Researchers saw the biggest improvements in patients with a lower lung function at the beginning of the study, which only targeted patients with the F508del mutation.
“QR-010 exceeded expectations in this study as an innovative investigational therapy for the treatment of cystic fibrosis for which the need remains high,” J. Stuart Elborn, the study’s principal investigator clinical chair in respiratory medicine at Imperial College London, said in a press release. Elborn is also a consultant at England’s Royal Brompton Hospital and past president of the European Cystic Fibrosis Society.
QR-010 is an RNA-based drug engineered to bind to mutated CFTR messenger RNA (an intermediate between gene and protein) to restore its function.
The trial (NCT02564354) randomly assigned patients with two F508del mutations to one of four doses of QR-010 or a placebo. The trial included four single-dose and four multiple-dose groups.
In three out of four multiple-dose groups, researchers observed an average improvement of 13.0 to 19.2 points — using the Cystic Fibrosis Questionnaire-Revised Respiratory Symptoms Scale (CFQ-R RSS) — compared to placebo. Those with a lower lung function, however, improved by an average 27.5 points.
Researchers judge a 4.0 point improvement to be clinically meaningful.
Meanwhile, the study also measured lung function using percent predicted forced expiratory volume in one second (ppFEV). QR-010 improved lung function by 4.0 percent, which they considered a positive trend. In those with poorer lung function from the outset, the difference was 10.9 percent.
“The results of this Phase 1b trial support QR-010’s potential to be a meaningful therapy for people with cystic fibrosis,” said Daniel A. de Boer, ProQR’s CEO. “With these results in hand, we are designing a path forward for the development of QR-010, either independently or with a potential partner.”
The Dutch pharmaceutical company partnered with Cystic Fibrosis Foundation Therapeutics (CFFT) in 2014 to develop QR-010. CFFT, which is based in Bethesda, Maryland, initially said it would support the Phase 1b study and a proof-of-concept study of nasal potential difference — a common CF test.
But the positive data prompted CFFT to expand the partnership, which will now include inhaled RNA drugs for Class I — also called stop-codon — mutations in the CFTR protein. These mutations are not amenable to treatment with small molecule correctors; such patients have a continuously high unmet need for new treatments.
“The improvements demonstrated in reduction of respiratory symptoms are very encouraging and intriguing and of course of enormous importance to people with CF,” Elborn said. “The results of this study together with the previous proof of concept study are strongly supportive of the further development of QR-010.”
ProQR will report the full trial data at the Nov. 2-4 North American CF Conference (NACFC) in Indianapolis.