ProQR Therapeutics is set to release results from a study on the effect of the investigational drug QR-010 on nasal potential difference – an evaluation of CFTR protein function in patients with cystic fibrosis (CF).
The findings will be presented at the North American Cystic Fibrosis Conference (NACFC), Oct. 27 – 29, in Orlando, Florida. Preliminary data from a Phase 1b study exploring the safety and tolerability of QR-010 will also be presented at the meeting.
QR-010 is an RNA-based compound intended to correct the underlying cause of CF in patients with the ΔF508 mutation in the CFTR gene (CFTR is the gene defective in CF patients). The drug repairs messenger RNA (mRNA), the transcribed copy of a gene that is used as a blueprint for the corresponding protein.
The drug is administered by a nebulizer, which is a device that produces a fine mist inhaled into the lungs. Development is aided by an “orphan drug” designation in the United States and the European Union.
Simply, an “orphan drug” designation is given to an investigational therapy likely to treat an illness so rare that developing it for profit, or marketability, is not feasible. The drug is developed for public need rather than economic gain.
The two studies currently investigating QR-010 focus on different aspects of the drug development process.
The PQ-010-001 study exploring the safety and tolerability of the drug in a 28-day trial, is now enrolling patients at 22 centers across nine countries in North America and Europe. The study will randomize 64 patients carrying two copies of the ΔF508 mutation to receive either QR-010 or placebo in a double-blind fashion.
Patients will be exposed to increasing doses of the drug to determine a suitable dose range, and will inhale the drug three times a week. The study will also look at other factors linked to drug efficacy, such as measurements of sweat chloride, weight gain, respiratory symptom scores and lung function.
The other study, PQ-010-002, exploring the effect of the drug on nasal potential difference will also run for 28 days, with patients at five study centers across the U.S. and Europe. The recruitment plan seeks 16 patients; eight with two copies of the ΔF508 mutation, and eight with one gene affected by the ΔF508 mutation, and one gene affected by another CF causing mutation. If necessary, the study will enroll another 16 patients.
The nasal potential difference is a method to assess the function of the CFTR protein by measuring the transport of chloride ions in the outer cell layer inside the nose of patients with CF. If the drug is able to restore CFTR function in patients, as previously shown in mice, the study will prove that the drug’s repair mechanism is effective also in humans.
In a press release, Daniel de Boer, CEO of ProQR, said the company looks forward to announcing data so far from the two ongoing clinical studies of QR-010.
“The data from the NPD [nasal potential difference] trial could be a key validating proof-of-concept study informing us of the activity of QR-010 in CF patients. Releasing the preliminary single-dose results of our Phase 1b study at the same time marks a milestone in our clinical development program,” de Boer said. “In our pre-clinical models QR-010 showed an unprecedented restoration of CFTR function in the NPD test. Because NPD in CF patients has positive predictive value for clinical benefit, we would see a positive outcome in this study as an important proof of efficacy.”