Forest Laboratories and Cypress Bioscience Announce Study Shows Patients Treated with Savella Experience Improvements in Pain and Physical Function
Phase III Data to be Presented at American College of Rheumatology Annual Meeting Further Demonstrate Efficacy and Safety of Savella for the Management of Fibromyalgia
NEW YORK & SAN DIEGO--(BUSINESS WIRE)--Oct 17, 2009 - Forest Laboratories, Inc. (NYSE: FRX) and Cypress Bioscience, Inc. (NASDAQ: CYPB) today announced that Savella® (milnacipran HCI) 100 mg/day (50 mg twice daily) demonstrated statistically significant and clinically meaningful concurrent improvements in pain, patient global assessment, and physical function, according to results from a large-scale, Phase III clinical trial that will be presented on Tuesday, October 20, 2009, at the American College of Rheumatology Annual Meeting in Philadelphia, PA. 100 mg/day is the recommended dose of Savella. Savella is a selective serotonin and norepinephrine dual reuptake inhibitor (SNRI) that was approved by the U.S. Food and Drug Administration (FDA) earlier this year for the management of fibromyalgia.
Fibromyalgia is a chronic condition characterized by widespread pain and decreased physical function, afflicting as many as six million people in the United States. The study showed statistically significant and clinically meaningful concurrent improvements in pain, patient global assessment, and physical function, among patients receiving Savella treatment of 100 mg/day, as compared to a placebo treatment group, when measured by patient-reported outcomes assessed in composite responder analyses. These results at the 100 mg/day dose are consistent with those of previous clinical trials that have demonstrated the safety and efficacy of Savella at doses of 100 mg/day and 200 mg/day.
"Fibromyalgia is a common, chronic pain disorder that can be associated with an array of debilitating symptoms, so it is important that treatments manage the multiple symptoms of fibromyalgia and improve function," said lead investigator, Lesley M. Arnold, MD, Professor of Psychiatry, University of Cincinnati College of Medicine.
This Phase III, double-blind, placebo-controlled trial of 1,025 fibromyalgia patients was designed to further evaluate the efficacy and tolerability of Savella 100 mg/day. Patients were randomized to receive Savella 100 mg/day (n=516) or placebo (n=509) and underwent four to six weeks of flexible dose escalation, followed by 12 weeks of stable-dose treatment followed by a two-week randomized, double-blind discontinuation phase.
This study, like other phase III fibromyalgia studies of Savella used a composite responder analysis as the primary endpoint. This endpoint required individual patients to demonstrate concurrent and clinically meaningful improvements in multiple domains using validated measures, including pain (visual analog scale), patient global assessment (patient global impression of change), and physical function (Short Form-36 Physical Component Summary).
In this study a greater proportion of patients in the Savella treatment arm (100 mg/day) as compared with placebo treatment, at 3 months, experienced at least a 30% reduction in pain from baseline and also rated themselves as "very much improved" or "much improved" based on the patient global assessment. In addition, a greater proportion of patients treated with Savella as compared with placebo treatment met the criteria for a treatment response as measured by concurrent improvements in pain, patient global assessment, and physical function. Some patients who rated themselves as globally "much" or "very much" improved experienced a decrease in pain as early as week 1 of treatment with a stable dose of Savella that persisted throughout the study.
“These data confirm the benefits of Savella in managing fibromyalgia,” said Dr. Marco Taglietti, President of Forest Research Institute. “Patients receiving Savella showed simultaneous improvements on multiple measures of fibromyalgia, including pain, patient global assessment, and physical function.”
Savella was generally well tolerated in the study. The most common treatment emergent adverse events observed during the placebo-controlled trial included nausea, headache, constipation, hot flush, dizziness, insomnia, hyperhidrosis, palpitations, fatigue, tachycardia, and hypertension. The majority of adverse reactions reported were mild to moderate in nature.
Overall premature discontinuation rates (all causes, including those related to adverse events) through the stable-dose treatment period of the trial were similar for patients receiving 100 mg/day of Savella and patients receiving placebo.
Savella was approved by the FDA on January 14, 2009, for the management of fibromyalgia, a chronic condition characterized by widespread pain and decreased physical function that afflicts as many as six million people in the United States. Savella is a dual-reuptake inhibitor that, in vitro, preferentially blocks the reuptake of norepinephrine with higher potency than for serotonin, two neurotransmitters thought to a play a central role in the symptoms of fibromyalgia. Savella is marketed by Forest and its licensor, Cypress Bioscience. Pierre Fabre, who originally developed and sells milnacipran outside the U.S., licensed the rights for North America to Cypress Bioscience.
