Zicronapine

Zicronapine shows significant positive data in clinical phase II in the treatment of patients with schizophrenia - planning for continued clinical work


Corporate Release No 392

18 December 2009

H. Lundbeck A/S (Lundbeck) today announced strongly positive headline results
from the clinical trials in the phase II development programme with zicronapine
in schizophrenia. The programme consisted of two studies which in total involved
approximately 375 patients.

In the two recently completed randomised clinical phase II trials, zicronapine
was tested in several dosages between 3-10 mg/day. The two studies were
exploratory and therefore not powered to show clear statistical differences.
However, in the studies zicronapine did show clear statistical significant
separation from placebo at 7 and 10 mg and very convincing efficacy and safety
data when compared to olanzapine justifying further development.

In the placebo-controlled trial, zicronapine showed clear dose-response and a
statistically significant improvement in PANSS score on both 7 and 10 mg. In the
olanzapine-referenced study, zicronapine showed comparable reduction in PANSS
score.

From both trials it can be concluded that zicronapine was safe and
well-tolerated. In the olanzapine-referenced study the number of withdrawals was
similar to the level of withdrawals in the olanzapine-group.

"We are pleased to see the efficacy and supportive data enabling us to continue
the development program," says Executive Vice President Anders Gersel Pedersen,
Head of Drug Development at Lundbeck. "We are also pleased that the good safety
profile seen in earlier studies now is confirmed in a much larger patient
population.?

In the coming months, Lundbeck will finalise the planning for additional
clinical work including plans for the pivotal programme.

About the study
In the placebo-controlled clinical phase II study approximately 280 patients
from 11 countries suffering from schizophrenia were enrolled. Eligible patients
have been randomised in a 2:1 ratio to blinded treatment with either zicronapine
(3, 5, 7 and 10 mg/day) or placebo for 8 weeks. The primary focus of this trial
was safety and tolerability measured by adverse events, clinical safety
laboratory tests and metabolic parameters. Secondary outcome measures included
Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression ?
Severity/Improvement (CGI-S/I) scores.

In the second clinical phase II study approximately 93 patients were enrolled
from nine countries. Eligible patients were randomised to treatment with either
flexible doses (5-7 mg/day) of zicronapine or flexible doses of olanzapine
(10-15 mg/day) for 12 weeks. The efficacy and the safety of zicronapine were
explored in comparison to olanzapine. The primary outcome measures included the
PANSS score. Secondary outcome measures included CGI-S/I and Calgary Depression
Scale for Schizophrenia (CDSS) scores.

About zicronapine (previously known as Lu 31-130)
Zicronapine has a multi-receptorial profile. In vitro and in vivo, zicronapine
has shown potent antagonistic effects at dopamine D(1), D(2) and 5-HT(2a)
receptors. Based on the profile from antipsychotic animal models, zicronapine
was expected to show clear and convincing effects in patients with schizophrenia
and likely associated with low potential for neurological side effects and a
benign safety/tolerability profile.

schizophrenia.com