RNA Therapies Emerge for Genetic Diseases


Applied Clinical Trials

Therapies aimed at correcting genes that cause diseases are gaining ground in biopharma, some are even specializing in specific mechanisms of action by targeting and modifying RNA through temporary and ongoing treatment. CEO at ProQR Therapeutics, Daniel de Boer, discusses how they are advancing RNA therapies in retinal disorders.

Therapies aimed at correcting genes that cause diseases are gaining ground in the biopharmaceutical industry. Some biopharmaceutical enterprises are even specializing in specific mechanisms of action by targeting and modifying RNA through temporary and ongoing treatment to avoid safety concerns that may arise from permanent gene therapy alterations. In this article, Daniel de Boer, CEO at ProQR Therapeutics, will discuss how they are advancing RNA therapies in retinal disorders.

Moe AlsumidaieWhat rare diseases do you aim to treat and how do you intend to treat them?

Daniel de Boer

Daniel de Boer: ProQR Therapeutics is a company focused on the development of RNA therapies for severe, genetic disease with a particular focus on genetic forms of blindness, also called inherited retinal diseases.
These are a group of diseases that, due to a genetic defect, lead to blindness somewhere over the course of a patient's life, depending on the type of genetic defect, that onset of blindness could be earlier or later in life.

RNA therapies are a group of genetic medicine that treats these diseases at the core, so it modifies the genetic defect, in this case in the RNA. Therefore, the defective protein is restored to normal, which could potentially reverse the disease.

For example, Leber’s congenital amaurosis type 10 (LCA10) is a very severe form of genetic blindness. There were patients in our trial who had been blind for twenty years and literally could not see anything. After just one dose of our drug, the defective protein was restored in their eyes, and these patients went from not being able to see anything to now being able to read, recognize people’s faces and lead an independent life.

In addition to our program for LCA10, we have clinical trials ongoing for RNA therapies in other inherited retinal diseases, including Usher syndrome and autosomal dominant retinitis pigmentosa (adRP).

MA: Why is RNA therapy better than other other approaches currently being explored for rare diseases?DB: We live in a fascinating time. There are a lot of different technologies being pursued to benefit patients who are in need of transformative therapies. Every technology has different advantages in specific areas. With respect to ProQR's technology and our RNA therapies, we believe we have an excellent application in the eye.

We see that RNA therapies in the eye are very stable, which allows us to dose just once or twice a year. We know that they distribute very well to all cells in the eye, which is not possible for most other technologies. We can, therefore, treat all areas of the retina, not just one specific spot, which is a typical disadvantage of other technologies aiming to treat these diseases. We think we have a very significant opportunity here. There are hundreds of genetic eye diseases that currently have no treatment. We think that with our technology, we can treat a significant part of those populations. 

MA: How do you design studies that are more patient-focused? Any challenges associated with these studies? DB: It is not easy to develop clinical trials and running clinical trials in orphan diseases are more challenging. In these small indications with less than thirty thousand patients in the world, little is known about the progression of the disease. There is also uncertainty about which endpoints are going to be most sensitive, about how patients will respond to experimental therapies and what their particular challenges will be in clinical trials. Clinical trials are a bit more difficult given that these types of rare diseases have not been widely studied before.

I think we had to do a lot of the leg work to get ready for that. ProQR is a very patient-focused company. We put patients at the center of everything and we design studies with the patient at heart. Before we start designing a study, we organize patient advisory boards where we invite patients, representatives of patients and organizations from all over the world to help us think through what is most important to them and what kinds of improvements would have the most impact on them on a personal level.

Subsequently, we look at ways we can capture those improvements. For example, we are developing endpoints for our genetic eye disease trials that allow us to measure how people can navigate through the real world. We call this a mobility test. We set up a mobility course at the trial sites and then we can measure at different light levels how patients navigate through because we know it is essential for patients to be independent.

MA:  Is there a realistic chance patients can see again or are these therapies more to improve vision?DB: One of the first patients in our LCA10 trial was a 40ish-year-old male. This gentleman lost his sight in his 20s and had been completely blind for about 15-20 years. The only thing he could see is if it was day or night, but he couldn't see movement, shape or color. This gentleman received one dose of our drug in one of his eyes. Six weeks later, he calls his physician and says, ‘I am walking through the airport and I can read signs.’ This gentleman went from seeing nothing to now being able to read and recognize people. We are not just hopeful, but we have seen real-life improvements. 

MA: How do you address safety issues?DB: We do a tremendous amount of pre-clinical safety studies to understand what we will potentially encounter and what we have to look for in a clinical setting. So far, these studies show to be really predictive, so that's very helpful. Then there is the reality that there are a limited number of patients with these diseases. It is helpful for us that RNA therapies in the eye are pretty well understood. From a safety perspective, they typically behave in the same way, and therefore we can build on a wealth of experience that is out there with RNA therapies in the eye to inform the safety of our programs.

MA: Is this a one-time administration of therapy?

DB: It is a chronic therapy that likely needs to be administered once or twice every year. It is not very frequent, so it is a low burden on patients. Physicians like to continue to see their patients and monitor their progression and make sure their patients are in good shape. From a patient perspective, receiving treatment once or twice a year to prevent blindness or maybe even improve vision is generally, and this is what we learn from patients, an acceptable burden. On top of that, there is probably a safety aspect to this. A drug that you give only once with permanent results may have irreversible safety outcomes that are permanent. In our situation, where we dose once or twice a year, if there would be a negative effect at some point in the future, you can always stop treating the patient and reverse the safety concern.


Moe Alsumidaie, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.

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