Real-World Safety and Effectiveness of Voretigene Neparvovec : Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study

Voretigene neparvovec (VN) is the first available gene therapy for patients with biallelic RPE65-mediated inherited retinal dystrophy who have sufficient viable retinal cells. PERCEIVE is an ongoing, post-authorization, prospective, multicenter, registry-based observational study and is the largest study assessing the real-world, long-term safety and effectiveness of VN. Here, we present the outcomes of 103 patients treated with VN according to local prescribing information. The mean (SD) age was 19.5 (10.85) years, 52 (50.5%) were female, and the mean (SD) duration of the follow up was 0.8 (0.64) years (maximum: 2.3 years). Thirty-five patients (34%) experienced ocular treatment-emergent adverse events (TEAEs), most frequently related to chorioretinal atrophy (n = 13 [12.6%]). Eighteen patients (17.5%; 24 eyes [13.1%]) experienced ocular TEAEs of special interest, including intraocular inflammation and/or infection related to the procedure (n = 7). The mean (SD) changes from baseline in full-field light-sensitivity threshold testing (white light) at month 1, month 6, year 1, and year 2 were -16.59 (13.48) dB (51 eyes), -18.24 (14.62) dB (42 eyes), -15.84 (14.10) dB (10 eyes), and -13.67 (22.62) dB (13 eyes), respectively. The change in visual acuity from baseline was not clinically significant. Overall, the outcomes of the PERCEIVE study are consistent with the findings of VN pivotal clinical trials

Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag

BACKGROUND The aim of this study was to compare the effectiveness and tolerability of a chronobiotic (melatonin) with a hypnotic (zolpidem) and the combination of both substances to alleviate jet lag symptoms associated with eastward travel. METHODS This double-blind, randomized, placebo-controlled study is based on 137 volunteers flying from Switzerland to the American continent and back (6-9 time zones). The participants either received melatonin 5 mg (n = 35), zolpidem 10 mg (n = 34), a combination thereof (n = 29) or placebo (n = 39) on the eastbound flight back to Switzerland and once daily at bedtime on 4 consecutive days after the flight. The test battery included daily sleep logs, symptoms questionnaires, and the Profile of Mood States (POMS). Also, on the last treatment day, Visual Analog Scales (VAS) were completed to assess overall jet lag ratings and treatment effectiveness. Baseline data were collected on 4 consecutive days 2 wk after the flight. During post-flight treatment and baseline, motor activity was assessed in a subgroup of 49 subjects using wrist-worn ambulatory monitors. RESULTS The self-rated sleep quality was significantly improved by zolpidem, especially during the night flight. Subjects taking zolpidem reported significantly less jet lag and zolpidem was rated as the most effective jet lag medication. However, zolpidem and the combination melatonin/zolpidem were less well tolerated than melatonin alone; adverse event reports included nausea, vomiting, amnesia and somnambulia to the point of incapacitation. Confusion, morning sleepiness and nausea were highest in the combination group. CONCLUSIONS All active treatments led to a decrease of jet lag severity with zolpidem being the most effective treatment, particularly in facilitating sleep on night flights. Potential individual adverse reactions to this hypnotic have to be considered

Efficacy and safety of ranibizumab 0.5 mg in Chinese patients with visual impairment due to diabetic macular edema: results from the 12-month REFINE study.

PURPOSE To demonstrate the efficacy and safety of ranibizumab 0.5 mg pro re nata (PRN) versus laser photocoagulation for the treatment of Chinese patients with visual impairment due to diabetic macular edema (DME). METHODS REFINE was a phase III, 12-month, double-masked, multicenter, laser-controlled study in patients (aged ≥ 18 years) with DME. Patients were randomized 4:1 to receive either ranibizumab 0.5 mg or laser dosing regimen. Efficacy was evaluated as mean average change in best-corrected visual acuity (BCVA) from Months 1 to 12 versus baseline (primary endpoint), anatomical outcomes, treatment exposure, and safety were also assessed. RESULTS Ranibizumab was statistically superior (p < 0.001) to laser treatment, with a mean average BCVA gain of 6.8 letters (ranibizumab) over 12 months versus 1.1 letters (laser). At Month 12, mean BCVA gain was 7.8 letters (ranibizumab) and 2.5 letters (laser) from baseline. Patients in the ranibizumab arm received a mean number of 7.9 intravitreal injections, whereas those in the laser arm received a mean of 2.1 treatments. There were no new safety signals. CONCLUSION Ranibizumab 0.5 mg PRN demonstrated a statistically significant and clinically meaningful treatment effect versus laser and was well tolerated in Chinese patients with visual impairment due to DME over 12 months

Real-World Safety and Effectiveness of Voretigene Neparvovec: Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study

Voretigene neparvovec (VN) is the first available gene therapy for patients with biallelic RPE65-mediated inherited retinal dystrophy who have sufficient viable retinal cells. PERCEIVE is an ongoing, post-authorization, prospective, multicenter, registry-based observational study and is the largest study assessing the real-world, long-term safety and effectiveness of VN. Here, we present the outcomes of 103 patients treated with VN according to local prescribing information. The mean (SD) age was 19.5 (10.85) years, 52 (50.5%) were female, and the mean (SD) duration of the follow up was 0.8 (0.64) years (maximum: 2.3 years). Thirty-five patients (34%) experienced ocular treatment-emergent adverse events (TEAEs), most frequently related to chorioretinal atrophy (n = 13 [12.6%]). Eighteen patients (17.5%; 24 eyes [13.1%]) experienced ocular TEAEs of special interest, including intraocular inflammation and/or infection related to the procedure (n = 7). The mean (SD) changes from baseline in full-field light-sensitivity threshold testing (white light) at month 1, month 6, year 1, and year 2 were &minus;16.59 (13.48) dB (51 eyes), &minus;18.24 (14.62) dB (42 eyes), &minus;15.84 (14.10) dB (10 eyes), and &minus;13.67 (22.62) dB (13 eyes), respectively. The change in visual acuity from baseline was not clinically significant. Overall, the outcomes of the PERCEIVE study are consistent with the findings of VN pivotal clinical trials