Forest Laboratories, Inc. (FRX) and Gedeon Richter Plc Announce Positive Phase II Results with the Investigational Antipsychotic Cariprazine
NEW YORK and BUDAPEST, Hungary, Sept. 30 /PRNewswire-FirstCall/ -- Forest Laboratories, Inc. (NYSE: FRX - News) and Gedeon Richter Plc today announced preliminary top-line results from a phase II clinical trial of cariprazine (RGH-188), an investigational antipsychotic, in patients with acute mania associated with bipolar I disorder. For the primary endpoint, the Young Mania Rating Scale (YMRS), the data showed that patients with acute manic episodes treated with cariprazine experienced significant symptom improvement compared to placebo patients within the first week of treatment and at each subsequent time point studied. Further analyses of the data will be completed in the coming weeks. Cariprazine is also currently being investigated in clinical studies in schizophrenia.
"These exciting preliminary results in patients with bipolar mania demonstrate the potential of cariprazine as a novel antipsychotic agent," stated Marco Taglietti, M.D., Executive Vice President and Chief Medical Officer, Forest Laboratories, Inc. "Therefore, we will continue to investigate and characterize the therapeutic benefits of cariprazine, a unique molecule with high selectivity for the D3 versus the D2 dopamine receptors.
"Dopamine system stabilizer cariprazine clearly proved its effect in this study," commented Zsolt Szombathelyi, M.D., Research Director of Gedeon Richter Plc. "The result confirms Richter's CNS research concept and the clinical opportunity of a dual acting D3/D2 compound."
About the Study
The phase II double-blind, placebo-controlled, flexible-dose study evaluated the safety, efficacy and tolerability of cariprazine monotherapy in patients with acute mania associated with bipolar I disorder. During the five week study, 236 men and women 18 to 65 years of age meeting the DSM-IV criteria for bipolar I disorder were randomized and received at least one dose of either cariprazine, 3-12 mg/day (N=118), or placebo (N=118). Following a four day, no treatment wash out period, patients were given 1-4 capsules daily (cariprazine or placebo). The treatment period lasted three weeks followed by safety assessments for an additional two weeks. Patients were hospitalized throughout screening and for at least the first 14 days following the initiation of treatment.
The primary, protocol-specified, endpoint was change from baseline to Week 3 on the YMRS, using last observation carried forward (LOCF) analyses. The YMRS is a comprehensive, clinician-rated instrument used to assess the severity of mania in bipolar patients, including such parameters as elevated mood, increased motor activity energy, sleep and irritability. Statistically significant improvement was noted in patients receiving cariprazine (3-12mg/day) relative to patients receiving placebo on the YMRS scale (-15.0 cariprazine vs. -8.9 placebo, p < 0.0001) by the LOCF analysis. Statistically significant improvement in the YMRS scale was also noted in the mixed model repeated measure (MMRM) analysis (-15.5 cariprazine vs. -8.5 placebo, p < 0.0001) and the observed-cases (OC) analysis (-19.1 cariprazine vs. -13.6 placebo, p < 0.0001).
Overall premature discontinuation rates (all causes, including adverse event related) were 36 % for patients receiving cariprazine and 38% for patients receiving placebo. The most common adverse events observed in the study were headache, extrapyramidal disorders, nausea, akathisia and constipation. Cariprazine was generally well tolerated with discontinuations due to adverse events observed in 14% of the cariprazine group and 10% of the placebo group.
Cariprazine, discovered by researchers at Gedeon Richter, is an orally active, potent D3/D2 functional antagonist that preferentially binds to D3 receptors and acts as a dopamine system stabilizer. In addition, cariprazine has a low potency at other receptor sites, such as 5-HT2C, histamine H1, and adrenergic receptor sites, which have been associated with adverse events.
About Acute Mania in Bipolar Disorder
Bipolar disorder, also known as manic depression, is a serious medical illness most commonly characterized by extreme shifts in mood ranging from crippling "lows" (depression) to intense "highs" (mania).(1) During the manic phase of the illness, the person may feel euphoric or extremely irritable.(1) Other signs and symptoms include a high energy level, racing thoughts, impaired judgment, and denial that anything is wrong.(1) A manic episode is diagnosed if symptoms occur in combination most of the day, nearly every day, for one week or longer. (1)
About Forest Laboratories
Forest Laboratories (NYSE: FRX - News) is a U.S.-based pharmaceutical company with a long track record of building partnerships and developing and marketing products that make a positive difference in people's lives. In addition to its well-established franchises in therapeutic areas of the central nervous and cardiovascular systems, Forest's current pipeline includes product candidates in all stages of development and across a wide range of therapeutic areas. The company is headquartered in New York, NY. To learn more about Forest Laboratories, visit www.FRX.com.
Except for the historical information contained herein, this release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements involve a number of risks and uncertainties, including the difficulty of predicting FDA approvals, the acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, the timely development and launch of new products, and the risk factors listed from time to time in Forest Laboratories' Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and any subsequent SEC filings.
About Gedeon Richter Plc.
Gedeon Richter, (www.richter.hu) headquartered in Budapest/Hungary, is a major pharmaceutical company in Hungary and one of the largest in Central Eastern Europe, with consolidated sales of 1.2 billion USD in 2007, and 3.4 billion USD market capitalisation. The company was founded in 1901. Gedeon Richter plays the role of a regional multinational company in Central Eastern Europe and in the CIS, and has a growing presence through its commercial subsidiaries in key EU countries, and the USA. The company has a worldwide presence through its representative offices and subsidiaries in 30 countries. It has manufacturing sites in Hungary, Russia , Romania , Poland , India and a recently acquired German R&D biotechnology production facility. The product portfolio of the company covers almost all important therapeutic areas. With its widely acknowledged steroid chemistry expertise the company is a significant player in the gynecological field worldwide. 14 % of the company's revenue results from original drug research and development activity. The company has the largest R&D unit in Central Eastern Europe focusing exclusively on the field of neurology and psychiatry. Following reorganization of the proprietary R&D in 2000, main clinical targets are schizophrenia, anxiety and chronic pain. Complementing its own preclinical excellence R&D collaboration agreements were signed with Mitsubishi Pharma Corporation (Japan) and Forest Laboratories in 2004 and 2005. The company has an original R&D portfolio with 17 ongoing projects including four compounds which are in either in Phase I or Phase II clinical trials.
1. National Institute of Mental Health. "Bipolar Disorder." Available at http://www.nimh.nih.gov/health/publications/bipolar-disorder/complete- publication.shtml. Accessed: September 24, 2008.
Source: Gedeon Richter Plc; Forest Laboratories, Inc.