Gene therapy for RPE65 gene approved for use in EU

Posted on: Friday 23 November 2018

The gene therapy Luxturna has won European regulatory approval for the treatment of inherited retinal dystrophy caused by mutations in the RPE65 gene. This milestone decision was made by the European Medicines Agency (EMA) on Thursday, 22 November.

Luxturna is the first and only gene therapy available in Europe to treat inherited retinal disease. It had already been approved for use by the FDA in the United States.

There will now be significant discussions at national level to determine pricing and access to the treatment before it is made available to patients. The timeline for this is difficult to predict.

The RPE65 gene provides instructions for building an enzyme that is critical for recycling the substances that convert light into electrical signals at the back of the eye. If this enzyme is reduced or absent because of genetic mutations, the visual cycle is blocked, resulting in impaired vision and the accumulation of toxins.

Vision loss often starts during childhood or adolescence and progresses as retinal cells degenerate. Fifty percent of people with mutations in both their copies of the RPE65 gene (one copy is inherited from each parent) will experience severe sight loss by the time they are 16 years old.

The EMA has approved Luxturna for patients who have two mutated copies of RPE65 and still have sufficient viable retinal cells, as determined by an ophthalmologist, to benefit from the therapy. Luxturna works by delivering healthy, functional copies of the RPE65 gene, via a single retinal injection, to restore levels of the enzyme and allow the visual cycle to progress normally. As demonstrated in clinical trials, this can prevent further vision loss and can restore some functional vision; patients treated with Luxturna showed significantly improved night vision one year after treatment.

 “This is a milestone decision and one that provides huge hope for those who live with inherited retinal conditions,” said Tina Houlihan, Chief Executive of Retina UK. “We will now work with Novartis, the National Institute for Health and Care Excellence (NICE) and the NHS to ensure those who are able to benefit from this treatment have access to it as quickly as possible.”

Retina UK is a member of Retina International (RI), an umbrella organisation of more than 43 patient organisations worldwide promoting research to find treatments for inherited retinal degenerative diseases.

RI’s president, Christina Fasser, welcomed the news and added: “There is much work to be done before access to this potentially curative treatment is possible for eligible patients in Europe.

“Retina International asks those national agencies to understand that these conditions are degenerative and so time is of the essence in gaining access to treatment that can be life changing for those affected, their families and all those who care for them’.

Paul Hudson, CEO, Novartis Pharmaceuticals said: “Novartis is committed to working with patients, caregivers, health systems and physicians to establish access to this gene therapy for RPE65 patients, as we believe it can help restore sight and improve vision in children and adults who currently have no treatment options.”

Safety monitoring to continue
The most common side effects reported during clinical trials of Luxturna were eye redness, cataracts and increased ocular pressure. Although the EMA recommendation is based on a thorough review of the scientific data and a careful risk-benefit analysis, it does require long term follow up of treated patients to ensure continued safety and efficacy.

The treatment would need to be administered at an approved specialist centre.

About the manufacturer
Luxturna was developed and is made by US-based Spark Therapeutics but will be marketed here by Novartis.