PTC Therapeutics Announces Interim Phase 2 Results
of PTC124 in Cystic Fibrosis
SOUTH PLAINFIELD, NJ - April 4, 2006 - PTC Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the discovery, development, and commercialization of orally administered, proprietary small-molecule drugs that target post-transcriptional control processes, today announced interim results from Phase 2 clinical trials of PTC124 in patients with cystic fibrosis (CF) due to a nonsense mutation. These interim data suggest that PTC124 may have pharmacological activity that addresses the underlying cause of CF in these patients.
PTC124 is an orally delivered investigational product candidate that PTC is developing for the treatment of genetic disorders due to nonsense mutations. Nonsense mutations are alterations in the genetic code that prematurely halt the translation process, producing a shortened, non-functional protein. Phase 2 clinical trials are ongoing in the two initial indications being pursued, CF and Duchenne muscular dystrophy (DMD) caused by nonsense mutations.
PTC is conducting two comparable Phase 2 clinical trials of PTC124 in CF, one at the Hadassah University Hospital in Jerusalem, Israel, and the other at four sites in the US (University of Alabama at Birmingham Hospital and Clinics, AL; Johns Hopkins Hospital, Baltimore, MD; Rainbow Babies' and Children's Hospital, Cleveland, OH; and Denver Children's Hospital, Denver, CO). In each study, patients receive two sequential two-week courses of treatment, first at a lower and then at a higher PTC124 dose level.
The primary endpoint of these trials is the change in the CFTR chloride channel activity (also known as chloride conductance). Chloride conductance is evaluated using a standardized nasal transepithelial potential difference (TEPD) procedure. Cystic fibrosis patients lack sufficient CFTR protein and therefore have an abnormal TEPD chloride conductance.
Fifteen patients have completed two cycles of treatment and data from these patients were available for inclusion in the interim analysis. Of these patients, three were from the U.S. trial and 12 were from the Israeli trial. All patients had a nonsense mutation and multiple signs and symptoms of CF, with most patients having lung dysfunction, chronic bacterial infection of the lungs, pancreatic insufficiency, and low body weights.
In these 15 patients, at both dose levels, statistically significant results were observed in all three ways in which the TEPD endpoint was assessed, including mean improvement in chloride conductance, percentage of patients with a chloride conductance response, and percentage of patients with a chloride conductance improvement into the normal range. Statistically significant improvements in other endpoints, including lung function and weight were also observed. Several patients also reported improvement in well-being, decrease in cough, decreased mucus thickness, and easier clearing of mucus.
"We believe that these results suggest that PTC124 has meaningful pharmacological activity that is consistent with our hypothesis that treatment with PTC124 can restore the production and function of CFTR protein in patients with cystic fibrosis caused by a nonsense mutation," said Stuart W. Peltz, Ph.D., President and Chief Executive Officer of PTC. "We also believe that this is the first time such activity has been observed in a clinical trial of an oral therapy for cystic fibrosis."
PTC124 was generally well tolerated among the 15 patients included in the interim analysis. All adverse events that were potentially drug-related were mild in severity; there were no safety concerns identified in patients' physical examinations, vital sign measurements, or electrocardiograms; and no meaningful changes in laboratory safety parameters were observed. There were no dosing interruptions or trial discontinuations due to toxicity. Evaluation of treatment compliance indicated that patients took more than 98% of the intended total drug treatment at both the lower and higher dose levels. Pharmacokinetic data indicated that PTC124 was readily absorbed and desired plasma concentrations were achieved and maintained at the first and fourteenth days of both the lower-dose and higher-dose treatment courses.
PTC's Phase 2 CF and DMD clinical trials are ongoing. The interim results do not necessarily predict favorable final results from these ongoing CF or DMD trials or any future trial.
About PTC Therapeutics, Inc.
PTC is a biopharmaceutical company focused on the discovery, development, and commercialization of orally administered, proprietary small-molecule drugs that target post-transcriptional control processes. Post-transcriptional control processes regulate the rate and timing of protein production and are of central importance to proper cellular function. PTC has assembled proprietary technologies and extensive knowledge of post-transcriptional control processes that it applies in its drug discovery and development activities. PTC's current pipeline of clinical and preclinical product candidates addresses multiple indications, including genetic disorders, oncology, and infectious diseases.
About PTC124
PTC124 is an orally delivered investigational product candidate in development 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. PTC124 has demonstrated activity in preclinical genetic disease models harboring nonsense mutations allowing the restoration of the production of full-length, functional proteins. In Phase 1 clinical trials, 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 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 13% of the cases of DMD are due to nonsense mutations. PTC believes that PTC124 is potentially applicable to a broad range of other genetic disorders in which a nonsense mutation is the cause of the disease. The FDA has granted PTC124 Fast-Track designations 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 Muscular Dystrophy Association (MDA), Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), 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 among the most common life-threatening genetic disorders worldwide. According to the Cystic Fibrosis Foundation, CF affects approximately 30,000 adults and children in the United States and, according to the European Cystic Fibrosis Foundation, it affects a similar number of patients in Europe. CF occurs in approximately one of every 3,500 live births, with approximately 1,000 new cases diagnosed each year in the United States. There is a commercially available genetic test to determine if a patient's CF is caused by a nonsense mutation and it is estimated that nonsense mutations are the cause of CF in approximately 10% of patients in the United States. There is currently no available therapy to correct defective CFTR production and function. Instead, available treatments for CF are designed to alleviate the symptoms of the disease. These treatments include chest physical therapy to clear the 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. In addition, the majority of cystic fibrosis patients take pancreatic enzyme supplements to assist with food absorption in digestion. There is a significant unmet medical need for a treatment for the underlying cause of CF. More information regarding CF is available through the Cystic Fibrosis Foundation (www.cff.org).
of PTC124 in Cystic Fibrosis
SOUTH PLAINFIELD, NJ - April 4, 2006 - PTC Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the discovery, development, and commercialization of orally administered, proprietary small-molecule drugs that target post-transcriptional control processes, today announced interim results from Phase 2 clinical trials of PTC124 in patients with cystic fibrosis (CF) due to a nonsense mutation. These interim data suggest that PTC124 may have pharmacological activity that addresses the underlying cause of CF in these patients.
