Lundbeck’s schizophrenia drug Serdolect could lead to sudden cardiac death, fears USFDA

Sold under the brand name Serlect in Mexico. Sertindole was recalled from the market in late 1998

U.S. FDA has raised concerns about the Danish pharmaceutical firm Lundbeck’s Serdolect , a drug seeks to treat schizophrenia pending approval.

Though Serdolect appeared to be effective in treating symptoms associated with schizophrenia, it does possess a possible of sudden cardiac death, said reviewers of the US FDA.

Besides treating schizophrenia, H Lundbeck is seeking approval to claim Serdolect reduces suicidal behavior in schizophrenics, according to a memo prepared by the reviewing committee to be submitted for the advisory panel.

The committee will discuss safety and efficacy issues with new drug application (NDA) 20-644, Serdolect (sertindole) tablets, Lundbeck USA, proposed for the treatment of schizophreniad, on April 7, 2009, documents released on Friday said.

The committee will ask an advisory panel whether there is enough evidence to back the suicidal behavior claim, and whether the drug is safe and effective for schizophrenia.

Serdolect contains sertindole, one of the newer antipsychotic medications available.

Like the other atypical antipsychotics, it has activity at dopamine and serotonin receptors in the brain. It is classified chemically as a phenylindole derivative.

Sertindole is sold under the brand name Serlect in Mexico.

H. Lundbeck had announced in September last year that the U.S. Food and Drug Administration (FDA) has completed the initial check for completeness and accepted the New Drug Application on Serdolect for the treatment of schizophrenia for review.

This is the first new drug application (NDA) submitted in the US by Lundbeck. Before that Lundbeck launched Serdolect in Europe, South and Central America, Asia, and the Middle East.

“We are very pleased that we have submitted an NDA for Serdolect as this will potentially provide patients suffering from schizophrenia in the US with a new treatment option,” said Anders Gersel Pedersen, head of Lundbeck’s drug development, while making the announcement.

Lundbeck said Serdolect is an effective antipsychotic drug for the treatment of schizophrenia without sedative effect. Sedation may add to the cognitive problems inherent in schizophrenia. The lack of sedative and anticholinergic effects is believed to benefit cognition, which often is impaired in patients suffering from schizophrenia.

Further to that, studies show that sertindole effectively normalizes laboratory induced cognitive impairment in animals, and that sertindole treatment has shown long lasting improvements in elementary cognitive processes in humans. This advantage may be linked to the high 5HT6a receptor affinity.

The efficacy, tolerability and safety of Serdolect has already been confirmed in more than 70,000 patients. Serdolect’s clinical and pharmacological profile indicates that the drug may improve their daily functioning and their quality of life and reduce the risk of relapse, according to the company.

Sertindole was voluntarily withdrawn from the market late 1998 due to concerns over the risk of cardiac death. Arrhythmia and sudden death may be caused by a QTc (QTc interval is a heart rate-corrected value that represents the time between the onset of electrical depolarisation of the ventricles and the end of repolarisation.) prolongation reported in some individuals.

However, large cohort analyses, as well as non-clinical evidence, has proven that all-cause mortality with sertindole is comparable with risperidone or olanzapine. The risk/benefit profile of sertindole did not motivate a permanent withdrawal from the market.

The suspension was lifted in 2002 for the Sertindole Cohort Prospective (SCoP) study. This large post-marketing obeservational study revealed no increase in overall or cardiac mortality. Based on an evaluation by the Committee for Human Medicinal Products (CHMP), the European Commission recommended lifting the marketing restrictions on sertindole in 2005 with a regulatory requirement of ECG monitoring.

The regulatory agencies in many countries have now implemented the approval of sertindole on a national level, and sertindole is available in more than 20 countries across the world.

Schizophrenia is a serious mental disorder affecting up to 1% of the world’s population. In many patients this chronic disorder start during late adolescence or early adulthood leading to severe changes in the patient’s way of thinking and perceiving the outside world.

During the course of the illness, periods during which the patient is in an acute psychotic condition and suffering from definite hallucinations and delusions. Schizophrenia is  alternate with more stable periods during which the patient experiences a significant reduction in symptoms.

Many schizophrenics have difficulty in establishing social contact, completing an education programme or holding a normal job, even in stable periods. Schizophrenia patients may have significant difficulties in performing daily activities necessary for independent living.

Schizophrenics also express suicidal behaviour. Suicide is a leading cause of premature deaths among patients with schizophrenia. Schizophrenia is also associated with increased medical morbidity like respiratory or cardiovascular diseases which all contribute to a significantly lower life expectancy.

Schizophrenia is often disabling and produces important emotional and financial hardship for the patient. Schizophrenia also causes a major economic burden to the patient’s family, society, not only due to the direct treatment costs but also because of a reduced ability to work.

Lundbeck is a research-based company, engaging in research to find new drugs for treatment of CNS disorders, including depression, schizophrenia, Alzheimer’s disease, Parkinson’s disease and insomnia.