Forest Laboratories High Dose of Schizophrenia Drug Doesn't Meet Goal
NEW YORK and BUDAPEST, Hungary, Oct. 15 -- Forest Laboratories and Gedeon Richter today announced preliminary top-line results from a U.S. conducted randomized, double-blind, three-arm placebo-controlled study of RGH-188, a novel antipsychotic, in 389 schizophrenia patients. The protocol-specified primary endpoint was change from baseline to Week 6 on the Positive and Negative Syndrome Scale (PANSS) and RGH-188 demonstrated a nominally statistically significant (i.e., not adjusted for multiple comparisons) therapeutic effect compared to placebo in the treatment of schizophrenia in the low dose arm and a numerical improvement compared to placebo in the high dose arm that did not reach nominal statistical significance. At this time the companies have only been able to review top-line results and further analyses will be completed in the coming weeks to examine the results in greater detail.
Trial Design and Preliminary Study Results
Following a no-drug washout period of up to 7 days, patients (N=389) were randomized to one of three treatment groups: placebo, RGH-188 low dose (1.5- 4.5 mg/day) or RGH-188 high dose (6-12 mg/day). The double-blind treatment period lasted 6 weeks. Patients were hospitalized throughout screening and for at least the first 21 days following the initiation of double-blind study medication. Following completion of the 6 weeks of double-blind treatment, patients were followed up for safety assessments for an additional 4 weeks. The study was conducted entirely in the United States.
This was a flexible fixed dosage range study in which patients received 1 to 3 capsules administered as a single daily dose at bedtime. All patients started with 1 capsule (placebo or RGH-188 1.5 mg). The daily dose could be increased to 3 capsules given once daily by Day 5 or thereafter depending on patient response and tolerability based on investigator's judgment. For patients randomized to RGH-188 low dose (1.5-4.5 mg/day) group, the maximum dose of 4.5 mg per day could be reached by Day 5, whereas for patients randomized to RGH-188 high dose (6-12 mg/day) group, the maximum dose of 12 mg per day could be reached by Day 9. Following a dose increase, the dose could be decreased if there were any tolerability problems. Any increases or decreases were to be done in increments or decrements of one capsule.
RGH-188 was generally well tolerated and overall premature discontinuation rates (all causes including adverse event related) were 47% for patients receiving low dose of RGH-188, 46% for patients receiving high dose RGH-188, and 47% for patients receiving placebo.
Future Development Plans
Based on the initial positive results for one of the active dosing arms and subject to a complete review of the full study results for the just completed trial, the Companies intend to continue the development of RGH-188 as a treatment for schizophrenia and will determine the appropriate development activities over the coming months.
Additionally, the Companies expect to receive topline results for the proof of concept study for RGH-188 in bipolar mania in by the middle of calendar 2008.
RGH-188 (INN: cariprazine) discovered by researchers at Gedeon Richter, is a novel antipsychotic which preferentially binds to D3 receptors and acts as a dopamine system stabilizer.
About Forest Laboratories and Its Products
Forest Laboratories (www.frx.com) is a US-based pharmaceutical company dedicated to identifying, developing and delivering products that make a positive difference in peoples' lives. Forest Laboratories' growing product line includes LexaproÂ® (escitalopram oxalate), an SSRI indicated for adults for the initial and maintenance treatment of major depressive disorder and generalized anxiety disorder; NamendaÂ® (memantine HCl), an N-methyl D-aspartate (NMDA)-receptor antagonist indicated for the treatment of moderate to severe Alzheimer's disease; BenicarÂ®* (olmesartan medoxomil), an angiotensin receptor blocker, and Benicar* HCTÂ® (olmesartan medoxomil-hydrochlorothiazide), an angiotensin receptor blocker and diuretic combination product, each indicated for the treatment of hypertension; and CampralÂ®* (acamprosate calcium), indicated in combination with psychosocial support for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation.
*Benicar is a registered trademark of Daiichi Sankyo, Inc., and Campral is a registered trademark of Merck Sante s.a.s., subsidiary of Merck KGaA, Darmstadt, Germany.
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 approximately 1 billion USD in 2006, and 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, 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 gynaecological field worldwide. 16 % 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 CNS disorders. 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 16 ongoing projects including four compounds which are in either in Phase I or Phase II clinical trials.
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 the Forest Laboratories' SEC reports, including the Company's Annual Report on Form 10-K for the fiscal year ended March 31, 2007.