is enhanced with repeated injections. Synaptic development defects occurred concurrently with morphological changes in Müller glia, the major perisynaptic glia in the retina. hUTC transplantation strongly diminished Müller glia reactivity and specifically protected the α2δ-1-containing retinal synapses, which are responsive to thrombospondin family synaptogenic proteins secreted by Müller glia. Müller glial reactivity and reduced synaptogenesis observed in RCS retinas could be recapitulated by CRISPR/Cas9-mediated loss-of-Mertkin Müller glia in wild-type rats. Together, our results show that hUTC transplantation supports the health of retina at least in part by preserving the functions of Müller glial cells, revealing a previously unknown aspect of hUTC transplantation-based therapy.SIGNIFICANCE STATEMENTDespite the promising effects observed in clinical trials and preclinical studies, how subretinal human umbilical tissue-derived cell (hUTC) transplantation mediates vision improvements is not fully known. Using a rat model of retinal degeneration, the RCS rat (lackingMertk), here we provide evidence that hUTC transplantation protects visual function and health by protecting photoreceptors and preserving retinal synaptic connectivity. Furthermore, we find that loss ofMertkfunction only in Müller glia is sufficient to impair synaptic development and cause activation of Müller glia. hUTC transplantation strongly attenuates the reactivity of Müller glia in RCS rats. These findings highlight novel cellular and molecular mechanisms within the neural retina, which underlie disease mechanisms and pinpoint Müller glia as a novel cellular target for hUTC transplantation.

24 Jan 2018·Investigative Opthalmology & Visual ScienceQ2 · MEDICINE

A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety and Surgical Outcomes

Q2 · MEDICINE

ArticleOA

Author: Lynch, Jessica L. ; Keane, Michael ; Dejneka, Nadine S. ; de Smet, Marc D. ; Khan, I. John

PurposeThis study evaluated a new subretinal method for delivery of human or pig umbilical tissue-derived cells (hUTC or pUTC, respectively) using a novel subretinal injection cannula and suprachoroidal approach in Göttingen minipig eyes. hUTC (palucorcel) are currently under development for treating geographic atrophy in humans.MethodsTwenty-four Göttingen minipigs (divided into eight groups) were subretinally administered palucorcel, pUTC, or vehicle. In some cases, fluorescently labeled cells and vehicle were administered. Conjunctival cutdown and sclerotomy were performed, then a flexible cannula containing a microneedle was inserted and advanced into the suprachoroidal space. The microneedle was deployed and visualized; 50 μL cells (target concentration, 11.2 × 106 cells/mL [560,000 cells/eye]) or vehicle was injected subretinally. Safety outcomes were evaluated.ResultsFor all animals, cells and vehicle were successfully administered. Labeled cells or fluorescent vehicle were contained in the subretinal bleb, without leakage into the vitreous. No retinal detachment or vitreous traction band was identified by ophthalmologic examination. At all time points, observed microscopic changes were attributable to experimental procedures. On histopathology immediately after injection, localized retinal detachments were seen, along with focal retinal, choroidal, and/or scleral discontinuities. A moderate inflammatory response was seen in a limited number of animals. In the allogeneic setting, no antibody responses were detectable. Anti-human UTC antibodies were detected in the xenogeneic setting.ConclusionsPalucorcel, pUTC, and vehicle were successfully administered to Göttingen minipigs using a novel subretinal injection cannula via a suprachoroidal surgical approach, with no significant adverse events; therefore, this technique appears to be feasible for further clinical development.

100 Deals associated with Palucorcel

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Age Related Macular Degeneration	Phase 2	US	Janssen Research & Development LLC	04 Dec 2015
Age Related Macular Degeneration	Phase 2	US	Janssen Research & Development LLC	04 Dec 2015
Geographic Atrophy	Phase 2	US	Janssen Research & Development LLC	04 Dec 2015
Geographic Atrophy	Phase 2	US	Janssen Research & Development LLC	04 Dec 2015
Vision, Low	Phase 2	US	Janssen Research & Development LLC	04 Dec 2015
Vision, Low	Phase 2	US	Janssen Research & Development LLC	04 Dec 2015
Visual Acuity	Phase 2	US	Janssen Research & Development LLC	04 Dec 2015
Visual Acuity	Phase 2	US	Janssen Research & Development LLC	04 Dec 2015
Retinitis Pigmentosa	Phase 2	US	Centocor, Inc.	01 Apr 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02659098 (PRELUDE, CTgov)	Phase 2	Age Related Macular Degeneration \| Geographic Atrophy \| Visual Acuity \| Vision, Low	21	CNTO 2476 (Palucorcel)+CNTO 2476	bbzwvhnvbn(eiscrebcov) = dpwpkljzgn tryaiwckty (zpmxxihxwi, boyyxhxdog - osqjsmzwiv) View more	-	23 Jun 2020