MSD (MSD is a tradename of Merck & Co., Inc., with headquarters in Whitehouse Station, N.J., U.S.A). announced today that the European Commission has approved the Marketing Authorization Application (MAA) for SYCREST® (asenapine) sublingual tablets for the treatment of moderate to severe manic episodes associated with bipolar I disorder in adults. Today's decision was based on recommendations from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP). The Commission Decision applies to all 27 European Member States.
"Bipolar I disorder is difficult to manage, and patients frequently discontinue therapy for a variety of reasons," said Eduard Vieta, M.D., Ph.D., professor of psychiatry at the University of Barcelona, and director of the Bipolar Disorders Program of the Hospital Clinic, Barcelona, Spain. "Having multiple treatment options is vital for patients, and asenapine represents a new option for this serious disease."
The European Commission approval of SYCREST, an atypical antipsychotic, for the treatment of manic episodes in bipolar I disorder, was based on a review of efficacy data from a clinical trial program, which included nearly 1,300 patients with bipolar mania. SYCREST is marketed as SAPHRIS® (asenapine) sublingual tablets in the United States.
Clinical Trial Overview
Efficacy of SYCREST was demonstrated in two similarly-designed, three-week, randomized, double-blind, placebo- and active-controlled (olanzapine) monotherapy trials of adult patients who had bipolar I disorder with an acute manic or mixed episode with or without psychotic features. Asenapine demonstrated superior efficacy to placebo in the reduction of manic symptoms over three weeks. A statistically significant difference between asenapine and placebo was seen as early as day two.
These pivotal short-term studies were extended via a nine-week, double-blind, non-inferiority study to assess maintenance of efficacy and safety for up to 12 weeks. Maintenance of effect during the episode after 12 weeks of randomized treatment was observed. These studies were further extended for 40 weeks to assess safety for up to a total 52 weeks.
Additionally, efficacy of SYCREST as adjunctive therapy to the mood stabilizers lithium or valproate was demonstrated in a 12-week, placebo-controlled trial involving 326 patients with a manic or mixed episode of bipolar I disorder, with or without psychotic features. The addition of asenapine as adjunctive therapy in patients who were partially non-responsive to lithium or valproate monotherapy for two weeks at therapeutic serum levels resulted in superior reduction of manic symptoms versus lithium or valproate alone at weeks three and 12.
"SYCREST reflects MSD's ongoing commitment to innovative therapies in the area of neuroscience," said Armin Szegedi, M.D., head of Psychiatry, Neuroscience Clinical Research, Merck. "Today's approval provides a new treatment for patients in Europe that is intended to help address the needs of one of the most serious mental illnesses."
Approximately 4,500 subjects, including more than 3,150 patients in phase II/III studies, have contributed to asenapine's safety and tolerability data. In clinical studies, asenapine was generally well tolerated. The most common side effects seen in more than 10% of patients included somnolence and anxiety. Other common side effects seen in between one and 10 patients per 100 included weight gain, increased appetite, dystonia (slow or sustained muscle contractions), akathisia (restlessness), dyskinesia (involuntary muscle contractions), parkinsonism (slow movements, tremor), sedation, dizziness, dysgeusia (change in taste), oral hypoaesthesia (numb feeling of the tongue or in the mouth), increase in alanine aminotransferase (liver protein levels), muscle rigidity, and fatigue. SYCREST is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.
In the combined short-term and long-term SYCREST trials, the mean change in body weight for asenapine was 0.8 kg. The proportion of subjects with clinically significant weight gain (≥ 7 % weight gain from baseline at endpoint) in the short-term bipolar mania trials was 6.5% for asenapine compared to 0.6% for placebo.
About Bipolar I Disorder
Bipolar I disorder (also known as manic depression) is a chronic, episodic illness characterized by mania (episodes of elevated moods, extreme irritability, decreased sleep and increased energy), depression (overwhelming feelings of sadness, suicidal thoughts), or a combination of both.
