Luxturna: The latest development in gene therapy

Luxturna: The latest development in gene therapy

The development of gene therapies has been a long time coming, with many clinical failures until 2009 when successes brought a renewal of interest in gene therapy research.1 Since then, there have been advances made in using gene therapies to treat diseases, which has resulted in the production of a novel gene therapy. The gene therapy is voretigene neparvovec, more commonly known as Luxturna, which pending approval, will be the first to treat an inherited disease in the US.2 Although it is exciting to see gene therapies having success, the long-term outcome of these developments is still unknown.

Luxturna targets the RPE65 gene which, when mutated, causes diseases such as Leber Congenital Amaurosis-type 2 (LCA2).3 LCA is a rare genetic eye disorder which, depending on the type and severity can cause blindness. Specifically, LCA2 is caused by a recessive loss-of-function mutation, which makes it a good candidate for gene therapy.4 The recessive mutation only involves one gene and leaves the eye in good condition which allows this disease to be treated via gene therapy. The effects of LCA vary by individual, but generally include blindness at birth, crossed eyes, rapid involuntary eye movement, unusual sensitivity to light, clouding of the eyes and a cone shape to the front of the eye.3 The RPE65 gene product is produced in the retinal pigment epithelium (RPE) of the eye, but the mutation causes this gene product to be non-functional.5 The RPE gene product plays an important role in the visual cycle by converting the light entering the eye into electrical signals transmitted to the brain.5 By mapping the location of this gene, scientists were able to develop a gene therapy to treat LCA2.

“Luxturna studies have proved that it is an effective treatment option for a disease that currently has no treatments available.”

Studies have found that RPE65 mutations account for 16% of LCA cases, and because LCA patients retain normal retinal laminae and a definable photoreceptor layer into adulthood, LCA2 is a good target for gene therapy.4 In the development of the gene therapy, it was found that recombinant adeno-associated virus (rAAV) was the best vector for therapeutic gene delivery because it elicited the least severe immune response.4 In initial mice studies, gene therapy was effective, especially when treatment occurred at a younger age (1-2.5 months). Upon entering clinical trials, Luxturna also showed positive results with no serious side effects. In the Phase III trial to test the effectiveness of Luxturna, 65% of intervention patients were able to navigate a maze (used to assess mobility) at the lowest light level (lighting equivalent to a moonless night), demonstrating maximum improvement possible.6 Overall, the Luxturna studies have proved that it is an effective treatment option for a disease that currently has no treatments available.

The concept of using gene therapy to treat diseases first emerged in 1989 with the first approved human gene therapy trial.7 The study showed the feasibility and safety of using retroviral transduction for human gene therapy. Gene therapies have great potential in medicine because they could be able to treat many diseases that have always been thought of as untreatable. The number of clinical trials for gene therapies has increased fairly consistently since 1990.7 Reaching an all-time high in 2016 with 163 trials, most of which were conducted in the U.S., followed by the U.K., and Germany. Gene therapies in Canada accounted for only 1.11% of ongoing trials in 2016.7 Part of the reason for this is because of the strict guidelines for clinical testing of cell and gene therapy products, as well as reduced financial backing compared to the U.S.8 There aren’t any approved gene therapies in Canada, but there is one in the U.S. and three approved in the EU. Glybera was the first gene therapy approved in the EU in 2012, and its approval spurred an increase in clinical trials.7

“The majority of gene therapy studies (64.41%) are targeted for various types of cancer, some (9.90%) also aim to treat rare diseases which do not have existing cures.”

