Gedeon Richter Plc.: Cariprazine Shows Favorable Safety Parameters and Efficacy in Reducing Schizophrenia Negative Symptoms Compared to Aripiprazole

BUDAPEST, Hungary, Oct. 10, 2018 /PRNewswire/ -- On 6-9 October 2018, during the 31th congress of European College of Neuropsychopharmacology (ECNP) in Barcelona, Spain, new post hoc analysis of cariprazine studies in negative symptoms of schizophrenia was presented. According to the presentations the hypothesis that negative and cognitive symptoms of schizophrenia can be improved by a compound with dopamine D3 effect in vivo and with balanced occupancy at dopamine D3 and D2 receptors has been confirmed. Cariprazine also showed significantly better improvement in the negative symptoms of schizophrenia compared to a widely used antipsychotic aripiprazole and also compared to placebo. In addition cariprazine proved to have a favorable safety parameter with small effect on weight and sexual functions.

The chronic brain disorder schizophrenia is comprising positive, negative, and mood symptoms, as well as cognitive impairment and affects about 1% of the population: 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. That means that within the European Union up to 3 million people can be suffering from the negative symptoms of this illness.

Antipsychotics are effective in the treatment of positive symptoms, but treatment of schizophrenia with negative symptoms remains a huge clinical challenge and a major unmet medical need. According to the results of different post hoc analysis and clinical researches, cariprazine seems to be an adequate answers to these challenges.

Based on a randomized, double-blind, 6 week, placebo and aripiprazole controlled study, as expected both cariprazine and aripripazole improved prominent positive symptoms with parallel improvement of secondary negative symptoms – with comparable efficacy. Based on a post hoc analysis the situation was different in case of patients with predominant negative symptoms: in these cases only cariprazine proved to be superior over placebo in the treatment of negative symptoms, so it definitely outperformed aripripazole.

As for the safety profile of cariprazine based on eight different phase 3 schizophrenia studies (2.048 CAR and 683 Placebo) it was proved to be generally safe and well tolerated. The most frequent adverse events were akathisia and EPS, which were mostly mild to moderate in intensity and rarely led to study discontinuation. Cariprazine is proved to be metabolically silent (metabolic parameters changed similarly to placebo) and had relatively small effects on weight, sedation and QT parameters. In addition the medicine does not cause hyperprolactinaemia and therefore causes little sexual dysfunction. Long-term treatment with antipsychotic agents is indicated for the vast majority of patients with schizophrenia. These drugs can be of great benefit for a wide range of symptoms, but treatment is associated with unpleasant adverse effects including weight gain, metabolic and cardiac abnormalities, extra pyramidal symptoms (EPS), hyperprolactinaemia and sexual dysfunctions. Therefore, the favorable safety profile of cariprazine means a significant comparative advantage.

Data from non-clinical in vitro receptor binding studies, in vivo animal behavioral studies, human PET studies in patient with schizophrenia and the clinical trial in predominant negative symptom patients were analyzed and compared to provide evidence how the D3 receptor occupancy can correlate with the improvement of negative and cognitive symptoms of schizophrenia. Detailed study results seems to confirm the hypothesis that negative and cognitive symptoms of schizophrenia can be improved indeed by a compound with dopamine D3 effect in vivo and with balanced occupancy at dopamine D3 and D2 receptors.

All in all the post hoc analyses presented at the conference, underlined that cariprazine can be a reliable and effective treatment possibility for patients with predominant negative symptoms, with a favorable safety profile.

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 already marketed in Germany, Sweden, Finland and England by Recordati who acquired the Western European commercialization rights of the product. Subsequent European launches are expected during the course of 2018 and 2019.

About Cariprazine

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 being investigated for the treatment of bipolar depression and as adjunctive treatment for major depressive disorder in adults. Cariprazine is protected by a composition-of-matter patent that expires in 2029. Cariprazine was discovered by Gedeon Richter Plc. and is licensed to Allergan in North-America and to Recordati SpA in Western European Countries.

About Richter

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. Richter's consolidated sales exceeded EUR 1.4 billion in 2017. 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.

About Recordati

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 in the main European countries, in Russia, other Central and Eastern European countries, Turkey, North Africa, the United States of America, Canada, Mexico and in some South American countries. 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 2017 was € 1.288 billion.