Ataluren is an investigational (experimental) drug, which means it is being tested as a potential treatment and it has not yet been approved for sale by the U.S. Food and Drug Administration (FDA), the European Medicines Evaluation Agency (EMEA) or any other regulatory authority. Ataluren has also been known by the name of PTC124®. Ataluren is the first potential therapy designed to enable the formation of a functioning protein in a patient with a genetic disorder due to a nonsense mutation. Ataluren is taken orally and has the potential to treat the root cause of the disease by overriding the premature stop signal, so that a functional protein can be formed in a patient who has a disease due to a nonsense mutation. In other words, it seems to allow the body to overcome the genetic problem. Ataluren does not alter a patient’s genetic code or introduce genetic materials into the body. In hemophilia A and B, it may allow the body to produce increased amounts of the Factor VIII and IX proteins.

Ataluren was also generally well tolerated among the 38 patients with nmDMD and the 77 patients with nonsense mutation cystic fibrosis who participated in the Phase 2a studies. Adverse events were infrequent and usually mild to moderate in severity. A few patients with cystic fibrosis sometimes had mild burning with urination but this did not result in therapy being interrupted or discontinued. There were no safety concerns based on physical examinations, vital sign measurements, electrocardiograms, or laboratory test results.

Data from the Phase 2a studies are preliminary in nature. Studies of larger groups of patients are now being conducted over longer periods of time to more fully evaluate the safety and efficacy of ataluren. For example, 174 boys and young men with nonsense mutation Duchenne and Becker muscular dystrophy are now enrolled in a Phase 2b double blinded trial during which they are scheduled to receive ataluren or placebo for 48 weeks.

Studies in animals with a nonsense mutation in the Factor VIII or IX gene have shown that treatment with ataluren partially restores the production of Factor VIII or IX protein. It is hoped that improvements in Factor VIII or Factor IX will be seen in patients participating in the Phase 2a study. If this happens, it may be possible for ataluren to be studied further as a therapy that might prevent bleeding in patients with nmHA and nmHB and might reduce the need for episodic infusions of Factor VIII or IX.

Patients considering participating in any clinical trial should discuss this decision with their treating physician and also make sure during the informed consent process that they thoroughly understand the risks and benefits associated with the trial.

To be considered for this trial, patients must be male, at least 18 years of age, have severe hemophilia A or B (Factor VIII or Factor IX level less than 1%) due to a nonsense mutation, which can be determined through a DNA blood test called genotyping. In addition, participants in this trial must not be regularly infusing Factor VIII or Factor IX concentrates to prevent bleeding. They must have no history of inhibitor formation nor of any bleeding or coagulation abnormalities other than hemophilia. Their tests for liver and kidney function must be near normal.

Potential study participants must also have had a DNA blood test to evaluate the factor VIII or factor IX gene and know that a nonsense mutation is the cause of their hemophilia. This test is known as genotyping or full-length gene-sequencing. Patients with HA/HB who have not been genotyped should consider discussing the test with their treating physician or genetic counselor. Facilities that perform gene-sequencing can be located through the Gene Tests website (www.genetests.org); click “Laboratory Directory” to search for the locations of gene-sequencing facilities.

Additional inclusion and exclusion criteria are listed on clinicaltrials.gov at http://clinicaltrials.gov/ct2/show/NCT00947193 and will be explained in detail at the trial research centers.

The trial will continue enrolling new patients until the necessary number of participants, (approximately 24) has been reached. The sooner patients enroll in the trial, the faster the trial can be completed, and the sooner the results can be known.

During the trial, participants will visit the research center once per week. Some of these visits will be longer and some will be shorter; the longer visits may require about 2 to 3 hours. During the visits, participants will provide blood and urine samples for various laboratory tests to evaluate the effects and safety of the drug and may be asked questions about their experience in the study. An electrocardiogram will be done during the screening visit and may be repeated at other times if needed.

Participants will be required to keep a daily diary to record the number of packets of ataluren taken and any comments regarding taking the drug, and a diary to record any bleeding episodes.

Patients cannot participate in the ataluren study if they are participating in a clinical study of another investigational therapy.