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Clinical Perspectives on Gene Therapy for Retinal and Eye Diseases
Published in Yashwant Pathak, Gene Delivery, 2022
Devika S. Joshi, Gaurav M. Karve, Shrikant D. Joshi
In 2017, the USFDA has approved voretigene neparvovec (Luxturna Spark Therapeutics, Inc., Philadelphia, PA), for the treatment of biallelic RPE65 mutation-associated- LCA2(The first USFDA approved gene therapy for the eye) offering some hope for patients suffering from this condition.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In another example, voretigene neparvovec (LuxturnaTM), developed by Spark Therapeutics Inc, is a gene therapy used to treat adults and children with loss of vision due to inherited retinal dystrophy, a rare genetic disorder of the retina. Approved in 2018, LuxturnaTM can only be used while patients still have enough functioning cells left in the retina and when the disease is caused by mutations in the RPE65 gene responsible for production of the enzyme, all-trans retinyl isomerase, necessary for the normal functioning of retinal cells. The key point is that LuxturnaTM is injected directly (sub-retinally) into the eye, thus avoiding any systemic off-target effects which would not be the case for cancer therapies. Other applications of gene therapy approaches such as the treatment of human immunodeficiency virus (HIV) infections and correction of the mutation that causes sickle cell disease may soon become a reality.
Advancements in ocular gene therapy delivery: vectors and subretinal, intravitreal, and suprachoroidal techniques
Published in Expert Opinion on Biological Therapy, 2022
Kyle D Kovacs, Thomas A Ciulla, Szilárd Kiss
Inherited retinal diseases comprise a rapidly expanding area of interest for gene therapy applications given the accessibility and the monogenic nature of most IRDs [22]. Imaging is readily obtainable and easy to quantifiably track over time to monitor structural progression. However, multiple issues complicate clinical study of gene therapy in IRDs. Rare IRDs often lack well-established natural histories, and regulatory authorities generally do not recommend the fellow eye as a control. In this setting, the treated eye and contralateral eye are often at different disease stages at the time of clinical trial enrollment, and performing different procedures on each eye can lead to unmasking. The advanced nature of most IRDs being targeted in trials has also led to difficulties developing functional efficacy outcomes. Visual acuities are often not sufficiently sensitive in advanced IRDs, particularly for disorders predominantly affecting rods [23]. The study and approval of voretigene neparvovec addressed some of these concerns, facilitating a framework for future retinal gene therapy development.
Gene editing technology: Towards precision medicine in inherited retinal diseases
Published in Seminars in Ophthalmology, 2021
Brian G. Ballios, Eric A. Pierce, Rachel M. Huckfeldt
Using the only FDA-approved gene therapy for ophthalmology, voretigene neparvovec-rzyl priced at 850,000 USD for a bilateral dose as an example, a recent cost-effective analysis was presented using patient-data obtained from the study.129 Using cost inputs and the utility of differential results, the conclusion was that the therapy is cost-effective, with an incremental cost-effectiveness ratio (ICER) of 79,618 USD/QALY. These conclusions should be interpreted cautiously as, given the visual field loss that dominates disability in LCA, visual index scores used to calculate utility in these models could not employ the visual-acuity-based scores that have been rigorously validated in other areas of ophthalmology.130 Furthermore, given the rarity of LCA2, a one-time cost to treat all prevalent disease might represent approximately 1 billion USD in the 4 trillion USD United States healthcare sector. This, however, does not mean that insurance providers will be able to cover the associated costs, and there are many patients currently living without health insurance in the United States. Finally, economies of scale will continue to present hurdles for the future implementation of gene editing therapies, as scale-up of successful approaches for more prevalent disease, such as beta-thalassemia, that require viral vectors are estimated to cost millions of dollars per patient.131 Nonviral mediated gene delivery, such as the use of lipid nanoparticles, may provide reduced costs in the production pipeline.132
Estimation of total costs in patients with relapsed or refractory diffuse large B-cell lymphoma receiving tisagenlecleucel from a US hospital’s perspective
Published in Journal of Medical Economics, 2020
Hongbo Yang, Yanni Hao, Xinglei Chai, Cynthia Z. Qi, Eric Q. Wu
The cost proportion of the tisagenlecleucel procedure is generally consistent with the trend of other innovative cell and gene therapies, where the drug/procedure cost is the major component of the overall costs. The CAR-T procedure cost for axicabtagene ciloleucel is 71% of the total treatment cost for patients with B-cell lymphoma32, similar to the proportion of the treatment costs for AVXS-101 ($2.4–4.9 million [58%–73%] of $4.2–6.6 million total cost) and voretigene neparvovec ($850,000 [82%–88%] of 0.96–1.04 million total cost)33,34. Although the up-front costs of the tisagenlecleucel procedure are high, this can be potentially offset by the lower non-procedure costs. Indeed, a recent study by Kilgore et al. that used real-world data from 100% Medicare Fee-For-Service Part A and B claims reported that the HRU and total costs incurred by older patients with DLBCL (mean age: 70 years) decreased after CAR-T infusion31.