PAION sees continued development rationale for Desmoteplase based on findings from Phase III analysis
Reasons identified for high placebo response rate in Phase III stroke study DIAS-2
PAION AG reported that it has reviewed findings from the analysis of the DIAS-2 (Desmoteplase in Acute ischemic Stroke) study results. In contrast to previous phase II studies, the DIAS-2 study did not meet its primary efficacy endpoint due to a lack of improvement in the Desmoteplase groups over placebo. Therefore, the clinical efficacy of Desmoteplase as demonstrated in two smaller Phase II studies (DIAS and DEDAS) could not be confirmed. However, the analysis of the patient subgroups has generated new findings regarding the unexpectedly high placebo rate observed in the DIAS-2 study and provides indications for the efficacy of Desmoteplase, although short of any statistical significance due to the small patient numbers of the subgroups.
From the study's top-line results, it was already known that patients in the DIAS-2 study showed on average relatively mild symptoms of stroke. Now angiographs have been evaluated as part of the analysis. The data reveal that in contrast to DIAS and DEDAS, a high percentage of DIAS-2 patients did not have a blood clot in the main brain arteries at the start of treatment, despite the detection of salvageable brain tissue (penumbra) surrounding the infarct core according to the DIAS-2 study protocol. So far, stroke experts have assumed the presence of a penumbra to be a key indication of both visible (in the larger brain arteries) and non-visible blood clots (in smaller arteries). The new findings are crucial since Desmoteplase's main mechanism of action is to dissolve blood clots in occluded arteries.
Consequently, the high percentage of DIAS-2 patients lacking a blood clot in their main brain arteries seems to be a major reason for the similar clinical outcome across the different dose groups including placebo.
In addition, findings from patient subgroups with a detectable blood clot in their main brain arteries indicate that Desmoteplase could potentially show efficacy compared to placebo. In particular, the efficacy of the drug seemed to increase with the severity of the vessel occlusion. However, these findings have to be confirmed in a larger patient group in order to achieve statistical significance.
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