The European Union Registry Study (“EUROLIGHT”) will collect safety and clinical efficacy outcomes (BCVA and OCT) data from multiple centres that have been treating dry AMD subjects. The company suggested that the large registry “will collect data retrospectively with centres providing existing data from subjects who underwent PBM treatment every 4-6 months for up to three years”. The data will be used to support “reimbursement in multiple countries and provide important clinical information on real-world use of Valeda”. Dr. René Rückert, MD, MBA, Chief Medical Officer, LumiThera commented that a previous series of “trials demonstrated improvements of visual benefits with PBM treatments in a prospective randomized clinical trial (RCT) design.  The RCT results demonstrated clinical benefits in early to intermediate patients out to two years with anatomical evidence of slowing of AMD disease progression.”

The company have estimated that ~16,000 patients in Europe and Latin America have been treated to date on their PBM treatment. Dr. Oygunn Uthiem, MD, PhD, Department of Medical Biochemistry/Department of Ophthalmology, Oslo University Hospital stated that, “we are thrilled to be part of the EUROLIGHT study. We have treated over 350 patients in the last four years and have seen the real-world benefits of Valeda treatments in our patients. We have started to upload data into the registry database and have obtained over 70 informed consents from patients that want to be part of the study. Our patients have strictly followed the clinical trial protocols and been tested every 4-6 months, some for up to four years.”

In their current report, “IRDs” were traditionally driven by clinical / phenotypic features, as presented in the clinic however, as technological advances expand, the way by which IRDs were understood on the genetic aetiology and molecular biology, this presents challenges on how best to define therapeutic indications.  As a result, the COMP have recently reviewed “the state of the art” in IRDs “to assess what would be the best approach or set of disease terms to use as the ‘condition’ for orphan designation in this therapeutic setting”. The review was based on the scientific literature and the experience of how EU orphan designations have been applied to date and this recruited IRD clinical experts, regulators and patients in order to build practical consensus.

Figure 1. Genetic heterogeneity among the six major non-syndromic inherited retinal diseases (IRD). Numbers outside of the ellipses correspond to the number of non-syndromic IRD genes responsible for the specific disease, while numbers within the ellipses correspond either to disease-specific genes or to genes mutated in two or more diseases. The non-redundant total of genes associated with these non-syndromic IRD is 146.

RP: retinitis pigmentosa; LCA: Leber congenital amaurosis; CD/ CRD: cone dystrophy/cone-rod dystrophy; CSNB: congenital stationary night blindness; MD: macular dystrophy; EVR: exudative vitreoretinopathy. Reproduced unchanged with permission of authors Cremers FPM, Boon CJF, Bujakowska K, et al.7 © 2018 by the authors. Licensee MDPI, Basel, Switzerland under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Following deliberation by the clinical experts, regulators and patients on the literature review and expert consultation, COMP presented an optimised grouping for ODs with pharmacological approaches for in IRDs:

(Presented by Moseley et al, entitled “Inherited retinal dystrophies and orphan designations in the European Union”, Eur J Ophthalmol, 2024 Mar 18:11206721241236214. doi: 10.1177/11206721241236214. Distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).

The COMP has supported that three options may be available for orphan designation concerning the condition as: (i) an amended set of OD groups for therapies that might be used in a broad spectrum of conditions; (ii) a gene-specific designation for targeted therapies, and (iii) an occasional term for products that do not fit in the above two categories. Commenting on the review, the researchers stated that, “overall, this three-pillar strategy is considered to provide a robust yet flexible framework for orphan designations in the complex field of the genetic spectrum underlying inherited retinal dystrophies. By discarding the more rigid andsomewhat out-dated phenotypically derived classification scheme traditionally used for IRD conditions, COMP now has the possibility of using a more agile decision matrix that allows for orphan designations adapted to the clinical state-of-the-art of the treatment under discussion. In conclusion, the new strategy of COMP regarding ODs in the domain of IRDs reflects regulatory adaptation to the evolution of our scientific understanding in the field of rare eye diseases and the development of innovative therapies. Therefore, if confirmed as appropriate with future regulatory experience, it is not excluded that a similar approach could be applied to other disease areas in the near future.

The researchers collected medical records of patients diagnosed with Best disease from nine Israeli medical centres, including clinical data from ocular findings, electrophysiology results, and retina imaging.  Of the analysis, the researchers reported a total of 134 patients with Best disease and related conditions, estimating a prevalence to be 1 in 127,000, with higher rates among Arab Muslims (1 in 76,000) than Jews (1 in 145,000). Critical conserved domains were identified consisting of a high percentage of dominant missense mutations, primarily in transmembrane domains and the intracellular region (Ca2+ binding domain) of the BEST1 protein.

Figure 1 (A) The distribution of BEST1 mutated alleles in the studied set of Israeli patients compared to the alleles reported previously. The data were calculated and are presented in percent (%). Each bar represents the percentage of alleles associated with a certain clinical diagnosis among the Israeli cohort of BEST1 (orange) and worldwide (blue). (B) The distribution of mutated BEST1 alleles identified in patients from the Israeli cohort (left pie chart) and alleles reported worldwide (right pie chart) based on recessive/dominant alleles (inner circle) and the type of the mutation (outer circle). [Copyright from IOVS, under a Creative Commons license – Beryozkin et al., Investigative Ophthalmology & Visual Science February 2024, Vol.65, 39].

According to their publication, the researchers commented that, “to our knowledge, this is the largest cohort of patients with Best disease reported to date in the Israeli population and worldwide”. The information of these results may be extremely valuable which might benefit from the development of gene augmentation therapy or RNA editing therapy in due course. Their research team commented that “the findings from this research will enable us and other researchers to better understand the range of mutations that cause the disease, identify crucial functional domains, and explore possible correlations between genotypes and phenotypes. Ultimately, this knowledge will contribute to unravelling the molecular mechanisms underlying BVMD and guide the development of novel treatments”.