The discovery of the safety of gene therapies is exciting because unlike traditional therapies, which often aim to treat specific symptoms of a disease, gene therapy directly fixes the cause of the disease and associated symptoms. The majority of gene therapy studies (64.41%) are targeted for various types of cancer, some (9.90%) also aim to treat rare diseases which do not have existing cures.7 It is exciting that rare diseases are being targeted because rare diseases are often without any form of treatment and due to low incidence rates it can be difficult to get investors to fund research. The reason rare diseases such as Huntington’s disease, cystic fibrosis, Fanconi anemia, and Gaucher disease are targeted for gene therapy is that they are related to one single gene defect, so they can be treated genetically.7 Furthermore, because they are considered rare treatments, they can reach the market with lower requirements and higher prices, while being exempt from high taxation. Although it is good that these incentives exist for investors, it also makes the drugs more expensive for individuals requiring the treatment.

“When Glybera was released it cost €53,000 for one vial, resulting in a total cost of 1.11 million euros per patient.”

Even though the development of gene therapies for rare diseases is exciting it also comes at a cost. Performing research and developing these therapies is very expensive, which means when a product is successfully developed and approved it will also be very expensive for the patient. There are incentives for orphan drug developments established by the government such as tax exemptions which does not completely offset the price of treatment development.7 Often, big pharmaceutical companies will invest in a treatment, but that means that they also want a big pay off when the product is complete. When Glybera was released it cost €53,000 for one vial, resulting in a total cost of 1.11 million euros per patient.9

In order to make purchasing gene therapies feasible, there need to be proper funding models in place. Funding models need to be decided upon by the manufacturer and the buyer to ensure fair access to treatment while still generating profit.7 These models are known as managed entry agreements (MEAs), they often set a maximum price for the therapy and include financial schemes which can be performance-based for drugs with a high degree of uncertainty ineffectiveness.10 By developing effective MEAs, novel gene therapies can become accessible to all patients.

The advancement of gene therapies which provide treatment for diseases previously thought of as untreatable is an exciting advancement in medicine. This development is especially important for patients with rare diseases which have historically been neglected by pharmaceutical companies. Each year, as the number of clinical trials increases, it is more likely for there to be new treatments approved for rare diseases.

Works Cited:

1. Herzog R, Cao O, Srivastava A. Two Decades of Clinical Gene Therapy – Success Is Finally Mounting. Discovery medicine. 2010;9(45):105-111.

2. Taylor P. Spark Therapeutics’ Luxturna advisory committee vote sets gene therapy landmark. FierceBiotech. 2017. Available at:

3. Leber Congenital Amaurosis - NORD (National Organization for Rare Disorders). NORD (National Organization for Rare Disorders). 2017. Available at:

4. Cai X, Conley S, Naash M. RPE65: Role in the Visual Cycle, Human Retinal Disease, and Gene Therapy. Ophthalmic Genetics. 2009;30(2):57-62. doi:10.1080/13816810802626399.

5. RPE65 gene. Genetics Home Reference. 2017. Available at: Accessed November 4, 2017.

6. Russell S, Bennett J, Wellman J et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65 -mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. The Lancet. 2017;390(10097):849-860. doi:10.1016/s0140-6736(17)31868-8.

7. Hanna E, Rémuzat C, Auquier P, Toumi M. Gene therapies development: slow progress and promising prospect. Journal of Market Access & Health Policy. 2017;5(1):1265293. doi:10.1080/20016689.2017.1265293.

8. Ridgway A, Agbanyo F, Wang J, Rosu-Myles M. Regulatory Oversight of Cell and Gene Therapy Products in Canada. Advances in Experimental Medicine and Biology. 2015;871:49-71. doi:10.1007/978-3-319-18618-4_3.

9. Burger L. Exclusive: First gene therapy drug sets million-euro price record. Reuters. 2014. Available at:

10. Ferrario A, Kanavos P. Managed Entry Agreements For Pharmaceuticals: The European Experience. Brussels: EMiNet; 2013.

Cite This Article:

Smith E., Chan G., Palczewski K., Lewis K., Ho J. Luxturna: The latest development in gene therapy. Illustrated by L. Nguyen. Rare Disease Review. December 2018. DOI:10.13140/RG.2.2.32120.49924.

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