LCA Therapeutics

LCA Treatment

The potential of gene augmentation therapy for the treatment of IRDs is highlighted by the recent approval in the United States of voretigene neparvovec (tradename: Luxturna) for the treatment of RPE65 mutation-associated inherited retinal diseases.


Luxturna (voretigene neparvovec)

The first commercialized gene therapy for the treatment of an IRD, voretigene neparvovec (tradename: Luxturna, Spark Therapeutics), received approval from the United States Food and Drugs Administration (FDA) in December 2017. Luxturna is approved for use in children and adults who have vision loss due to inherited retinal diseases caused by mutations in both copies (bialleic) of the RPE65 gene and have sufficient viable retinal cells.

The RPE65 gene provides instructions for making an enzyme (a protein that facilitates chemical reactions) that is essential for normal vision. Mutations in the RPE65 gene lead to reduced or absent levels of RPE65 activity, blocking the visual cycle and resulting in impaired vision. Individuals with biallelic RPE65 mutation-associated retinal dystrophy experience progressive deterioration of vision over time. Mutations in RPE65 account for approximately 2% of cases of recessive retinitis pigmentosa and between 6–16% cases of Leber congenital amaurosis.

Luxturna works by delivering a normal copy of the RPE65 gene directly to retinal cells. These retinal cells then produce the normal protein that converts light to an electrical signal in the retina to restore patient’s vision loss. Luxturna is administered via subretinal injection in both eyes separately and on separate days. This procedure performed is a specialist eye surgeon. It is given as a one-time treatment.

The approval of Luxturna in the United States was based on the results of a clinical trial programme that enrolled a total 41 people between the ages of 4 and 44 years, all of whom had had confirmed biallelic RPE65 mutations. The effectiveness (efficacy) of Luxturna was demonstrated by a Phase 3 clinical trial that enrolled 31 participants. The study found that at 1 year after the treatment, participants who received Luxturna had significantly improved light sensitivity, visual fields, and navigational ability under dim lighting conditions, compared with the control group (participants who were not treated Luxturna). Furthermore, no product-related serious side effects were observed among patients treated with Luxturna during the study.

In Europe, Luxturna received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on 20 September 2018) who recommended granting of marketing authorisation. However, that is just one step on the road to access to treatments; the next hurdle is recommendation for reimbursement. This means that the treatment will need to be assessed via Health Technology Assessment (HTA) and other decision-making procedures in each country in order to be recommended to be made available in that country and for a price to be agreed with health care providers, public health systems or health insurance companies.

Future Prospects

While the gene therapy Luxturna has been recently approved by regulatory bodies, it is designed to treat only one subtype of LCA – people with specific biallelic mutations in the RPE65 gene. Other forms of LCA that are due to other gene mutations therefore would not benefit from Luxturna. However, the success of this first ocular gene therapy paves the way for other forms of inherited retinal disease to be treated with a similar technology of gene replacement.

Promising human clinical trials investigating an oral drug are also underway in forms of LCA caused by alterations in the RPE65 gene or the LRAT gene. These therapies aim to improve vision by bypassing the biochemical effects of lack of RPE65 or LRAT and thus “reawakening” dormant or sleeping retinal cells in order to allow the patient to see. It is extraordinary that this very uncommon, and severe, inherited retinal degeneration is the subject of several different clinical trials, which have shown early evidence of success. This gives justifiable hope that less severe inherited retinal degenerations might also be treatable in the foreseeable future.

Numerous clinical trials are currently evaluating the safety and effectiveness of gene therapy in several IRDs, including LCA, X-linked juvenile retinoschisis, RP, choroideremia, achromatopsia, and Leber Hereditary Optic Neuropathy.

You can find a list of current trials related to IRDs here. You can also find trials by searching on the website that lists most clinical trials, however it must be noted that not all trials listed on the website are valid or vetted. Therefore, we always advise that you talk with your ophthamologist about possible clinical trials participation.

While action is needed to maintain momentum in research and clinical trials to find these treatments, it is also of great importance to advocate for access to these treatments for all. Please see our Advocacy section for helpful information.

Access to Treatment

Luxturna has been approved as safe and effective by the American Food and Drug Administration (FDA) and is currently on the market in the USA. It was approved by the European Committee for Medicinal Products for Human Use (CHMP) in September 2018 and the European Medicines Agency (EMA) is expected to release its opinion by the end of 2018 on approval in Europe.Pending such approval,the next stages in the access journey will be at a local level where individual countries will decide whether to approve the therapy for reimbursement in their country. It is of utmost importance that patient groups in every country have the right information and the right advocacy tools to ensure that such life-changing treatments are made available in their countries.Information that would help illuminate the benefits of such a treatment includes:

  • the number of potential patients in each country, which requires access to genetic diagnosis. Please see our Red Alert Toolkit for more information(link)
  • the impact of these conditions on the life of the patients and of their families
  • the impact of these conditions on society, including the everyday care needs of someone with visual impairment from young children to adults; the potential effect on the education and employment of the patient and their carers; the additional supports supplied by health care providers, health systems or charity groups.

Retina International see the need for such information to be gathered and we are actively engaged in projects to this end. If you would like to contribute information of this kind, we would love to hear from you. Please get in touch and you can visit our section on Advocacy for more information on the need for data on impact.

While treatments such as gene replacement therapy are revolutionary, they are still quite a way from being universally available for all types of LCA. While we await new treatments, individuals with LCA and other IRDs can access appropriate visual supports to ensure they can live as fully and as independently as possible.

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