PTC Therapeutics, Inc. Initiates Second Phase 2 Study Of PTC124 In Patients With Cystic Fibrosis In Israel

SOUTH PLAINFIELD, N.J., Dec. 22 /PRNewswire/ -- PTC Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the discovery, development, and commercialization of small-molecule drugs targeting post-transcriptional control mechanisms, today announced the initiation of a Phase 2 study of PTC124 at Hadassah University Hospital in Israel in patients with cystic fibrosis (CF) due to a nonsense mutation. This study is being conducted in parallel with a similar U.S.-based Phase 2 clinical trial in CF, which recently began recruiting patients.

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PTC initiated the Israeli study in collaboration with Dr. Eitan Kerem and Dr. Michael Wilschanski who had previously conducted an important proof-of- concept clinical trial using local application of gentamicin, an aminoglycoside antibiotic, to the nasal mucosa of patients with nonsense- mutation-mediated CF. That study was published in the October 9, 2003 issue of The New England Journal of Medicine, and demonstrated that gentamicin could overcome the effect of the nonsense mutation and induce production of full- length, functional CFTR protein in the nasal mucosal cells. However, the investigators concluded that the long-term use of gentamicin for this purpose is limited by the need for intravenous administration and its potential for serious renal and otic toxicities. PTC124 is an orally bioavailable new chemical entity unrelated to gentamicin that was specifically designed to induce production of full-length protein in genetic disorders due to a nonsense mutation.

"In studying the efficacy of locally applied gentamicin in patients with CF, we were excited by the positive data, but knew that it would not be able to provide a long-term treatment option," commented Dr. Michael Wilschanski, Director, Pediatric Gastroenterology at Hadassah University Hospital. Dr. Eitan Kerem, Head, Department of Pediatrics and CF Center, Hadassah University Hospital remarked "PTC124 offers the potential of a potent, easy-to-deliver oral therapy for patients with CF due to a nonsense mutation, but without the toxicity of aminoglycoside antibiotics. We are delighted to have the opportunity to conduct studies of this promising new drug."

PTC124 is being investigated initially as a treatment for CF and Duchenne muscular dystrophy (DMD), but also has the potential to treat a number of other genetic disorders. It is estimated that, worldwide, approximately 10% of patients with CF and 15% of patients with DMD have these disorders because of a nonsense mutation. However, in Israel, it is estimated that over 60% of patients with CF have the disease due to a nonsense mutation.

As in the U.S. Phase 2 study in CF, the Israeli study is enrolling patients who have undergone genetic testing to determine that they have CF due to the presence of a nonsense mutation in the CFTR gene. The primary endpoint is assessment of nasal transepithelial potential difference (NPD or TEPD) as a measure of CFTR function in response to treatment with PTC124. Secondary assessments of CFTR function also include mRNA, immunofluorescence, sweat chloride and pulmonary function tests. Safety, pharmacokinetics and compliance studies will also be performed.

"The pioneering work of Dr. Kerem and Dr. Wilschanski has set the foundation for the PTC124 clinical trials program. The patient care expertise and research experience of these investigators will be extremely beneficial as we continue to evaluate PTC124 clinically," stated Langdon Miller, M.D., Chief Medical Officer of PTC.

Stuart Peltz, Ph.D., PTC's President and Chief Executive Officer, added, "The involvement of these two thought-leaders in the development of PTC124 is a wonderful endorsement of our science. Their participation will enhance our understanding of PTC124's efficacy, safety, and pharmacology, and will add to our efforts to improve outcomes for patients with CF and other debilitating genetic disorders."

More information on the enrollment criteria and design of the Phase 2 clinical trials in Israel and the U.S. can be found at . A Phase 2 study of PTC124 in patients with DMD will also be initiated before the end of the year in the U.S.

About PTC Therapeutics, Inc.

PTC is a biopharmaceutical company focused on the discovery, development, and commercialization of small-molecule drugs targeting post-transcriptional control mechanisms. Post-transcriptional control processes are the sequence of events in the cell that ultimately regulate the rate and timing of all protein production. PTC discovers and develops small molecule drugs that alter these processes by selectively modulating how RNA is used to produce proteins. This approach enables PTC to advance its drug discovery programs rapidly from targets to preclinical and clinical drug candidates, building a pipeline across genetic disorders, oncology, and infectious diseases.

About PTC124

PTC124 represents a first-in-class, orally delivered investigational new drug for the treatment of genetic disorders due to nonsense mutations. Nonsense mutations are single-point alterations in the genetic code that prematurely halt the translation process, producing a shortened, non- functional protein. In pre-clinical trials, PTC124 allowed the cellular machinery to bypass the nonsense mutation, continue the translation process, and thereby restore the production of a full-length, functional protein. PTC124 has demonstrated the ability to restore full-length functional protein in preclinical genetic disease models harboring nonsense mutations. In Phase 1 clinical studies, PTC124 was generally well tolerated, achieved target plasma concentrations that have been associated with activity in preclinical models, and did not induce ribosomal readthrough of normal stop codons. Pharmacokinetic modeling of the Phase 1 results has allowed development of a dosing regimen for the Phase 2 studies in cystic fibrosis (CF) and Duchenne muscular dystrophy (DMD). It is estimated that 10% of the cases of CF and 15% of the cases of DMD are due to nonsense mutations. In addition to CF and DMD, other potential indications include hemophilia, neurofibromatosis, retinitis pigmentosa, epidermolysis bullosa, and lysosomal storage disorders. PTC124 may represent a unique opportunity to use a single small-molecule drug to address chronic and life-threatening diseases of high unmet medical need. The FDA has granted PTC124 fast-track designation for the treatment of CF and orphan drug designations for the treatment of CF and DMD due to nonsense mutations. PTC124 has also been granted orphan drug status for the treatment of DMD and CF by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMEA). PTC124's development is supported by grants from the Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), Muscular Dystrophy Association (MDA), FDA's Office of Orphan Products Development (OOPD), and by General Clinical Research Center grants from the National Center for Research Resources (NCRR).

About Cystic Fibrosis (CF)

CF is a life-threatening, genetic disease affecting approximately 70,000 people worldwide. A defective gene coding the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes the body to produce abnormally thick, sticky mucus that leads to chronic lung-infections and impairs digestion. It is estimated that approximately ten percent of CF patients have the disease due to a nonsense mutation. More information regarding CF is available through the Cystic Fibrosis Foundation ( ).

Photo: NewsCom: Therapeutics, Inc.

CONTACT: for Investors & media: Emily S. Poe of Noonan Russo for PTCTherapeutics, Inc., +1-212-845-4266,; or Jane Baj,+1-908-222-7000 ext. 167,, or for Patients, Patients'Families, Investigators and Patient Organizations: Kerri Donnelly,+1-908-222-7000 ext. 112,, both of PTC Therapeutics,Inc.

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