Health Boards
Tue-18-12-2012, 13:56 PM
Actelion announced today that its selective S1P1 modulator, ponesimod, successfully met the primary endpoint - the proportion of patients with at least 75% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI75) at week 16 - in a double blind, placebo-controlled study conducted in 326 patients with moderate to severe chronic plaque psoriasis.
Results of the primary endpoint were highly statistically significant with both tested doses. With Ponesimod 20 mg, 46 % of patients improved by at least 75 % at week 16 (p<0.0001 versus placebo). With Ponesimod 40 mg, 48.1% of patients improved by at least 75 % at week 16 (p<0.0001 versus placebo). An improvement by at least 75 % was observed at week 16 in 13.4% of the placebo treated patients. Both doses were administered once daily.
At the end of induction, ponesimod patients improving at least 50% or more in their PASI score at week 16 were re-randomized to either continuation of the same dose of ponesimod, or to placebo.
After the initial 16 week induction phase of the study, further improvement was seen with ponesimod during the 12-week double-blind, placebo-controlled maintenance period. Among patients continuing on ponesimod 20 and 40mg, 71 % and 77 % achieved PASI75 at the end of the study, respectively.
Efficacy was also demonstrated across other endpoints of the study, including Physician Global Assessment (PGA) at week 16.
Guy Braunstein, M.D. and Head of Clinical Development at Actelion commented: "This is the first time that this mechanism has demonstrated efficacy with psoriasis patients. Analysis during the maintenance period of the study showed patients continued to improve beyond the initial 16 week induction phase. Having conducted such a large Phase II study we have the information we need for the design of the pivotal Phase III program."
Safety and tolerability data from the study are consistent with the safety profile of ponesimod observed in previous studies conducted including the Phase II study with multiple sclerosis patients. At initiation of ponesimod treatment, transient reductions in heart rate and less frequently, a transient effect on atrioventricular conduction were observed in the study as expected. The most frequent adverse events (AEs) reported for ponesimod was dose-dependent dyspnea and asymptomatic liver enzyme elevations. Overall, there were no indications of an increased infection rate with ponesimod in the study with the exposure to ponesimod up to 28 weeks. The safety data-base from all studies with ponesimod, now comprises more than 1,100 patients and healthy volunteers with some patients treated for up to 3.3 years.
Jean-Paul Clozel, M.D. and Chief Executive Officer commented: "We are excited to now know that ponesimod, originating from Actelion's discovery effort, has the potential to become an important treatment option in immune-mediated disorders in addition to multiple sclerosis. Actelion will rapidly move forward with the preparation of the pivotal program and discussions with health authorities for the psoriasis indication."
Once full data analysis has been concluded, Actelion will discuss the details of the upcoming Phase III program with health authorities. Actelion will present the results of this dose-finding study through scientific presentations and publications.
Source: NO LINKS ALLOWED
Results of the primary endpoint were highly statistically significant with both tested doses. With Ponesimod 20 mg, 46 % of patients improved by at least 75 % at week 16 (p<0.0001 versus placebo). With Ponesimod 40 mg, 48.1% of patients improved by at least 75 % at week 16 (p<0.0001 versus placebo). An improvement by at least 75 % was observed at week 16 in 13.4% of the placebo treated patients. Both doses were administered once daily.
At the end of induction, ponesimod patients improving at least 50% or more in their PASI score at week 16 were re-randomized to either continuation of the same dose of ponesimod, or to placebo.
After the initial 16 week induction phase of the study, further improvement was seen with ponesimod during the 12-week double-blind, placebo-controlled maintenance period. Among patients continuing on ponesimod 20 and 40mg, 71 % and 77 % achieved PASI75 at the end of the study, respectively.
Efficacy was also demonstrated across other endpoints of the study, including Physician Global Assessment (PGA) at week 16.
Guy Braunstein, M.D. and Head of Clinical Development at Actelion commented: "This is the first time that this mechanism has demonstrated efficacy with psoriasis patients. Analysis during the maintenance period of the study showed patients continued to improve beyond the initial 16 week induction phase. Having conducted such a large Phase II study we have the information we need for the design of the pivotal Phase III program."
Safety and tolerability data from the study are consistent with the safety profile of ponesimod observed in previous studies conducted including the Phase II study with multiple sclerosis patients. At initiation of ponesimod treatment, transient reductions in heart rate and less frequently, a transient effect on atrioventricular conduction were observed in the study as expected. The most frequent adverse events (AEs) reported for ponesimod was dose-dependent dyspnea and asymptomatic liver enzyme elevations. Overall, there were no indications of an increased infection rate with ponesimod in the study with the exposure to ponesimod up to 28 weeks. The safety data-base from all studies with ponesimod, now comprises more than 1,100 patients and healthy volunteers with some patients treated for up to 3.3 years.
Jean-Paul Clozel, M.D. and Chief Executive Officer commented: "We are excited to now know that ponesimod, originating from Actelion's discovery effort, has the potential to become an important treatment option in immune-mediated disorders in addition to multiple sclerosis. Actelion will rapidly move forward with the preparation of the pivotal program and discussions with health authorities for the psoriasis indication."
Once full data analysis has been concluded, Actelion will discuss the details of the upcoming Phase III program with health authorities. Actelion will present the results of this dose-finding study through scientific presentations and publications.
Source: NO LINKS ALLOWED