Summary of trial results

The pivotal Phase 2b trial of ataluren, an investigational new drug being studied in nonsense mutation Duchenne/Becker muscular dystrophy (DBMD), was completed in late 2009. It had enrolled 174 patients at 37 trial sites in 11 countries on four continents. As PTC and statistics experts have analyzed the complex data from this trial using various statistical methods, the company has come to understand that the results are very promising.

Efficacy

• The trial had low-dose ataluren and high-dose ataluren arms as well as a placebo arm. The main criterion, or endpoint, used to determine differences in performance among the three arms was the Six Minute Walk Test, which measured, every six weeks, the distance that participants could walk in 6 minutes (6MWD).

• Participants receiving low-dose ataluren (10, 10, 20 mg/kg) showed a clinically meaningful difference (approximately 30 meters) in the change in their 6MWD results when compared to the placebo arm.

• The FDA requires that trial sponsors specify in advance which statistical models will be used to analyze data at the end of a study. The data was first analyzed using the pre-specified statistical method. The unexpected complexity of the ataluren data could not be fully addressed using this method, so it was necessary to use a different (ie, post hoc) statistical model to fully understand the results.

o A post hoc statistical analysis, using a model suggested by independent statistics experts, showed an average difference between low-dose ataluren and placebo of 31.3 meters (103 feet) in the 6MWD. The p-value for this result is 0.0561. A p-value is a test of statistical significance that measures how likely it is that a result is due to an actual effect rather than to chance. In this case, the post hoc corrected p value of 0.0561 indicates that there is only about a 5% possibility that the results could have been obtained if ataluren was no different than placebo.

o A second measure used to compare the effects of ataluren at the two different doses and against placebo was the time it took for the 6MWD to worsen by 10% and remain so. This was defined as “time to persistent 10% worsening.” This analysis indicated that patients receiving low-dose ataluren experienced slower disease progression than patients receiving placebo. By the end of the trial, 26% of the low-dose patients were persistently 10% worse in 6MWD than when they started, compared to 48% in the high-dose arm and 44% in the placebo arm (post hoc p=0.0652 for low-dose ataluren vs placebo).

• The 6MWD results from the high-dose (20, 20, 40 mg/kg) arm were similar to the placebo arm. At the completion of the preliminary data analysis, all patients in three ongoing DBMD clinical trials (Phase 2a and 2b extension studies and a non-ambulatory study) were receiving the high dose. Although an independent data monitoring committee agreed that ataluren was well tolerated by patients, the committee recommended that the trials be suspended because all patients in ongoing trials were on the high dose.

Safety

• Safety results showed that ataluren was generally well tolerated:
o Adverse events were similar across all three arms of the study: high-dose, low-dose and

placebo.
o No patients discontinued treatment due to an adverse event.
o Serious adverse events were infrequent and none was considered to be related to ataluren.