Boulder, Colorado-based Nivalis Therapeutics recently announced the U.S. Food and Drug Administration (FDA) has granted the company’s lead clinical candidate, N91115, Orphan Drug Designation for the treatment of cystic fibrosis (CF). The designation gives Nivalis exclusive marketing for seven years against competition and includes incentives such as tax credits, federal grants, and a waiver of filing fees required under the Prescription Drug User Fee Act.
CF is a genetic disorder that, according to the Cystic Fibrosis Foundation, affects approximately 70,000 people worldwide, mostly in the U.S. and Europe. It is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR), which induces a dysfunction in the chloride channel.
While there is no cure for CF, several treatment methods are currently available, including drugs such as Orkambi; antibiotics to treat lung infections; chest physiotherapy for airway clearance; and surgery through lung transplantation in some severe cases. Each method has its own degree of success.
Nivalis’ drug candidate N91115 works through a new mechanism of action called S-nitrosoglutathione reductase (GSNOR) inhibition, which is believed to adjust the unstable and defective CFTR protein causing CF by restoring GSNO levels, as well as chloride secretion, in the lung mucus.
“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,” Jon Congleton, president and chief executive officer of Nivalis, 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.”
Orphan Drug Designation is generally granted by the FDA to drug candidates, many with limited profit potential, to treat rare conditions where there is an unmet need.
Nivalis has completed several clinical studies with N91115, including a Phase 1a dose-escalation safety study in healthy volunteers, and Phase 1b safety study in CF patients with two copies of the F508del mutation in CFTR. The results showed that N91115 is able to improve the proper function of the mutant protein F508del-CFTR, which is present in about 86 percent of CF patients.
Recently, Nivalis conducted a 12-week Phase 2 study to test the efficacy and safety of N91115, where 135 adult CF patients with F508del-CFTR mutation treated with Orkambi participated. The results will be announced in the second half of 2016.
Nivalis also plans to request FDA Fast Track Designation to advance the development of N91115. The company said it plans to use its proprietary GSNOR inhibitor portfolio to develop potential therapies for other disorders.