Cystic Fibrosis Drug Candidate Receives Orphan Drug Status From FDA

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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Nivalis Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted its lead investigational drug, N91115, orphan drug status for the treatment of cystic fibrosis (CF). Drug candidate N91115 is a stabilizer of the CF transmembrane conductance regulator (CFTR) protein.

Orphan drugs are generally those with a limited profit potential which are developed to meet an unmet need to treat rare conditions — hence the special designation from the FDA, which can make it easier to gain marketing approval.

A genetic disease, cystic fibrosis is the result of a defect in the chloride channel CFTR, caused by mutations in the CFTR gene. Investigational drug N91115 uses a novel mechanism of action — the inhibition of S-nitrosoglutathione reductase (GSNOR) — which has been presumed to modulate the unstable CFTR protein. This inhibition mechanism restores GSNO levels, producing a stabilizing effect that increases and prolongs CFTR chloride channel function and increases net chloride secretion.

Early clinical studies on N91115 are now concluded, including a Phase 1a dose-escalation safety study in healthy volunteers, and a Phase 1b study in CF patients with two copies of the F508del mutation in CFTR. In both studies, the CFTR stabilizer has been shown to increase the function of F508del-CFTR, the mutant protein estimated to exist in 86 percent of CF patients worldwide.

The company recently initiated a Phase 2 clinical trial (NCT02589236) to assess the efficacy and safety of drug candidate N91115 in 135 adult CF patients who are homozygous for the F508del-CFTR mutation and under treatment with the drug Orkambi. Results of this randomized double-blind, placebo-controlled, 12-week trial are expected in the second half of 2016.

The FDA Orphan Drug Designation program provides a special status to drugs and biologics intended to treat, diagnose or prevent diseases and disorders that affect fewer than 200,000 people in the U.S. The company also announced it will seek FDA fast-track status for its development program on N91115. Fast-track enables closer communication with the FDA to expedite the review process of drugs targeting serious or life-threatening diseases with the potential to address unmet medical needs.

“The orphan drug designation represents an important milestone in the development and regulatory strategy for N91115 and underscores the unmet need that remains in treating CF,” Nivalis President and CEO Jon Congleton said in a press release. “We look forward to the continued clinical advancement of this first-in-class CFTR stabilizer, a new approach to modulating the defective CFTR protein.”

According to the Cystic Fibrosis Foundation, CF is a severe genetic disease estimated to affect nearly 70,000 people worldwide, but predominantly in the U.S. and Europe.