PTC124 is an orally delivered investigational product candidate that PTC is developing for the treatment of genetic disorders due to nonsense mutations. Nonsense mutations are alterations in the genetic code that prematurely halt the translation process, producing a shortened, non-functional protein. Phase 2 clinical trials are ongoing in the two initial indications being pursued, CF and Duchenne muscular dystrophy (DMD) caused by nonsense mutations.
PTC is conducting two comparable Phase 2 clinical trials of PTC124 in CF, one at the Hadassah University Hospital in Jerusalem, Israel, and the other at four sites in the US (University of Alabama at Birmingham Hospital and Clinics, AL; Johns Hopkins Hospital, Baltimore, MD; Rainbow Babies' and Children's Hospital, Cleveland, OH; and Denver Children's Hospital, Denver, CO). In each study, patients receive two sequential two-week courses of treatment, first at a lower and then at a higher PTC124 dose level.
The primary endpoint of these trials is the change in the CFTR chloride channel activity (also known as chloride conductance). Chloride conductance is evaluated using a standardized nasal transepithelial potential difference (TEPD) procedure. Cystic fibrosis patients lack sufficient CFTR protein and therefore have an abnormal TEPD chloride conductance.
Fifteen patients have completed two cycles of treatment and data from these patients were available for inclusion in the interim analysis. Of these patients, three were from the U.S. trial and 12 were from the Israeli trial. All patients had a nonsense mutation and multiple signs and symptoms of CF, with most patients having lung dysfunction, chronic bacterial infection of the lungs, pancreatic insufficiency, and low body weights.
In these 15 patients, at both dose levels, statistically significant results were observed in all three ways in which the TEPD endpoint was assessed, including mean improvement in chloride conductance, percentage of patients with a chloride conductance response, and percentage of patients with a chloride conductance improvement into the normal range. Statistically significant improvements in other endpoints, including lung function and weight were also observed. Several patients also reported improvement in well-being, decrease in cough, decreased mucus thickness, and easier clearing of mucus.
"We believe that these results suggest that PTC124 has meaningful pharmacological activity that is consistent with our hypothesis that treatment with PTC124 can restore the production and function of CFTR protein in patients with cystic fibrosis caused by a nonsense mutation," said Stuart W. Peltz, Ph.D., President and Chief Executive Officer of PTC. "We also believe that this is the first time such activity has been observed in a clinical trial of an oral therapy for cystic fibrosis."
PTC124 was generally well tolerated among the 15 patients included in the interim analysis. All adverse events that were potentially drug-related were mild in severity; there were no safety concerns identified in patients' physical examinations, vital sign measurements, or electrocardiograms; and no meaningful changes in laboratory safety parameters were observed. There were no dosing interruptions or trial discontinuations due to toxicity. Evaluation of treatment compliance indicated that patients took more than 98% of the intended total drug treatment at both the lower and higher dose levels. Pharmacokinetic data indicated that PTC124 was readily absorbed and desired plasma concentrations were achieved and maintained at the first and fourteenth days of both the lower-dose and higher-dose treatment courses.
PTC's Phase 2 CF and DMD clinical trials are ongoing. The interim results do not necessarily predict favorable final results from these ongoing CF or DMD trials or any future trial.
About PTC Therapeutics, Inc.
PTC is a biopharmaceutical company focused on the discovery, development, and commercialization of orally administered, proprietary small-molecule drugs that target post-transcriptional control processes. Post-transcriptional control processes regulate the rate and timing of protein production and are of central importance to proper cellular function. PTC has assembled proprietary technologies and extensive knowledge of post-transcriptional control processes that it applies in its drug discovery and development activities. PTC's current pipeline of clinical and preclinical product candidates addresses multiple indications, including genetic disorders, oncology, and infectious diseases.
About PTC124
PTC124 is an orally delivered investigational product candidate in development 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. PTC124 has demonstrated activity in preclinical genetic disease models harboring nonsense mutations allowing the restoration of the production of full-length, functional proteins. In Phase 1 clinical trials, 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 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 13% of the cases of DMD are due to nonsense mutations. PTC believes that PTC124 is potentially applicable to a broad range of other genetic disorders in which a nonsense mutation is the cause of the disease. The FDA has granted PTC124 Fast-Track designations 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 Muscular Dystrophy Association (MDA), Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), 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 among the most common life-threatening genetic disorders worldwide. According to the Cystic Fibrosis Foundation, CF affects approximately 30,000 adults and children in the United States and, according to the European Cystic Fibrosis Foundation, it affects a similar number of patients in Europe. CF occurs in approximately one of every 3,500 live births, with approximately 1,000 new cases diagnosed each year in the United States. There is a commercially available genetic test to determine if a patient's CF is caused by a nonsense mutation and it is estimated that nonsense mutations are the cause of CF in approximately 10% of patients in the United States. There is currently no available therapy to correct defective CFTR production and function. Instead, available treatments for CF are designed to alleviate the symptoms of the disease. These treatments include chest physical therapy to clear the 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. In addition, the majority of cystic fibrosis patients take pancreatic enzyme supplements to assist with food absorption in digestion. There is a significant unmet medical need for a treatment for the underlying cause of CF. More information regarding CF is available through the Cystic Fibrosis Foundation (www.cff.org).