ProQR Warns of Clinical Delays Due to COVID-19 As it Reports Positive Interim Results for Rare Eye Disease Therapy

Rare Daily Staff

ProQR said it expects the COVID-19 pandemic to delay all of its ongoing and scheduled clinical trials as it released positive results from an interim analysis of phase 1/2 data for its RNA therapy QR-421a as a treatment for Usher Syndrome and non-syndromic retinitis pigmentosa.

ProQR is the latest of a growing list of drug companies to report that the COVID-19 pandemic is slowing the pace of clinical development. The company said severity and exact impact remains unknown.

To mitigate the impact, the company said that it is putting in place procedures that will allow a rapid ramp up in enrollment as soon as the disruption resolves, including additional patient identification activities and documentation for additional site activations.

For the trials of QR-421a and QR-1123, patients have already been identified for the next dose cohorts and the company expects to begin dosing as soon as practical after clinical sites are ready and able to do so. This will be the same for the start of the clinical trial for QR-504a. ProQR said it currently does not believe that its supply chain will be affected.

Due to the COVID-19-related delays, the company has also undertaken a budget review process, and expects its cash runway to extend into the second half of 2022.

“In these uncertain times, the health and safety of patients in our trials, their caregivers, and our employees remains our top priority. We believe we have taken appropriate measures designed to limit their risk,” said Daniel de Boer, CEO of ProQR. “While we manage the challenges stemming from the COVID-19 pandemic, we remain confident in the fundamentals of our business, as demonstrated in part by the data we are sharing today from our QR-421a program.”

Usher syndrome is the leading cause of combined deafness and blindness. Patients with this syndrome generally progress to a stage in which they have very limited central vision and moderate to severe deafness. Usher syndrome type 2 is one of the most common forms of Usher syndrome and is caused by mutations in the USH2A gene. To date, there are no approved treatments or products in clinical development that treat the vision loss associated with Usher syndrome type 2.

QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of vision loss in Usher syndrome type 2 and non-syndromic retinitis pigmentosa (RP) due to mutations in exon 13 of the USH2A gene. Mutations in this exon can cause loss of functional usherin protein that causes the disease. QR-421a is designed to exclude the genetic defect from the RNA in the eye, such that it leads to the expression of a shortened but functional usherin protein, thereby modifying the underlying disease. QR-421a has received orphan drug designation in the United States and the European Union.

As an RNA therapy, QR-421a targets the underlying cause of the genetic disease without the potential long-term side effects associated with targeting DNA. There are no approved therapies for Usher or nsRP.

The data from the three-month interim analysis of the QR-421a program showed that 25 percent of patients demonstrated benefit across multiple outcome measures in low- and mid-dose cohorts. These patients saw vision improvement in the treated eye of up to one line on a standard eye chart and either deterioration or no change in the untreated eye.

The company said the findings support continuing the trial as planned, with both cohort expansion and dose escalation in order to identify a potential development path to registration. ProQR plans to enroll additional patients for the mid-level dose cohort and dose escalate to the high-dose level in tandem.

Photo: Daniel de Boer, CEO of ProQR