Important Safety Information
Elderly patients with dementia-related psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic substances are at an increased risk of death. Sycrest is not approved for the treatment of patients with dementia-related psychosis and is not recommended for use in this particular group of patients.
Neuroleptic Malignant Syndrome
Neuroleptic Malignant Syndrome (NMS), characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels, has been reported to occur with antipsychotics, including asenapine. Additional clinical signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs and symptoms indicative of NMS Sycrest must be discontinued.
Seizures
In clinical trials, cases of seizure were occasionally reported during treatment with asenapine. Therefore, Sycrest should be used with caution in patients who have a history of seizure disorder or have conditions associated with seizures.
Suicide
The possibility of a suicide attempt is inherent in psychotic illnesses and bipolar disorder and close supervision of high-risk patients should accompany treatment.
Orthostatic hypotension
Asenapine may induce orthostatic hypotension and syncope, especially early in treatment, probably reflecting its О±1-adrenergic antagonist properties. Elderly patients are particularly at risk for experiencing orthostatic hypotension. In clinical trials, cases of syncope were occasionally reported during treatment with Sycrest. Sycrest should be used with caution in elderly patients and in patients with known cardiovascular disease (e.g., heart failure, myocardial infarction or ischemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (e.g., dehydration and hypovolemia).
Tardive dyskinesia
Medicinal products with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia characterised by rhythmical, involuntary movements, predominantly of the tongue and/or face. In clinical trials, cases of tardive dyskinesia were occasionally reported during treatment with asenapine. The onset of extrapyramidal symptoms is a risk factor for tardive dyskinesia. If signs and symptoms of tardive dyskinesia appear in a patient on Sycrest, discontinuation of treatment should be considered.
Hyperprolactinaemia
Increases in prolactin levels were observed in some patients with Sycrest. In clinical trials, there were few adverse reactions related to abnormal prolactin levels reported.
QT interval
Clinically relevant QT prolongation does not appear to be associated with asenapine. Caution should be exercised when Sycrest is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other medicinal products thought to prolong the QT interval.
Hyperglycaemia and diabetes mellitus
Hyperglycaemia or exacerbation of pre-existing diabetes has occasionally been reported during treatment with asenapine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia or bipolar disorder and the increasing incidence of diabetes mellitus in the general population. Appropriate clinical monitoring is advisable in diabetic patients and in patients with risk factors for the development of diabetes mellitus.
Dysphagia
Esophageal dysmotility and aspiration have been associated with antipsychotic treatment. Cases of dysphagia were occasionally reported in patients treated with Sycrest.
Body temperature regulation
Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic medicines. From the clinical trials, it is concluded that clinically relevant body temperature dysregulation does not appear to be associated with asenapine. Appropriate care is advised when prescribing Sycrest for patients who will be experiencing conditions that may contribute to an elevation in core body temperature, e.g. exercising strenuously, exposure to extreme heat, receiving concomitant medicinal products with anticholinergic activity or being subject to dehydration.
Patients with severe hepatic impairment
Asenapine exposure is increased 7-fold in patients with severe hepatic impairment (Child-Pugh C). Therefore, Sycrest is not recommended in such patients.
Parkinson's disease and dementia with Lewy bodies
Physicians should weigh the risks versus the benefits when prescribing antipsychotic medicinal products, including Sycrest, to patients with Parkinson's disease or dementia with Lewy Bodies (DLB) since both groups may be at increased risk of Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotics. Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms.
Drug Interactions
Caution should be used when asenapine is taken in combination with other centrally acting medicinal products. Patients should be advised to avoid alcohol while taking SYCREST. Additionally, SYCREST should be co-adminsitered cautiously with fluvoxamine (a CYP1A2 inhibitor) and with medicinal products that are both substrates and inhibitors of CYP2D6 (e.g., paroxetine).
For full prescribing information, please refer to the Summary of Product Characteristics.
Source:
MSD
View drug information on Saphris.
Комментариев нет:
Отправить комментарий