Rare Disease Report

Daniel de Boer, CEO of ProQR, Explains RNA Treatment, QR-313, for DEB

MAY 25, 2018
Krista Rossi
In a recent interview with Daniel de Boer, CEO of ProQR, Rare Disease Report ® discussed the company’s new RNA therapy, QR-313, for the treatment of dystrophic epidermolysis bullosa (DEB).

DEB, a debilitating genetic condition, causes the skin to be very fragile and blister easily—even from the slightest of injuries, such as bumping or rubbing. The disease is caused by a mutation in the gene called COL7A1, which, when mutated, doesn’t produce the required protein collagen VII necessary to create the anchoring fibers that hold the skin together.

The National Institutes of Health estimates that the incidence of all types of DEB is 6.5 per million newborns in the United States.

Rare Disease Report® (RDR®): Could you explain how QR-313 works for the treatment of dystrophic epidermolysis bullosa (DEB) and how it could significantly impact this patient population?

Boer: Dystrophic epidermolysis bullosa is the most severe form of epidermolysis bullosa. It is a skin disease where patients have blistering from birth and usually develop large, open wounds that don’t really close. These wounds lead to a very poor quality of life, and the life expectancy is low. These patients require very significant care for their entire lives, and today, there is no treatment options for these patients; they typically die before the age of 35.

We are hoping we can change that with the drug QR-313 that we are developing right now. QR-313 is a new therapeutic that is investigational and in clinical studies. It aims to restore normal skin in patients by closing the wounds and restoring normal skin strength. We are developing a so-called oligonucleotide, an RNA therapy; this oligonucleotide is topically applied. It is, basically, a cream that patients put on the skin. Our drug is formulated in that cream, and then the drug gets taken up into the skin where it targets the underlying genetic defect at the RNA level with the goal of restoring normal protein expression, with the goal of restoring normal, intact skin.

RDR®: Would you classify this as a gene therapy?

Boer: This is not gene therapy; this is RNA therapy. It’s a genetic therapy, but it is not a gene therapy. An RNA therapy has temporary effect, and gene therapy has a permanent effect. Both of those classes of therapies come with their own pros and cons. We think, bottom line, that this is a very elegant way to treat the underlying defects in these patients, and we think this provides a real treatment option for these patients.

RDR®: Do you see clinical trials coming in 2018? If so, when would you anticipate seeing these trials begin?

Boer: At ProQR, we are broadly focused on the development of therapies for genetic rare diseases. We are currently in a clinical study for a disease called Leber’s congenital amaurosis, which is a genetic form of blindness. Any day now, we expect to start a clinical study for the program we are talking about now for dystrophic epidermolysis bullosa and the QR-313 product. In this trial, we have completed all the necessary preparations needed. The study will start any day, and we will start dosing patients somewhere within the next 2 months. In this trial, we expect to dose somewhere between 4 and 15 patients. From those patients, we hope to establish that QR-313 restores normal protein expression and helps these patients close their wounds and keeps their wounds closed. The patients in this trial are patients that have this specific form of DEB, which are the patients who have a genetic mutation in exon 73. This genetically defines the subpopulation of dystrophic epidermolysis bullosa.

RDR®: Consequently, you’re anticipating beginning enrollment with some DEB patients?

Boer: Yes, any day now we expect to begin enrollment, and we anticipate to have the first clinical data readout in the second half of this year. That will be when 8 patients have completed their treatment period. We will have a second readout in the clinical trial after the follow-up period, which will be in 2019.

RDR®: How do you think QR-313, an RNA therapy, may work better than a gene therapy for DEB patients?  
        
Boer: The reason we are so excited about this technology is that it micro-surgically modifies the patient’s own RNA, and with that modification, it makes normal proteins. We leave the entire cell’s own regulating system in place. We only give the body the information to make a functional COL7A1 protein, which is the protein affected in these patients. The way that we do that is with proven technology that is broadly used and we think that it can provide a very meaningful treatment option for these patients. It is not invasive, they can use it at home, and it can hopefully help them restore normal, intact skin.

I think what’s also interesting and what we presented at the TIDES: Oligonucleotide and Peptide Therapeutics Conference in Boston Massachusetts, is that QR-313, preclinically, has shown to be efficacious, and not only by us, but also by independent academic groups that work with this approach to target exon 73. In both cellular models and en vivo models, this approach has shown to restore normal COL7A1 function in these models. That builds a lot of confidence going into this trial.

With respect to the trial, this is a very severe disease, and we are committed to making a difference for these patients. We certainly hope this early trial that we are starting will show us that these patients improved their skin strength after treatment with this therapeutic opportunity.

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