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.
Lundbeck contacts
Investors: Media:
Jacob Tolstrup Mads Kronborg
Vice President, IR & Communication Media Relations Manager
+45 36 43 30 79 +45 36 43 28 51
Palle Holm Olesen
Chief Specialist; Investor Relations
+45 36 43 24 26
Magnus Thorstholm Jensen
Investor Relations Officer
+45 36 43 38 16
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 <li> February
23-26, 2010 <li> San Antonio, TX, USA
[HUG#1388501]
