With the December 2017 announcement that the world’s first ocular gene therapy had received approval by the U. S. Food and Drug Administration (FDA), there’s no doubt that 2017 was a landmark year for gene therapy. Looking back, 2017 was a year of firsts, including the first stem cell therapy clinical trial for macular degeneration involving reprogrammed donor stem cells, the first Clinician-Scientist Emerging Leader recipient, and the first year of the Foundation Fighting Blindness’s (FFB) new initiative, Restore Vision 20/20. Some of these highlights are featured in our 2017 impact report, which you can download here.
At the FFB, we are always looking forward to find the best ways to drive the development of sight-saving treatments. Here are the four emerging treatments and vision research trends that we’ll be following over the course of 2018:
- 1) Making Gene Therapy Accessible
We finished 2017 celebrating Luxturna: the world’s first ocular gene therapy to receive FDA approval! This means that the Luxturna gene therapy, which treats retinal dystrophies caused by biallelic RPE65 mutations, is no longer considered an experimental treatment – it’s an official treatment that has passed all of the scientific and regulatory milestones. Actually, this breakthrough was even more significant because Luxturna is the world’s first gene therapy to receive approval that targets a genetic disease caused by mutations in a specific gene – thereby paving the way forward for personalized medicine.
Since 2015, we have been closely following the development of Luxturna. You can read earlier stories about its development here. Over the years, we’ve learned a lot about the time and resources that are required to develop new drugs. The incredible monetary cost of drug development is well known, but it is also important to realize the tremendous resources that are needed to navigate the regulatory landscape. We always want things to move as fast as possible, but it is essential to respect that marshaling the first gene therapy through these processes has posed unique challenges. Pioneering a new path forward requires determination and creativity.
In Canada, we’re not there yet, because these regulatory processes are unique to each country. At the FFB, we are committed to working for our community to ensure that innovative sight-saving treatments are accessible to Canadians. As a start, we are in close communication with staff at Spark Therapeutics and with regulatory experts and ophthalmologists across Canada to learn how we can create the path forward in Canada.
2) More Clinical Trials
The number of clinical trials that are underway for people living with inherited retinal disease (IRDs) and age-related macular degeneration (AMD) continues to grow steadily. This trend will continue and gain momentum in 2018. At the FFB, we are committed to developing more resources that can help to connect you with relevant clinical trials and keep you up-to-date!
If you want more clinical trials and new treatments to come to Canada – sign up on FFB-Canada’s Patient Registry. The Patient Registry is an essential tool that was carefully designed to connect people living with an IRD to relevant clinical trials. By enrolling on the Patient Registry you help us to show that there are people in Canada who are interested in clinical trials and who need new treatments. It is free for you to sign up and it does not commit you to enrol in any trial. We don’t yet have a similar database for people living with AMD, but if you have AMD and are interested in clinical trials, please send us an email to let us know.
3) Better Together: Combination Therapies
Not too long ago, learning that you had age-related macular degeneration (AMD) was devastating. Nothing could be done to prevent vision loss. Over the past decade, anti-VEGF treatments, such as Lucentis, Eylea and Avastin, revolutionized the treatment of wet AMD. These drugs work in the eye by seeking out and blocking the action of a molecule known as vascular endothelial growth factor (VEGF). VEGF causes AMD by instigating the growth of abnormal, “leaky” blood vessels under the retina which leak fluid, obscuring central vision.
Although anti-VEGF therapies are very effective, there is still room for improvement! FFB-funded scientists, such as Dr. Andras Nagy, and industry experts have been steadily working to develop novel treatments with the potential to be even better than existing anti-VEGFs. The excellent efficacy of anti-VEGFs, however, means that it has been challenging to develop something better. In 2017, for example, we were watching the development of Bayer and Regeneron’s angiopoeietin2 (Ang2) antibody, which was designed to be delivered in combination with their existing anti-VEGF drug, Eylea. In late 2017, the phase 2 study demonstrated that delivering the two drugs in combination did not offer significant improvement over delivering Eylea alone. Despite this setback, we predict that we will continue to see more efforts to develop “combination approaches” that build on the success of anti-VEGF drugs by delivering them in conjunction with another medication.
4) From CRISPR to ASOs: Multiple Forms of Gene Editing to Treat Blindness
Last year we talked a lot about CRISPR, a precise gene-editing technology that simplifies the process of editing DNA, much in the same way that a word processor simplifies the process of editing a document. New companies, such as Editas Medicine, are working on two novel treatments that use CRISPR gene editing to fix the mutations that cause Leber Congenital Amaurosis (LCA) 10 and Usher Syndrome 2a. While this therapeutic approach is not yet as advanced as traditional gene therapy, which treats genetic diseases by introducing a new functional copy of a gene into the cells where it is needed, we expect that it will continue to advance in 2018.
In addition to using CRISPR to edit the DNA sequence of diseased-cells, we will be watching the development of ASO-based treatments (ASO = antisense oligonucleotides), which also use a gene-editing approach to treat disease. Instead of changing the DNA sequence, like CRISPR, ASO-based treatments work by repairing the genetic defect in the RNA. (We won’t explain the detailed differences between DNA and RNA here – stay tuned for a biology tutorial later!) What you need to know is that ASO treatments work by repairing RNA sequences so that normal protein function can be restored. Currently, the biotechnology company, ProQR, is testing an ASO-based therapy for LCA 10 in a clinical trial and has plans to develop treatments for other IRDs. The era of personalized medicine is just beginning!