FDA advisory committee recommends approval of Abbott's Serlect for treatment of schizophrenia.

WASHINGTON--(BUSINESS WIRE)--July 16, 1996--The Psychopharmacologic Drugs Advisory Committee to the U.S. Food and Drug Administration (FDA) Monday, July 15, 1996, voted to recommend that Serlect(TM) (sertindole) be approved for the treatment of psychotic disorders.

"This is a major step toward providing a significant improvement in the treatment of schizophrenia," says Andre Pernet, Ph.D., vice president of pharmaceutical products research and development at Abbott. "Serlect was designed using the rational approach to drug development. Unlike most antipsychotics, which commonly cause debilitating motor side effects, Serlect was developed to be more selective and target those receptors in areas of the brain thought to be involved with symptoms of psychosis."

Among the data reviewed by the committee were the results of a seven-arm, multi-center, double-blind, eight-week clinical trial comparing three doses of Serlect (12, 20, and 24 mg/day) to three doses of haloperidol (4, 8, and 16 mg/day) and placebo. In the study, all Serlect doses and haloperidol doses showed significant improvement in the positive symptoms of schizophrenia compared with placebo and in reducing the total scores on the Positive and Negative Symptoms Scale (PANSS). Only Serlect at a dose of 20 mg/day improved negative symptoms, as measured by PANSS Negative Symptom Subscale. On a comprehensive, global scale of improvement, (the Clinical Global Impression scale or CGI), all doses of Serlect and haloperidol were associated with significant improvement compared to placebo.

The positive symptoms of schizophrenia include delusions, hallucinations, and disorganized speech and behavior. Negative symptoms include apathy, social withdrawal, and decrease in productivity of thought and speech.

Patients using haloperidol experienced motor side effects called extrapyramidal symptoms, or EPS, at rates significantly higher than those given placebo. EPS profiles for Serlect at all doses were clinically and statistically indistinguishable from placebo. In addition, patients treated with any of the three doses of Serlect exhibited less EPS than patients using any of the three doses of haloperidol. Researchers measured EPS rates by the number of EPS related adverse events, use of anti-EPS medication, and three standard movement rating scales. This EPS-profile is important because EPS can be extremely disabling, can cause severe discomfort, and may reduce treatment compliance.

"Serlect represents a new generation of medicines for psychosis that could dramatically improve the treatment of this devastating illness," says John M. Kane, M.D., professor of psychiatry at Albert Einstein College of Medicine in New York. "The need is great for antipsychotic agents that do not produce EPS." Studies show that, among patients receiving currently available short-term treatment, as many as 70 percent may have some clinically important EPS side effects.

While recommending approval, the committee discussed the need to make patients aware of a condition that potentially increases the risk of abnormal heart rhythms. In clinical studies, approximately 4 percent of patients showed an increase in QT intervals -- alterations in the heart's usual rhythm. QT interval prolongation is sometimes a precursor for serious alterations of heart rhythm.

According to Edward Pritchett, M.D., chief of cardiology and clinical pharmacology at Duke University Medical Center, and an independent cardiac specialist who presented data at the meeting, "Intermittent QT interval prolongations have occurred in rare cases of sudden death in patients taking Serlect. However, sudden death has historically been associated with schizophrenia, while QT interval prolongation has also been associated with other antipsychotics currently used by schizophrenia patients."

In clinical trials, adverse events with an incidence of 5 percent or more in patients treated with sertindole and at least twice that of placebo were: nasal congestion, dry mouth, abnormal ejaculation, characterized as decreased ejaculatory volume, and vaginitis.

In clinical trials, Serlect was administered once daily in a capsule formulation. It is a novel, limbic-selective antipsychotic drug. As with other antipsychotics, the exact mechanism of action of Serlect is not known. However, in pre-clinical studies, Serlect was demonstrated to be a potent antagonist at dopamine D2-, serotonin 5HT2-, and alpha1-receptors without activity at histaminic H1 or muscarinic receptors. This selectivity suggests that Serlect mitigates both the positive and negative symptoms of schizophrenia, but should not produce sedative effects or anticholinergic effects related to these other receptors.

Schizophrenia is a devastating, chronic mental disorder that affects an estimated one out of every 100 people. It is characterized by hallucinations, a disintegration in the process of thinking, loss of contact with reality, and emotional unresponsiveness. The condition, which generally manifests in early adulthood, costs the United States approximately $16 billion to $33 billion annually.

Serlect is licensed for marketing in the United States by Abbott Laboratories from H. Lundbeck A/S of Denmark. Abbott Laboratories filed a New Drug Application with the U.S. Food and Drug Administration in September 1995 seeking clearance for the use of Serlect in the treatment of psychosis. Sertindole is approved for marketing in the United Kingdom under the trade name Serdolect.

Abbott Laboratories is a worldwide manufacturer of health care products, employing 50,000 people. In 1995, the company's sales and net earnings were $10.0 billion and $1.7 billion, respectively, with earnings per share of $2.12.

CONTACT: Abbott Laboratories, Abbott Park, Ill.

Douglas Petkus, 847/938-3531

Kimberly Modory, 847/938-8439