Desmoteplase enters clinical phase II in Japan in ischaemic stroke representing Lundbeck’s first clinical programme in Japan
H. Lundbeck A/S (Lundbeck) today announced the initiation of the first Japanese clinical phase II trial with desmoteplase (DIAS-J) in the treatment of acute ischaemic stroke. This study is required for the approval of the substance for the Japanese market. In 2009 Lundbeck successfully performed a phase I study in around 30 healthy Japanese volunteers with no safety concern observed.
The primary objective of this randomised, double-blind, placebo-controlled, dose-escalation study is to evaluate the safety and tolerability of desmoteplase in 48 Japanese patients with acute ischaemic stroke. Two doses of desmoteplase (70 and 90 µg/kg) will be tested versus placebo. The efficacy of desmoteplase will be assessed after 90 days. The DIAS-J study is expected to take around 1½ years to conduct and once DIAS-J is completed the subsequent development strategy and the clinical data package necessary for a Japanese NDA will be determined.
“We are very pleased with the progress of this project in order to ensure that also the Japanese stroke patients get access to this innovative medicine and thereby potentially preventing significant disabilities,” says Executive Vice President Anders Gersel Pedersen, Head of Drug Development at Lundbeck. “This clinical phase II programme also represents the first Lundbeck-run clinical programme in Japan which represents a major step for Lundbeck”.
It is estimated that there are approximately 250,000 cases of acute ischaemic stroke in Japan[i]. In Japan, stroke is the third-leading cause of death with mortality rate of 105 per 100,000 populations, and it remains the most common cause of permanent disability in adults[ii].
Desmoteplase, the most fibrin-specific plasminogen activator known today, 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 U.S. Food and Drug Administration for the indication of acute ischaemic stroke.
Lundbeck presented data at the International Stroke Conference (ISC) in San Antonio, Texas in February 2010 which showed very supportive data for desmoteplase. Post hoc analysis of data from the clinical phase III study, DIAS 2, showed that the subgroup of patients with visible arterial occlusion or high-grade stenosis on baseline angiographies had improved response for desmoteplase over placebo[iii].
Furthermore, it can be concluded that compared to previous trials (DIAS and DEDAS), patients in DIAS-2 had less severe strokes and smaller mismatch volumes. A large proportion (70.4%) of the patients in DIAS-2 did not have a visible arterial occlusion or high-grade stenosis at the time of study drug administration. These differences in baseline characteristics can explain findings such as the unexpectedly high response in the placebo group.
The data suggest that patients with a so-called Thrombolysis in Myocardial Infarction (TIMI) score of 0 or 1 revealed lower response rates in the placebo group (18%) and higher response rates in the desmoteplase groups (36% and 27% for desmoteplase 90 μg/kg and 125 μg/kg, respectively).
Evidence of safety and efficacy was obtained in the Dose Escalation of Desmoteplase in Acute ischaemic Stroke (DEDAS, n=37) and Desmoteplase in Acute Ischaemic Stroke (DIAS, n=102) phase II trials. The DIAS-2 phase III trial (n=186) supported the safety profile of desmoteplase but did not replicate the positive efficacy findings of DEDAS and DIAS, possibly because of the high placebo response rate (46% placebo vs. 47% and 36% for desmoteplase 90 and 125 μg/kg, respectively).
The findings from the post hoc analysis provided the basis for the design of the currently ongoing clinical phase III programme (DIAS-3 and 4). DIAS-3 and DIAS-4 are randomized, double-blind, placebo-controlled, multinational phase III twin trials, aiming to enrol 800 patients with acute ischaemic stroke.
Lundbeck has obtained worldwide rights to desmoteplase from PAION AG in Germany. PAION has been supporting in the planning of the new trials.
Stroke is the third leading cause of death in the industrialised world and a leading cause of serious, long-term disability. In the US alone, approximately 700,000 people suffer an ischaemic stroke each year, and around 8-12% of them die within 30 days. On average, every 40 seconds someone in the US has a stroke. Strokes can - and do - occur at any age. Nearly one quarter of strokes occur in people under the age of 65[iv]. For the US, the American Heart Association estimates the financial burden of stroke due to in-hospital costs, long-term care programmes and productivity losses to approximately USD 69 billion in 2009.
The content of this release will have no influence on the Lundbeck Group’s financial result for 2010.
H. Lundbeck A/S (LUN.CO, LUN DC, HLUKY) is an international pharmaceutical company highly committed to improve the quality of life for people suffering from central nervous system (CNS) disorders. For this purpose Lundbeck is engaged in the research and development, production, marketing and sale of pharmaceuticals across the world, targeted at disorders like depression and anxiety, schizophrenia, insomnia, Huntington’s, Alzheimer’s and Parkinson’s diseases.
Lundbeck was founded in 1915 by Hans Lundbeck in Copenhagen, Denmark, and employs today approximately 5,900 people worldwide. Lundbeck is one of the world’s leading pharmaceutical companies working with CNS disorders. In 2009, the company’s revenue was DKK 13.7 billion (approximately EUR 1.8 billion or USD 2.6 billion). For more information, please visit www.lundbeck.com.
[i] Decision Resources: “Acute Ischaemic Stroke”, December 2009
[ii] Y. Yoneda et al.: Hospital cost of ischaemic stroke and intracerebral hemorrhage in Japanese stroke centers / Health Policy 73 (2005) 202-211
[iii] Gregory W. Albers, Rüdiger von Kummer, on behalf of the DIAS-3 and DIAS-4 Study Group: “Desmoteplase 3-9 Hours After Acute Ischaemic Stroke: An Update on the DIAS Clinical Trial Program”. International Stroke Conference 2010 February 23-26, 2010 San Antonio, TX, USA
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