In the first months of 2020, positive results in gene therapy of X-linked retinitis pigmentosa (XLRP) have been reported. XLRP is an inherited genetic disorder that causes progressive vision loss, mainly in men. It begins in childhood with night blindness, progresses with the gradual reduction of the visual field and visual acuity, and leads to blindness in the fourth decade of life.
RPGR is one of the most frequent genes (10-20%) that causes RP, and it explains around 70-90% of the cases of XLRP. For this reason, it has been prioritized for gene therapy, and three independent clinical trials are currently underway. They are all based on a virus mediated addition (named gene addition therapy) of the normal gene to the eye of the patient by subretinal injection. The aim being to rescue the function of RPGR.
Three biotech companies promote the ongoing studies: MeiraGTx (in collaboration with the pharmaceutical company Janssen), Applied Genetic Technologies (AGTC) Corporation, and Biogen.
In March, the European Medicines Agency (EMA) awarded the MeiraGTx and Janssen gene therapy the priority medicine (PRIME) and advanced therapy medicinal product (ATMP) designations. It is the first RPGR gene therapy to be granted with these designations, based on the preliminary results of the clinical trial (NCT03252847) currently underway in the United Kingdom, at Moorfields Eye Hospital in London, and at three centers in the United States, including the Massachusetts Eye and Ear in Boston. The PRIME and ATMP designations will speed up the regulatory review and approval process if the data from the clinical trials are positive.
In January, Applied Genetic Technologies Corporation (AGTC) reported positive 6-month follow-up results of the clinical trial for RPGR gene therapy carried out in several US hospitals (NCT03316560), showing significant and lasting improvements in central visual sensitivity (for four of the evaluable eight patients) and in visual acuity (all nine patients treated centrally, seven of them saw a 5 letter or more improvement). AGTC also announced that patient recruitment for the two higher dose groups had concluded in February.
Finally, clinical researchers at the University of Oxford studying Biogen’s RPGR gene therapy (initially developed by Nightstar Therapeutics) recently published positive results in Nature Medicine, corresponding to a 6-month follow-up of the XIRIUS clinical trial (NCT03116113). This early-stage, safety-focused gene therapy trial, still ongoing in different ophthalmological institutions in the US and UK, showed clinically significant vision improvements in retinal sensitivity and visual fields, one month after a single injection and durability at 6 months.
These gene therapy trials open hopeful scenarios for RP patients carrying mutations in the RPGR gene and raise hopes for effective gene therapies to treat this disease.