Schizophrenia drug zicronapine shows better safety profile in human studies: Lundbeck

Zicronapine, a schizophrenia drug candidate currently being investigated by H Lundbeck, has shown positive data in phase 2 clinical studies.

Zicronapine (previously known as Lu 31-130) 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 safety profile, Lundbeck said in a press release.

H. Lundbeck A/S’ zicronapine clinical development programme consisted of two studies which in total involved approximately 375 patients.

In the randomised clinical phase II trials, zicronapine was tested in several dosages between 3-10 mg/day.

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, though the two studies were exploratory in nature.

Zicronapine showed clear dose-response and a statistically significant improvement in PANSS score on both 7 and 10 mg, in the placebo-controlled trial.

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.

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.

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

Schizophrenia is a serious and disabling mental disorder that affects approximately 1% of the world’s population. Antipsychotic drugs remain the cornerstone in the pharmacotherapy of schizophrenia.

However, none of the available drugs is ideal, in particular because of their complex safety profile and the limited effectiveness against certain symptoms of the disease. Only one dimension of the morbidity, that is, the positive symptoms, can be expected to respond to treatment whereas negative symptoms and cognitive deficits are, at best, only marginally targeted.

Therefore, the current antipsychotic drugs leave much room for improvement and call for new, more effective pharmacotherapies in the treatment of schizophrenia, according to Lundbeck.

Headquartered in Copenhagen, Denmark, L. Lundbeck A/S is engaged in the research and development, production, marketing of pharmaceuticals targeted at disorders like depression and anxiety, schizophrenia, insomnia, Huntington?s, Alzheimer?s and Parkinson?s
diseases.

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).