Pipeline
In December 2006, we initiated two clinical trials, FREEDOM-C and FREEDOM-M, to evaluate the safety and efficacy of oral treprostinil in patients with PAH.
The FREEDOM-C clinical trial was a study of patients currently on approved background therapy using a PDE-5 inhibitor, such as Revatio , or an ERA, such as Tracleer , or a combination of both. We completed enrollment for FREEDOM-C in May 2008 and in November 2008, we announced that FREEDOM-C failed to achieve statistical significance. Preliminary analysis of the data revealed that the initial tablet strength was too high, which contributed to an inability to dose titrate (increase the dose to tolerability) and prevented the attainment of optimal dosing levels. Consequently, the overall treatment effect of the therapy was muted. However, we believe that the results of the FREEDOM-C clinical trial, particularly as they relate to treatment effect and dosing, support our continued development of oral treprostinil. Accordingly, we commenced a second clinical trial, FREEDOM-C, to continue studying dosage and efficacy of oral treprostinil in PAH patients on approved background therapy. Enrollment in FREEDOM- Cbegan in
June 2009.
The FREEDOM-M clinical trial is a 12-week study of newly-diagnosed PAH patients not currently on any background therapy. Based on our observations from the FREEDOM-C clinical trial relating to patient tolerability and tablet strength, we submitted a protocol amendment to the FDA in February 2009 seeking to add patients to the ongoing FREEDOM-M trial. These additional patients will be provided a lower-strength tablet (0.25 mg) when they begin the trial and their doses will be titrated in 0.25 mg increments, which we believe will improve tolerability. In addition, our amendment to the FREEDOM-M protocol seeks to limit the primary statistical analysis of the trial to only those patients who started the trial using the 0.25 mg tablet. In amending FREEDOM-M we hope to achieve the following objectives: (i) to assess more accurately the effectiveness of oral treprostinil; (ii) to improve patient tolerability of oral treprostinil so that an effective maintenance dose can be attained; and (iii) to reduce the rate of premature discontinuation due to adverse events. The statistical assumptions of the amended protocol provide for 90% power to observe a 45 meter treatment benefit in six-minute walk distance at the significance level of 0.01. If we are able to successfully implement these protocol amendments, we believe that the results will reflect the expected dosing regimen for oral treprostinil. In April 2009, we began enrolling patients in FREEDOM-M under the amended protocol.