MeiraGTx (Nasdaq: MGTX), has announced six-month data from an ongoing phase 1/2 clinical trial of AAV-RPGR for the treatment of patients with X-linked retinitis pigmentosa (XLRP). The research data  from the company showed that significant improvement in vision was demonstrated in the dose escalation phase of a clinical trial with AAV-RPGR, found to be generally well tolerated.  The company has developed a jointly collaborative programme with Janssen Pharmaceuticals, Inc. (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson.  The collaboration is aimed to develop and commercialize gene therapies for the treatment of inherited retinal diseases.

X-linked retinitis pigmentosa (XLRP) is an incurable genetic disease that causes blindness in males affecting approximately one in 15,000 people. The disease is caused by a defect in the RPGR gene (GTPase regulator gene) which is located on the X-chromosome. Together with mutations in RP2, these two genes account for a significant majority of cases of XLRP. Over 300 mutations occur in the RPGR gene, most of which in the open reading frame exon (ORF15), causing an abnormally short protein that is expressed in the connecting cilium of photoreceptors, and is an important component of all ciliated cells in the body.  Mutations in the RPGR gene can be associated with a rod-cone or cone-rod dystrophy phenotype. The most common presentation is as a rod-cone dystrophy. It is one of the most severe forms of RP with nyctalopia in most affected males before 10 years of age and progression to legal blindness by the third to fourth decade. The disorder is initially identified with difficulties in scotopic visual function, where there is a predominant loss of rod photoreceptors. Simultaneously, peripheral vision deteriorates, resulting in visual field constriction on perimetry findings. The majority of cases present with a rod-cone dystrophy-type disease progression, where central visual acuity is initially less impaired than the peripheral field loss. The fovea is ultimately affected in all cases during the late stages of the disease by subsequent cone photoreceptor degeneration.

According to the current study, the ongoing phase 1/2 study, termed “MGT009” is understood to consist of three phases: dose-escalation, dose-confirmation, and dose-expansion. In the dose-escalation phase (n=10), adults were administered low, intermediate, or high dose AAV-RPGR. Each patient was treated with subretinal delivery of AAV-RPGR in the eye that was more affected at baseline. The primary endpoint of the trial is safety, with secondary endpoints assessing changes in visual function at pre-specified timepoints post-treatment. At the six-month timepoint, significant improvement in retinal sensitivity was demonstrated in patients treated with low and intermediate dose AAV-RPGR. Improvement was evident at first post-treatment perimetry assessments at three months, with improvements generally sustained or increased at six months. Significant differences were observed in retinal sensitivity between treated and untreated eyes over time.  In particularly, significant differences in mean retinal sensitivity were observed between treated eyes and untreated eyes in an intermediate dose cohort: 1.02 dB (90% CI: 0.75, 1.31), while central visual field progression rate (V30) between treated eyes and untreated eyes showed both the low cohort, 1.10 dB-sr/year (90% CI: 0.10, 2.10) and intermediate cohort, 1.26 dB-sr/year (90% CI: 0.65, 1.86).  In their announcement, Alexandria Forbes, Ph.D., president and chief executive officer of MeiraGTx stated that  “we are pleased to share these encouraging initial results from our XLRP gene therapy trial and look forward to advancing this program into a Phase 3 trial. These early data suggest AAV-RPGR has the potential to address some of the key functional manifestations of this severe disease for which there is no currently available therapy.”