FDA Grants $1.6 Million for Investigational Cystic Fibrosis Drug

The FDA Office of Orphan Products Development has granted an award of approximately $1.6 million to PTC Therapeutics, Inc. (PTC) to support an ongoing Phase 3 study of ataluren in patients with nonsense mutation cystic fibrosis (nmCF).

The goal of the FDA’s OPD grant program is to support the clinical development of products for use in rare diseases or conditions where no current therapy exists or where the proposed product will be superior to the existing therapy. Cystic fibrosis (CF) is a life-threatening genetic disease that causes serious lung infections and digestive complications; according to the Cystic Fibrosis Foundation, the disease approximately 30,000 adults and children in the US and nearly 70,000 people worldwide.

“In addition to recognizing the potential of ataluren, this grant reflects PTC's long-standing commitment to developing new treatments for patients with rare genetic disorders that severely impact survival and quality of life,” said Stuart W. Peltz, PhD, president and CEO of PTC Therapeutics, in a statement.

The Phase 3 trial will enroll approximately 200 patients at research centers in North America, Europe and Israel. The primary goal of the study is to evaluate whether ataluren can improve lung function as measured by forced expiratory volume (FEV1). Other outcome measures will evaluate whether ataluren can decrease lung infections, reduce the frequency of cough and improve patient-reported quality of life. Patients are randomized to receive either ataluren (40 mg/kg) or placebo daily for 48 weeks. Study candidates will include patients who are at least six years of age and have CF due to a nonsense mutation.

Patients with CF lack adequate levels of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride channel necessary for normal function of the lung, pancreas, liver and other organs. In nmCF, an interruption in the genetic code—known as a nonsense mutation—prematurely halts the synthesis of CFTR, causing the protein to be short and non-functioning. Nonsense mutations are categorized as Class I mutations that result in little or no production of CFTR. CF patients with Class I mutations typically experience more severe disease symptoms than those with low-risk genotypes, including a greater than two-fold increased risk of death, a higher probability of end-stage lung disease and a higher prevalence of pancreatic insufficiency. Ataluren is designed to restore the missing CFTR. Through advances in genetic analysis, a test can now determine if a patient's disease is caused by a nonsense mutation.

According to the Cystic Fibrosis Foundation, it is estimated that nonsense mutations are the cause of CF in 10% of patients in the US and Europe and over 50% of patients in Israel. Available treatments for CF—which include chest physical therapy to clear thick mucus from the lungs, antibiotics to treat lung infections and a mucus-thinning drug designed to reduce the number of lung infections and improve lung function—are designed to alleviate symptoms rather than correct the underlying cause of the disease. In addition, the majority of cystic fibrosis patients take pancreatic enzyme supplements to assist with food absorption in digestion.

For more:

• Online CME—Optimizing Patient Outcomes: Clinical Use of the Cystic Fibrosis Pulmonary Guidelines
• CF Drug Development Pipeline
• Wall Street Journal—Inspire Pharma: Cystic Fibrosis Drug May Improve Lung Use