No abstract

etinitis pigmentosa (RP) is a progressive, inherited, monogenic or rarely digenic 1 blinding disease caused by mutations in more than 71 different genes (https://sph.uth.edu/retnet/ sum-dis.htm). It affects more than 2 million people worldwide. With the exception of a gene replacement therapy for one form of early-onset RP caused by mutation in the gene RPE65 (ref. 2 ), there is no approved therapy for RP.Optogenetic vision restoration 3-5 is a mutation-independent approach for restoring visual function at the late stages of RP after vision is lost [6][7][8][9] . The open-label phase 1/2a PIONEER study (ClinicalTrials.gov identifier: NCT03326336; the clinical trial protocol is provided in the Supplementary Text) was designed to evaluate the safety (primary objective) and efficacy (secondary objective) of an investigational treatment for patients with advanced nonsyndromic RP that combines injection of an optogenetic vector (GS030-Drug Product (GS030-DP)) with wearing a medical device, namely light-stimulating goggles (GS030-Medical Device (GS030-MD)). The proof of concept for GS030-DP and the GS030-DP dose used in the PIONEER clinical trial were established in nonhuman primate studies 10,11 .The optogenetic vector, a serotype 2.7m8 (ref. 12 ) adenoassociated viral vector encoding the light-sensing channelrhodopsin protein ChrimsonR fused to the red fluorescent protein tdTomato 13 , was administered by a single intravitreal injection into the worse-seeing eye to target mainly foveal retinal ganglion cells 10 . The fusion protein tdTomato was included to increase the expression of ChrimsonR in the cell membrane 10 . The peak sensitivity of ChrimsonR-tdTomato is around 590 nm (amber color) 13 . We chose ChrimsonR, which has one of the most red-shifted action spectra among the available optogenetic sensors because amber light is safer and causes less pupil constriction 10 than the blue light used to activate many other sensors. The light-stimulating goggles capture images from the visual world using a neuromorphic camera that detects changes in intensity, pixel by pixel, as distinct events 14 . The goggles then transform the events into monochromatic images and project them in real time as local 595-nm light pulses onto the retina (Extended Data Fig. 1). Results Safety of the optogenetic vector and light-stimulating goggles.In this article, we describe the partial recovery of vision in one participant of the PIONEER study. At the inclusion in the study, this 58-year-old male, who was diagnosed with RP 40 years ago, had a visual acuity limited to light perception. The worse-seeing eye was treated with 5.0 × 10 10 vector genomes of optogenetic vector. Both before and after the injection, we performed ocular examinations and assessed the anatomy of the retina based on optical coherence tomography images, color fundus photographs and fundus autofluorescence images taken on several occasions over 15 visits spanning 84 weeks according to the protocol (Extended Data Fig. 2). We monitored potential intraocular inflammation a...

eudract.ema.europa.eu Identifier: 2007-000847-89

Introduction: Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAFcontaining ADCs. Methods: Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal