New Medicines

X-linked retinitis pigmentosa (XLRP)


New molecular entity

Development and Regulatory status

Phase III Clinical Trials
Phase II Clinical Trials
Phase III Clinical Trials
Apr 20Has orphan drug status in EU [8].
Apr 20Analysts predict US launch in 2023 and ex-US launch in 2024, both with 35% chance of success [8].
Apr 19Receives Fast Track and Orphan designation in US.[5]


XLRP, caused by RPGR gene mutation, leads to poor rod and cone function, retinal degeneration and blindness. A single injection of AAV-RPGR gene therapy delivers correct gene into the retina to slow retinal degeneration and preserve visual function.[1,2]
The prevalence of RP is estimated at ~1 in 5,000 individuals. XLRP accounts for 6-10% of cases [3,4]. This means ~ 1000 people in England are likely to affected at on time but not all will be eligible for this.
X-linked retinitis pigmentosa (XLRP)
Subretinal injection

Trial or other data

May 21Although XIRIUS did not meet its primary endpoint, Biogen saw positive trends in other pre-specified clinically relevant endpoints, such as a measure of visual acuity under low light conditions. Biogen is further evaluating the data before communicating potential next steps [11].
May 21Company announces the gene therapy failed to hit the primary endpoint of the Phase II/III XIRIUS trial [10].
Apr 20No information available on progress of PII/III expansion study. According to a previously released press announcement, the primary efficacy endpoint will evaluate changes in retinal sensitivity following treatment with NSR-RPGR. Secondary endpoints include both anatomical and functional endpoints of efficacy and safety similar to those evaluated in the dose escalation study as well as exploratory efficacy endpoints such as mobility maze assessments. The eligibility criteria for the expansion study will include patients with functional impairment as measured by microperimetry and the presence of viable photoreceptors as indicated by ellipsoid zone measurements on optical coherence tomography. Patients will be randomized on a masked basis into one of three study arms: approximately 15 patients receiving a high-dose of NSR-RPGR in one-eye (2.5x10^11 genome particles, or gp); approximately 15 patients receiving a low-dose of NSR-RPGR in one-eye (5x10^10 gp); and approximately 15 patients receiving no treatment (no-sham, parallel control arm). The two treatment groups correspond to doses used in cohorts 5 and 3 of the dose escalation study, respectively. A standardized eight-week steroid regimen will be included to maximize any potential treatment benefit. The Phase 2/3 expansion study is expected to begin by the end of 2018. Preliminary efficacy data is expected to be available in mid-2019, which would serve as the basis for discussions with regulatory agencies on potential Phase 3 requirements. One-year follow-up data from the expansion study is expected to be available in 2020 [8,9,10].
Apr 20PI/II XIRIUS trial is recruiting; collection of primary outcome data is due to complete Mar 21 [9].
Feb 20Initial results from an ongoing PI/II open label, multi-centre, dose ecalation trial (NCT03116113) of AAV8-RPGR in 46 adults and children with XLRP published. [1,7] After gene therapy, there was a dose–response effect across trial cohorts in terms of gains in visual function in treated eyes vs. untreated fellow eyes. Mid-dose pts showed gains in retinal sensitivity and reversal of some visual field loss by month 1 sustained through to month 6. Gene therapy was well tolerated with no serious adverse events related to treatment and no dose limiting toxicity observed. In cohorts 4 and 5, mild drug-related inflammation was seen which potentially dampened efficacy but efficacy was rescued by additional steroid treatment. The study is expected to complete in Aug 2020 [1,5,7].
Mar 19Nightstar Therapeutics initiates the PII/III expansion study to evaluate the safety and efficacy of NSR RPGR in patients with a diagnosis of X-linked retinitis pigmentosa (XLRP) due to RPGR mutations, as confirmed by genetic testing. The dose-expansion trial is enrolling approximately 45 patients in the US and the UK [8].
Mar 17Nightstar initiated the PI/II XIRIUS trial to assess the safety and tolerability of AAV RPGR gene therapy in patients with patients with X-linked retinitis pigmentosa (NSR-RPGR-01; NCT03116113) [8].