Janssen's Gene Therapy for X-Linked Retinitis Pigmentosa Receives EMA PRIME and ATMP Designations

Text | Ke Ke

On March 2, Xian Janssen, a subsidiary of Johnson & Johnson, announced that the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation and Advanced Therapy Medicinal Product (ATMP) status to its adeno-associated virus (AAV)-based gene therapy targeting the retinitis pigmentosa GTPase regulator (RPGR) for the treatment of X-linked retinitis pigmentosa (XLRP), a hereditary retinal disease. This is currently the only RPGR gene therapy program to receive PRIME designation, and Xian Janssen will accelerate the regulatory review process for the therapy’s market approval in Europe.

PRIME is a priority medicines scheme launched by the European Medicines Agency (EMA) in 2016, aimed at accelerating the review process for key medicines in areas of unmet medical need. Selected investigational products receive substantial support from the EMA in clinical trials and drug development to expedite the development and approval of innovative therapies. Similarly, the Advanced Therapy Medicinal Products (ATMP) designation primarily applies to human medicinal products based on gene therapy, somatic cell therapy, or tissue engineering. Products granted this eligibility status can receive regulatory, technical, and even financial support. Previously, this novel AAV-RPGR gene therapy had already received Fast Track designation from the U.S. Food and Drug Administration (FDA), as well as Orphan Drug Designation from both the FDA and the EMA.

This PRIME designation is based on data from the ongoing Phase 1/2 clinical trial (NCT03252847). Reportedly, this is an open-label, multicenter, dose-escalation Phase I/II study that enrolled 46 pediatric and adult male patients aged 5 years or older with X-linked retinitis pigmentosa (XLRP). The primary endpoint was the safety of the AAV-RPGR gene therapy, while the secondary endpoints included improvements in visual function, retinal function, and quality of life within 18 months. The trial is expected to be completed in November of this year.

Dr. James List, Head of the Global Therapeutic Area for Cardiovascular and Metabolism in Janssen’s Research & Development department, stated that the gene therapy’s receipt of PRIME and ATMP designations represents a significant milestone in the continuous advancement of the company’s retinal product portfolio, marking another major step forward in delivering transformative treatments to European patients with X-linked retinitis pigmentosa.

X-linked retinitis pigmentosa (XLRP) is one of the most severe forms of retinitis pigmentosa, with onset often occurring during adolescence and progressing to blindness in adulthood. Currently, there are no approved therapies available on the market. However, retinal diseases represent an ideal target for gene therapy, as most of the gene mutations causing these conditions have been identified, and the eye is, to some extent, an immune-privileged site. Xian Janssen’s AAV-RPGR gene therapy aims to treat the most common form of XLRP caused by RPGR gene mutations by slowing retinal degeneration and preserving visual function. Existing studies have demonstrated that intraocular delivery of gene therapies using adeno-associated virus (AAV) or lentiviral (LV) vectors does not lead to systemic side effects or significant immune responses. Most investigational therapies aim to introduce functional genes to restore normal expression of the defective genes.

MeiraGTx’s Investigational Product Pipeline

Source: Company Website

Xian Janssen’s ophthalmology clinical-stage product portfolio primarily includes the candidate products AAV-CNGA3 and AAV-CNGB3 for achromatopsia, a hereditary retinal disease, as well as AAV-RPGR for X-linked retinitis pigmentosa. The company is also expanding into more common ocular diseases by employing mRNA therapies to treat conditions such as wet age-related macular degeneration, diabetic retinopathy, and diabetic macular edema. AAV-RPGR, AAV-CNGB3, and AAV-CNGA3 are all currently in Phase I/II clinical development. The latter two gene therapies aim to restore cone cell function by delivering the therapeutic agents via subretinal injection to the retinal region where the majority of cone cells are located.

Xian Janssen’s Pipeline of Investigational Products

Source: Company Website

In January 2019, Xian Janssen entered into a global collaboration and license agreement with MeiraGTx, a clinical-stage gene therapy company. Under the agreement, Xian Janssen made an upfront payment of $100 million to secure exclusive options for MeiraGTx’s preclinical programs in its hereditary retinal disease pipeline. MeiraGTx is also eligible to receive up to $340 million in various milestone payments and sales royalties. Pursuant to the collaboration agreement, the two companies are jointly developing the AAV-RPGR gene therapy and have established a research partnership to explore new targets for other hereditary retinal diseases and to further advance AAV manufacturing technologies.

MeiraGTx is a biopharmaceutical company focused on the development of gene therapies, with research priorities in three major areas: ophthalmic diseases, salivary gland disorders, and neurodegenerative diseases. The company’s core strengths lie in viral vector design and optimization, gene therapy manufacturing, and transgene regulation technologies. Minor variations in capsid proteins can modulate the efficiency of gene delivery to different cell types, and selecting specific AAV capsids enables optimal targeting of particular cell populations. MeiraGTx utilizes adeno-associated virus (AAV) vectors and customizes them to optimize gene therapies for various diseases. Additionally, MeiraGTx’s gene regulation platform integrates on/off switches for gene expression into the vectors, which can be activated by small molecules. This allows gene therapies to be turned on or off based on patient needs and therapeutic dosing requirements.

References:

1、EMA PRIME status granted to Janssen’s inherited retinal disease gene therapy

2、European Medicines Agency Grants PRIME and Advanced Therapy Medicinal Product Designations to Janssen's RPGR Gene Therapy for X-Linked Retinitis Pigmentosa