The US Food and Drug Administration (FDA) has granted orphan-drug designation to Genoa Pharmaceuticals' for the use of pirfenidone in their lead programme - inhaled GP-101 for the treatment of idiopathic pulmonary fibrosis (IPF).

"Acquiring orphan status marks an important regulatory milestone in GP-101's life cycle to treat people with this devastating disease," said Mark Surber, Genoa's president and chief executive officer. "We are pleased to continue the development of inhaled GP-101, with clinical trials beginning in early 2015."

Oral pirfenidone (Esbriet) has shown promise to slow IPF disease progression. Unfortunately, a very large oral dose is required to achieve efficacious lung levels. Despite being established at the upper safety threshold (801 mg TID), the resulting oral-delivered lung dose is too low for optimal effect. Moreover, gastrointestinal exposure and large-associated blood levels remain poorly tolerated. For these reasons oral-dose escalation for optimal IPF efficacy is not possible. Complicating matters, dose-absorbing food, first-pass metabolism, and safety-driven dose-reduction and stoppage protocols further reduce lung dose and interrupt maintenance therapy.

To address oral shortcomings and maximize IPF efficacy, Genoa has reformulated pirfenidone for aerosol formation and inhaled, direct-lung delivery (GP-101).  By this approach, ~160-fold less inhaled pirfenidone is predicted to deliver Esbriet-equivalent IPF efficacy (5 mg vs. 801 mg). With such a small inhaled dose, remaining safety and tolerability concerns may be eliminated, enabling improved patient compliance and an increased inhaled dose for superior IPF efficacy. In addition to serving as an improved-effect Esbriet replacement, a safe and well-tolerated inhaled product is expected to enable desired, but otherwise poorly-tolerated combination regimens (e.g., with Boehringer Ingelheim's Nintedanib).

Orphan drug designation is a status assigned to a medicine intended for use in rare diseases. In the US, the Orphan Drug Designation programme provides orphan status to medicines intended for the safe and effective treatment or prevention of rare diseases that affect fewer than 200,000 people. In the EU, a medicine must meet similar criteria, affecting up to five in 10,000 people. Orphan designation for inhaled GP-101 will be pursued in the EU with clinical data.  Orphan status provides sponsors with development and commercial incentives, including 7 and 10 years market exclusivity for these two regions, respectively.

IPF is a fatal lung disease caused by both genetic and environmental factors resulting in progressive lung scarring and death due to respiratory failure and/or co-morbidities.  Characterized by a dry cough, shortness of breath and decreased exercise capacity, this disease exhibits a post-diagnosis survival period of ~2-5 years, annually killing more people than breast cancer. As fibrosis is at present irreversible, an efficacious product will provide a well-tolerated stand-alone or combination maintenance therapy that protects healthy lung tissue against invading fibrosis or meaningfully slows disease progression.

Genoa Pharmaceuticals, Inc. is committed to developing improved therapies for the treatment of IPF. Based in San Diego, Genoa's lead program, GP-101 (aerosol pirfenidone) plans to enter clinical trials in early 2015.