BUDAPEST, Hungary, April 16, 2019 /PRNewswire/ -- On 6-9 April 2019, during the 27th psychiatry congress of the European Psychiatric Association (EPA) in Warsaw, Poland new post hoc analyses of cariprazine studies in schizophrenia were presented. According to the presentations other atypical antipsychotics with dopamine D2 antagonist or partial agonist properties don't have cognitive improving features and are not able to occupy dopamine D3 receptors (in vivo) like cariprazine was proven. It was also shown during an oral presentation that cariprazine was not just well tolerated in patients and was proved to be metabolically neutral, but also possess favorable weight gain side effect profile, which is one of the most important issues for patients treated with antipsychotics. The importance and the different possibilities of patient functioning, and real life experiences with cariprazine treatments were also presented at the congress.
The chronic brain disorder schizophrenia contains positive, negative and mood symptoms, as well as cognitive impairment. The illness affects about 1% of the population meaning that potentially an estimated 5 million people struggle with this illness in the EU. Negative symptoms of schizophrenia affect up to 60% of patients depending on the reference used and have a significant impact on their daily function.
Antipsychotics have been effective in the treatment of positive symptoms for decades, but treatment of negative symptoms remains a huge clinical challenge and a major unmet medical need. According to the results of different post hoc analyses and clinical researches, cariprazine seems to be an adequate answer to these challenges.
Data from non-clinical in vitro receptor binding studies, in vivo animal behavioural studies, human PET studies in patient with schizophrenia and the clinical trials were analysed and compared to provide evidence that the D3 receptor occupancy correlate with the improvement of cognitive symptoms of schizophrenia. In vivo animal studies showed that cariprazine has pro-cognitive effect. The studies confirmed that the dopamine D3 receptor in vivo activity of cariprazine may strongly be involved in its cognitive improving properties. Other atypical antipsychotics with dopamine D2 antagonist (e.g. risperidone) or partial agonist (aripiprazole and brexpiprazole) properties, but with negligible in vivo D3 activity don't have such cognitive improving features.
Antipsychotics have been a meaningful help for millions of patients with schizophrenia for decades, but due to the unfavourable metabolic side effects and the massive weight gain experienced in case of various antipsychotics, finding the right therapy for these patients is critical. Based on the four short term and four long term studies, cariprazine was metabolically neutral and well tolerated, with very low unfavourable metabolic changes during treatment. According to these Richter's studies the mean weight increase over short term treatment was 0.9kg with cariprazine and 0.3kg with placebo, and on long-term treatment it was only 0.5kg in the cariprazine group. Compared to other antipsychotics, the minimal weight gain effect observed with cariprazine could be one of the most important part of the favourable side effect profile of the medicine.
The measurement of the effectiveness of CNS medicines might have been a controversial issue for decades, but the Positive and Negative Syndrome Scale (PANSS) is the most widely-used standardized instrument for assessing symptom severity in clinical trials of schizophrenia. So far there were no analysis investigating the clinically minimally important difference for predominant negative symptoms of schizophrenia. Depending on the underlying concept, different methods lead to different results for the minimally clinically important difference (MCID) in patients with predominant negative symptoms. The Leucht analyses (2005. Schizophr Res 79) conclude that while a 50% PANSS total score reduction is relevant for acutely ill patients, in treatment refractory patients a smaller, 20%-25% reduction might be clinically important. Richter's Clinical Global Impression Improvement (CGI-I) based results show that in the predominantly negative symptom population an even smaller (8%-14%) change from baseline is already considered a clinically important difference.
Improving patient functioning in schizophrenia is one of the most important aspects of all kind of CNS illness treatments. With the educational financial support provided by Gedeon Richter and Recordati, a symposium chaired by Prof. István Bitter was hold at EPA, fully dedicated to this issue.
The impact of negative symptoms on patient functioning, the mechanism of action of cariprazine and some real life experiences in connection with the cariprazine treatment were presented at the symposium by prestigious experts of these topics.
Cariprazine is marketed under the brand name Vraylar in the US for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder and currently under FDA review in bipolar depression. In EU it was licensed for schizophrenia in 2017 by EMA under the brand name Reagila and has already been marketed in more than 10 European countries with reimbursement. In Western Europe Recordati, while in Central and Eastern Europe, Russia and CIS countries Gedeon Richter Plc is responsible for the commercialization. Subsequent European launches are expected during the course of 2019.
The 3 cariprazine scientific posters from the EPA are available on:
Cariprazine, a potent dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors, is approved in the EU for the treatment of schizophrenia in adults under the Brand Name Reagila® and in the US for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder under the Brand Name Vraylar®. In addition, cariprazine is under review by FDA for the treatment of bipolar depression and being investigated in late-stage clinical studies as adjunctive treatment for major depressive disorder in adults. Cariprazine is protected by a composition-of-matter patent that expires in 2029 in most of the major markets. Cariprazine was discovered by Gedeon Richter Plc. and is licensed to Allergan in North-America and to Recordati SpA in Western European Countries.
Gedeon Richter Plc. (www.richter.hu) headquartered in Budapest/Hungary, is a major pharmaceutical company in Central Eastern Europe, with an expanding direct presence in Western Europe, in China and in Latin America. Having reached a market capitalization of EUR 3.2 billion (USD 3.6 billion) by the end of 2018, Richter's consolidated sales were approximately EUR 1.4 billion (USD 1.6 billion) during the same year. The product portfolio of Richter covers many important therapeutic areas, including Women's Healthcare, Central Nervous System and Cardiovascular areas. Having the largest R&D unit in Central Eastern Europe, Richter's original research activity focuses on CNS disorders. With its widely acknowledged steroid chemistry expertise, Richter is a significant player in the Women's Healthcare field worldwide. Richter is also active in biosimilar product development.
Recordati, established in 1926, is an international pharmaceutical group, listed on the Italian Stock Exchange (Reuters RECI.MI, Bloomberg REC IM, ISIN IT 0003828271), with a total staff of more than 4,100, dedicated to the research, development, manufacturing and marketing of pharmaceuticals. Headquartered in Milan, Italy, Recordati has operations throughout the whole of Europe, including Russia, Turkey, North Africa, the United States of America, Canada, Mexico, some South American countries, Japan and Australia. An efficient field force of medical representatives promotes a wide range of innovative pharmaceuticals, both proprietary and under license, in a number of therapeutic areas including a specialized business dedicated to treatments for rare diseases. Recordati is a partner of choice for new product licenses for its territories. Recordati is committed to the research and development of new specialties with a focus on treatments for rare diseases. Consolidated revenue for 2018 was € 1,352.2 million, operating income was € 442.2 million and net income was € 312.4 million.