Phase 2a clinical trial in nonsense mutation hemophilia A and hemophilia B initiated

PTC Therapeutics, Inc. (PTC) today announced it is expanding the development of ataluren, an investigational new drug, to a third indication with the initiation of a Phase 2a clinical trial in nonsense mutation hemophilia A (nmHA) and hemophilia B (nmHB). Hemophilia is a rare and debilitating genetic disorder that causes loss of blot clotting proteins and can lead to serious, recurrent bleeding episodes. It is estimated that nonsense mutations account for about 10 to 30 percent of all hemophilia cases.

The purpose of this multi-center, open-label trial is to evaluate the activity, safety, and pharmacokinetics of ataluren in approximately 24 adult male patients with nmHA or nmHB. The primary goal of the trial, which consists of two 14-day treatments at two different dose levels, is to determine if ataluren can safely increase FVIII and FIX activity levels.

"We are excited about the initiation of this proof-of-concept trial of ataluren in patients with nonsense mutation hemophilia, a more severe form of the disorder with a great need for alternative treatment options," said Langdon Miller, M.D., Chief Medical Officer of PTC Therapeutics. "The data from this study will add to the growing body of data that we are compiling with our ongoing studies in Duchenne/Becker muscular dystrophy and cystic fibrosis."

Patients with hemophilia A and B lack adequate levels of Factor VIII (FVIII) or Factor IX (FIX) proteins due to mutations in their genetic code. The lack of FVIII and FIX proteins leads to improper blood clotting and excessive bleeding. In nmHA and nmHB, an interruption in the genetic code - called a nonsense mutation- prematurely halts the synthesis of FVIII and FIX, causing the protein to be short and non-functioning. A genetic test is required to determine if a patient's disease is caused by a nonsense mutation. Patients with nmHA or nmHB typically produce little or no functional FVIII or FIX (less than one percent of normal plasma levels) and experience more severe symptoms than patients whose disease is caused by other mutations. Such low levels can result in spontaneous bleeding episodes that cause destruction of the joints, damage to other tissues and increased risk for intracranial bleeding, or bleeding into the brain, which may cause severe neurological symptoms, including stroke. Current therapies require repeated, frequent intravenous infusions to maintain FVIII or FIX levels. Ataluren administered orally is designed to address the underlying cause of nmHA and nmHB by promoting restoration of functional FVIII and FIX enzymatic protein.

"We are very pleased to be part of this groundbreaking trial," stated Kathy High, M.D., principal investigator at The Children's Hospital of Philadelphia. "HA and HB are chronic, disabling and potentially life-threatening genetic disorders, and there is a significant need for new strategies for preventing bleeding complications. For patients with nonsense mutation hemophilia, even a small increase in FVIII or FIX could be very beneficial. As an oral therapy, ataluren has the potential to offer a noninvasive treatment option."

"This proof-of-concept trial in a third indication represents a major step forward in the development of ataluren as a potential treatment for nonsense mutation genetic disorders," stated Stuart W. Peltz, M.D., president and CEO of PTC Therapeutics. "We are excited by the clinical progression of ataluren. We recently initiated a pivotal trial in nonsense mutation cystic fibrosis and expect to complete the pivotal trial in nonsense mutation Duchenne and Becker muscular dystrophy by the end of the year with results expected to be announced in the first half of 2010."