ProQR spotlights the most encouraging results from a mixed snapshot of efficacy for cystic fibrosis

Execs at ProQR Therapeutics $PRQR are doing their level best this afternoon to accentuate the positive in their early snapshot of the impact its lead RNA therapy has on cystic fibrosis. The big question is whether they can get investors to look past a slate of failed p-values in the Phase Ib — as well as the implications of some heavyweight competition — as they line up regulatory insights for the next big clinical development step.

To be sure, the per protocol data being trotted out this afternoon is divided among some tiny groups of patients divvied up between 4 dosing cohorts and a placebo arm. In the breakdown, QR-010 did achieve statistical significance for two of the overall cohorts in measuring the responses on symptoms from a patient questionnaire. But it also missed on the low and high doses.

The big issue will be FEV1, a crucial measure of lung function which is critical in cystic fibrosis studies. On the basis of FEV1, the drug missed 4 straight shots at statistical significance in tiny dosing groups of 5 or 6 patients, often badly. The high 50 mg dose tracked close to the placebo arm, with 8 patients. Only by moving to a subgroup of patients with lower lung function scores did researchers find one dose that hit the FEV1 mark with a 10.9% improvement.

Encouragingly, the same 12.5 mg dose arm in the subgroup also had the best response on symptoms: plus 27.5 compared to an 11.8 point drop in the placebo arm.

These data takes some explaining, CEO and company founder Daniel de Boer tells me.

The primary goals are safety and tolerability, he says, with a shot at some exploratory endpoints. In the upcoming Phase II study, they’ll move away from a population of patients with near normal levels of lung function — where it can be very difficult to track improvements of any kind — into patients where they saw the best responses in this small study.

“We’re excited,” says de Boer, who got started with the help of the late Henri Termeer. There was plenty of clinically meaningful data in the study to indicate the drug’s potential. And while the press will be on to meet with regulators on next steps, the Dutch biotech also plans to make sure they can move on Phase II relatively quickly, as rivals in the field add pressure to perform well as the landscape shifts.

Unlike the leader in CF — Vertex, which is pitching a combination of tezacaftor/ivacaftor that targets the F508del mutation to get the CFTR protein to the cell surface, where another drug amps its performance — ProQR tries to achieve its goal with an inhaled therapy that binds specifically to the defective CFTR RNA in order to correct the F508del mutation and restore the function of the CFTR protein, stopping disease progression.

Vertex has had some stellar data to report to regulators, and experience in a field that has delivered blockbuster expectations about its future. But de Boer says that he expects that ultimately there will be a variety of drugs on the CF market, with doctors and patients able to pick the one that will work best for them.

That’s a field he plans to be competitive in — provided the next round of efficacy data starts to look dramatically better.

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