Ocugen Announces Positive FDA Interactions Regarding Optical Gene Therapy and Orthopedic Cell Therapy


The agency granted OCU400 orphan drug designation for additional indications and agreed to a phase 3 trial design for NeoCart.

Ocugen’s OCU400, an investigational gene therapy intended to treat various inherited retinal diseases, has received orphan drug designation (ODD) from the FDA for retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA).1

OCU400 utilizes Ocugen’s Modifier Gene Therapy Platform, which may allow the product to treat multiple retinal diseases. The therapy is designed to deliver a functional copy of the nuclear hormone receptor gene NR2E3 via an adeno-associated viral (AAV) vector with the intention of resetting retinal homeostasis.2,3 It is currently being investigated in a multicenter, open-label, dose ranging phase 1/2 clinical trial (NCT05203939).

“Receiving orphan drug designation is incredibly encouraging at this stage in the development of OCU400,” Arun Upadhyay, PhD, chief scientific officer, Ocugen, said in a statement regarding the news.1 “We are excited by the potential of OCU400, a nuclear hormone-based modifier gene therapy product, to treat RP and LCA in a gene agnostic manner. We look forward to working collaboratively with the FDA and other agencies to progress OCU400 through clinical development to commercialization.”

OCU400 previously received ODDs from the FDA for PDE6B gene mutation-associated retinal diseases, RHO mutation-associated retinal degeneration, NR2E3 mutation-associated retinal degeneration, and CEP290 mutation-associated retinal degeneration.3 It also was granted orphan medicinal product designation by the European Commission for the treatment of both RP and LCA in February 2021.4

Last week, Ocugen also announced that its proposed design for a phase 3 clinical trial of NeoCart, an investigational regenerative cell therapy intended to repair full-thickness lesions in the knee cartilage of adult patients, was agreed to by the FDA.5

NeoCart is meant to “enhance the autologous cartilage repair process by merging a patient’s own cells with a fortified 3-D scaffold designed to accelerate healing and reduce pain.” It previously received regenerative medicine advanced therapy (RMAT) designation from the FDA for the above indication in May of this year.6 The company plans to evaluate NeoCart in comparison to chondroplasty in the randomized trial.5 The study will include patients with 1 or 2 articular cartilage lesions with a total surface area of 1-3 cm2.

“We are eager to get started on the final phase of NeoCart development and pleased at the outcome of our discussions with the FDA,” Shankar Musunuri, chairman, chief executive officer, and co-founder, Ocugen, said in a statement regarding the news.5 “With this guidance, Ocugen has a clear path forward for the first candidate in our regenerative cell therapy program.”

NeoCart was previously evaluated in a phase 3 trial (NCT01066702) by Histogenics, a company that later merged withOcugen in 2019.7 The trial evaluated NeoCart in comparison to microfracture, but failed to meet its primary end point.8 In subsequent discussions with the FDA, the agency indicated that while some of the data from the trial was compelling, a new phase 3 clinical trial would be needed before it would accept a biologics license application for filing. Ocugen now intends to submit an investigational new drug amendment for the initiation of the new trial in late 2023 or early 2024.5 Ocugen also announced that a new current Good Manufacturing Practice cell therapy manufacturing facility is under construction that will support clinical and commercial production of NeoCart.

1. Ocugen announces OCU400 receives orphan drug designations for retinitis pigmentosa and leber congenital amaurosis. News release. Ocugen, Inc. December 15, 2022.https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-ocu400-receives-orphan-drug-designations 
2. Ocugen announces completion of dosing in OCU400 phase 1/2 cohort 2. News release. Ocugen, Inc. October 12, 2022. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-completion-dosing-ocu400-phase-12-cohort-2 
3. Ocugen receives fourth FDA orphan drug designation for the same product, OCU400 (AAV-NR2E3) gene therapy, for the treatment of another key inherited retinal disease (IRD), PDE6B gene mutation-associated retinal diseases. News release. Ocugen, Inc. August 10, 2022.https://ir.ocugen.com/news-releases/news-release-details/ocugen-receives-fourth-fda-orphan-drug-designation-same-product
4. European Commission grants Ocugen orphan medicinal product designation for gene therapy product candidate, OCU400, for the treatment of both retinitis pigmentosa and leber congenital amaurosis. News release. Ocugen, Inc.February 23, 2021. https://ir.ocugen.com/news-releases/news-release-details/european-commission-grants-ocugen-orphan-medicinal-product 
5. Ocugen announces phase 3 confirmatory clinical trial agreement for NeoCart. News release. Ocugen, Inc. December 16, 2022. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-phase-3-confirmatory-clinical-trial-agreement 
6. Ocugen announces new cell therapy program following FDA Regenerative Medicine Advanced Therapy (RMAT) recognition. News release. Ocugen. May 24, 2022. https://www.biospace.com/article/releases/ocugen-announces-new-cell-therapy-program-following-fda-regenerative-medicine-advanced-therapy-rmat-recognition/ 
7. Ocugen announces completion of its merger with Histogenics to create Nasdaq-listed clinical-stage company developing novel ocular gene therapies and biotherapeutics. News release. Ocugen, Inc. September 30, 2019. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-completion-its-merger-histogenics-create-nasdaq 
8. United States Security and Exchange Commission website. Histogenics Corporation Form 10-K. Accessed December 20, 2022.https://www.sec.gov/Archives/edgar/data/1372299/000156459019008830/hsgx-10k_20181231.htm 
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