Nightstar reports proof of concept data from dose escalation in XIRIUS trial
Nightstar Therapeutics announced that positive preliminary safety and efficacy data of NSR-RPGR from the dose escalation study in the Phase 1/2 XIRIUS trial were presented at the EURETINA 2018 Congress. XIRIUS is a Phase 1/2, open-label, dose-ranging, single-eye clinical trial consisting of a dose escalation study and an expansion study with sites in both the U.S. and the U.K. The XIRIUS trial is intended to evaluate the safety, tolerability and efficacy of NSR-RPGR for the treatment of XLRP in patients with the RPGR mutation. Available safety data from the 15 treated patients in cohorts 1-5 indicates that NSR-RPGR was well-tolerated. The safety profile in the dose escalation study is generally consistent with that of surgical vitrectomy procedures and what has been observed in clinical trials of other ocular gene therapies. No serious adverse events related to treatment were reported and no early discontinuations or dose limiting toxicity were observed. Mild drug-related inflammation that potentially dampened efficacy was seen in the treated eyes of cohorts 4-5, with treatment efficacy observed to have been rescued in patients who received additional steroid treatment. Adverse events of varying severity and duration related to the vitrectomy procedure or drug have been observed in the dose escalation study such as retinal changes, intraocular inflammation and visual disturbances. The Data Monitoring Committee reviewed preliminary safety data for cohorts 1-5 and recommended escalation to cohort 6. The DMC also has not restricted pediatric enrollment in either the dose escalation study or expansion study. Based on the totality of results to date, Nightstar expects to initiate enrollment of the expansion study in the XIRIUS trial in the fourth quarter of 2018. The expansion study is intended to enroll approximately 30 adult and pediatric patients at a therapeutic dose informed by the dose escalation study and a low-dose control group of approximately 15 patients. Preliminary efficacy data from the expansion study is expected to be available in mid-2019, with one-year follow-up data expected to be available in 2020.