Potential Cystic Fibrosis Treatment, Now in Phase 2 Study, Granted ‘Fast Track’ Designation by FDA

Nivalis Therapeutics, Inc., recently announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to its lead investigational drug, N91115, a stabilizer of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, as a potential treatment for patients with cystic fibrosis (CF). The drug is now being evaluated in a Phase 2 clinical trial.

“We are very pleased to announce the FDA’s Fast Track designation, as this status is intended to facilitate the development and expedite the review of important new treatments, like N91115, that stand to help people living with serious conditions like CF,” Jon Congleton, Nivalis’ president and CEO, said in a press release. “The Fast Track designation, coupled with the recent Orphan Drug designation from the FDA and initiation of a Phase 2 clinical trial of N91115, provides even more momentum in our work to address the significant unmet medical need that remains in the treatment of people with CF.”

CF develops due to a defect in the chloride channel CFTR, caused by mutations in the CFTR gene. Nivalis’ N91115 works through GSNOR inhibition, which is presumed to modulate the unstable and defective CFTR protein that is responsible for CF. According to the company, GSNOR inhibition restores endogenous S-nitrosoglutathione (GSNO) levels to modify the chaperones responsible for CFTR protein degradation. Its stabilizing effect increases and prolongs the function of the CFTR chloride channel, leading to an increase in net chloride secretion.

N91115 is now being evaluated for its safety and efficacy (NCT02589236) in adult CF patients who have two copies of the F508del mutation (a common CFTR mutation) and are being treated with lumacaftor/ivacaftor (Orkambi). Previous studies included a Phase 1a safety study in healthy volunteers, a Phase 1b safety study in CF patients with two copies of the F508del mutation, and preclinical studies in which N91115 proved to increase the function of F508del-CFTR.

The Phase 2 clinical trial, started in late 2015 with data expected in late 2016, is still recruiting patients at 45 centers across the U.S. More information is available for those interested through this clinical trials.gov link.

The Fast Track program facilitates the development and review of promising drugs intended to treat life-threatening diseases with unmet medical needs. The Orphan Drug program provides special status to drugs and biologics indicated for the treatment, diagnosis, or prevention of diseases that affect less than 200,000 individuals in the United States.