H. Lundbeck A/S (DK) - Data from a post hoc analysis using desmoteplase in ischaemic stroke presented at the International Stroke Conference

H. Lundbeck A/S (Lundbeck) today announced that data presented at the International Stroke Conference (ISC) in San Antonio, Texas 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[i]<https://inpublic.huginonline.com/hugin/#_edn1>.

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.

"Stroke patients today suffer from substantial unmet medical needs and the re-analysis of the DIAS-2 study now presented at ISC suggest that patients with a detectable blood clot can benefit from desmoteplase," says Executive Vice President Anders Gersel Pedersen, Head of Drug Development at Lundbeck. "Desmoteplase has the potential to treat patients with acute ischaemic stroke up to nine hours after onset of symptoms. No treatment is available today that allows patients to reach hospital and be diagnosed within this extended time window".

DIAS-2 results and post hoc findings DIAS-2 did not confirm the positive results 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.)

Several factors may have contributed to the high response in the placebo group:

* A low baseline NIHSS (National Institute of Health Stroke Scale) score (median, 9). * A large proportion (70%) of the patients in DIAS-2 did not have a visible proximal cerebral arterial occlusion or high-grade stenosis at the time of study drug administration (i.e., they had a TIMI score of 2 or 3); in contrast, only 44% of the patients in DEDAS/DIAS had a TIMI score of 2 or 3. Post hoc analysis showed that the subgroup of patients with visible proximal cerebral arterial occlusion or high-grade stenosis on baseline angiographies had improved response for both desmoteplase doses over placebo

Percent of patients with clinical response

90 μg/kg

125 μg/kg

Placebo

DIAS (part 2)

47

60

22

DEDAS

29

60

25

Meta-analysis

38

60

23

DIAS-2

47

36

46

Visible occlusion

36

27

18

The results of the DIAS-2 post hoc analysis and a meta-analysis of results from previous DEDAS and DIAS studies strongly supported the larger trial DIAS-2. These findings provided the basis for the design of the DIAS-3 and 4 clinical trials.

About desmoteplase 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.

Patients in an earlier clinical phase III trial with desmoteplase were eligible for treatment only in case of a detectable penumbra (insufficiently perfused but still salvageable tissue area around the primary location of stroke) of at least 20% of the affected area and were not screened for presence of vessel occlusion in the larger brain arteries using angiography. The data from the re-analysis of angiographs from these patients demonstrated that, in contrast to the phase II studies, 70% of the patients in the phase III trial lacked visible vessel occlusion before treatment.

When analysing patient subgroups using presence of vessel occlusion as treatment criteria, a reduced response rate on the placebo group and a positive effect of desmoteplase versus placebo is observed, however not statistically significant due to the small sample size. Additionally, pooled results from the clinical phase II and III studies show statistically significant efficacy in favour of desmoteplase if patients without visible occlusions in the large brain arteries are excluded. These novel findings are encouraging and support continued clinical investigation in patients with acute ischaemic stroke within 3 to 9 hours after onset of stroke symptoms.

Lundbeck has obtained worldwide rights to desmoteplase from PAION AG in Germany. PAION has been supporting in the planning of the new trials.

About stroke 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. 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 66 billion in 2008.

Financial guidance The content of this release will have no influence on the Lundbeck Group's financial result for 2009 that will be announced 4 March 2010.

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About Lundbeck 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 over 5,500 people worldwide. Lundbeck is one of the world's leading pharmaceutical companies working with CNS disorders. In 2008, the company's revenue was DKK 11.3 billion (approximately EUR 1.5 billion or USD 2.2 billion). For more information, please visit www.lundbeck.com.

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[i]<https://inpublic.huginonline.com/hugin/#_ednref1> 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

Posted: February 2010

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