Date: 2014-12-17
Type of
information: discontinuation of development
phase: 3
Announcement: discontinuation of development
Company: Lundbeck (Denmark)
Product: desmoteplase
Action
mechanism:
- protein. Desmoteplase, a fibrin-dependent plasminogen activator, is a genetically engineered version of a clot-dissolving protein found in the saliva of the vampire bat Desmodus rotundus. It has received fast-track designation from the FDA for the treatment of acute ischaemic stroke.
Disease: acute ischaemic stroke
Therapeutic
area: Cerebrovascular diseases
Country:
Trial
details:
- DIAS-3 was a multi-centre, randomised, double-blind, placebo-controlled study in 479 patients from 18 countries in Europe and Asia. Patients with symptoms of stroke and a treatable ischaemic stroke pathology (proximal cerebral vessel occlusion/high-grade stenosis without signs of extensive infarction, intracranial haemorrhage or sub-acute infarction), as assessed by magnetic resonance imaging (MRI) or computerised tomography (CT) scanning were randomised to receive either desmoteplase (90 µg/kg) or placebo within three to nine hours of symptom onset.
Latest
news:
- • On December 17, 2014, Lundbeck announced that following the evaluation of the entire available data package including results from DIAS-4 on the investigational compound desmoteplase, Lundbeck has decided to cease further development in ischaemic stroke. Alternatives including divestiture are now being evaluated. In both the DIAS-3 and DIAS-4 study patient sub-groups experienced positive effects and the studies confirmed the favourable safety profile of desmoteplase by indicating good safety and tolerability data. It was, however, insufficiently clear how to select patients in future prospective studies. It has therefore been decided to discontinue the development project in Lundbeck. Following this decision a write-down of DKK 309 million will be taken in the fourth quarter of 2014 and recognized in the R&D costs as communicated earlier this year.
• On June 27, 2014, Lundbeck announced the initial headline conclusions from DIAS-3, the first of two phase III clinical trials of desmoteplase for the treatment of adult patients with acute ischaemic stroke. The study did not meet the primary endpoint, i.e. the proportion of patients with a favourable outcome of modified Rankin Scale (mRS) score 0-2 at Day 90 was not statistically different between patients treated with desmoteplase (51.3%) and patients in the placebo control group (49.8%). The DIAS-3 study confirmed the favourable safety profile of desmoteplase by providing excellent safety and tolerability data. Desmoteplase was well tolerated with adverse events at placebo level. In particular, the mortality was equal between treatment groups and the rate of symptomatic intracranial haemorrhage (the most serious adverse event associated with the current available thrombolytic treatment) after desmoteplase treatment was also comparable to placebo. The DIAS-3 study protocol defined the target population as patients with symptoms of stroke and treatable ischaemic stroke pathology (proximal cerebral vessel occlusion/high-grade stenosis without signs of extensive infarction, intracranial haemorrhage or sub-acute infarction). Analysing only the patients fulfilling the protocol requirements (per protocol population) a favourable effect of desmoteplase was observed relative to placebo measured by mRS. This result is in line with the hypothesis based on the earlier post-hoc analysis of DIAS-2 on the target patient population. As a consequence of the failure to meet the primary outcome, but considering the efficacy signal in the per protocol population and the excellent safety and tolerability, further development will be evaluated with advice from key clinical and regulatory experts during the next few months in order to evaluate if a path forward is feasible.Further results of the study will be presented at a scientific congress and published in a scientific journal.
Is
general: Yes