Please visit www.savella.com for more information.
Important Safety Information
Savella is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), similar to some drugs used for the treatment of depression and other psychiatric disorders. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of such drugs in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on Savella should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior, especially during the initial few months of drug therapy or at times of dose changes, either increases or decreases. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Savella is not approved for use in the treatment of major depressive disorder. Savella is not approved for use in pediatric patients.
Savella is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) concomitantly or within 14 days of discontinuing treatment with an MAOI. There have been reports of serious, sometimes fatal, reactions in patients started on an MAOI who were receiving or had recently discontinued a serotonin reuptake inhibitor. At least 5 days should be allowed after stopping Savella before starting an MAOI.
Savella is contraindicated in patients with uncontrolled narrow-angle glaucoma and should be used with caution in patients with controlled narrow-angle glaucoma. In clinical trials, Savella was associated with an increased risk of mydriasis.
Warnings and Precautions
Prescriptions for Savella should be written for the smallest quantity of tablets, consistent with good patient management, in order to reduce the risk of overdose.
Development of a potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with SSRIs and SNRIs alone, including Savella, but particularly with concomitant use of serotonergic drugs (including triptans), drugs that impair metabolism of serotonin (including MAOIs), or antipsychotics or other dopamine antagonists. The management of these reactions should include immediate discontinuation of Savella and the concomitant agent and supportive symptomatic treatment. The concomitant use of Savella with serotonin precursors is not recommended.
SNRIs, including Savella, have been associated with cardiovascular effects, including cases of elevated blood pressure, requiring immediate treatment. In clinical trials, sustained increases in systolic and diastolic blood pressure occurred more frequently in Savella-treated patients compared to placebo. Among patients who were non-hypertensive at baseline, approximately twice as many patients receiving Savella, vs placebo, became hypertensive at the end of the study. Clinically significant increases in pulse (‰¥20 bpm) occurred more frequently in Savella-treated than placebo-treated patients. Blood pressure and heart rate should be monitored prior to initiating treatment with Savella and periodically throughout treatment. Pre-existing hypertension, tachyarrhythmias, and other cardiac diseases should be treated before starting therapy with Savella. Savella should be used with caution in patients with significant hypertension or cardiac disease. Concomitant use of Savella with drugs that increase blood pressure and pulse has not been evaluated, and such combinations should be used with caution. For patients who experience a sustained increase in blood pressure or heart rate while receiving Savella, either dose reduction or discontinuation should be considered.
Savella should be prescribed with caution in patients with a history of seizure disorder or mania.
Savella has been associated with mild elevations of ALT and AST (1 to 3 times the upper limit of normal). Rarely, reports of serious liver injury, including fulminant hepatitis, have been reported in patients treated with milnacipran. Savella should be discontinued in patients who develop jaundice or other evidence of liver dysfunction and should not be resumed unless another cause can be established.
As with other SNRIs and SSRIs, withdrawal symptoms have been observed following discontinuation of milnacipran. A gradual dose reduction is recommended.
Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Savella. Elderly patients may be at greater risk. Discontinuation should be considered for patients with symptomatic hyponatremia.
SSRIs and SNRIs, including Savella, may increase the risk of bleeding events. Patients should be cautioned regarding the risk of bleeding associated with concomitant use of Savella and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation.
Savella can affect urethral resistance and micturition. Caution is advised in the use of Savella in patients with a history of dysuria, notably in male patients with a history of obstructive uropathies as these patients may experience higher rates of genitourinary adverse events.
Savella should ordinarily not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease.
Use in Specific Populations
There are no adequate and well-controlled studies in pregnant women. Savella should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
In clinical trials, the most frequently occurring adverse reaction was nausea (37% vs 20% for placebo). The most commonly occurring adverse reactions (‰¥5% and greater than placebo) were headache (18% vs 14%), constipation (16% vs 4%), dizziness (10% vs 6%), insomnia (12% vs 10%), hot flush (12% vs 2%), hyperhidrosis (9% vs 2%), vomiting (7% vs 2%), palpitations (7% vs 2%), heart rate increased (6% vs 1%), dry mouth (5% vs 2%), and hypertension (5% vs 2%).
About Forest Laboratories
Forest Laboratories (NYSE: FRX) 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 Report on Form 10-Q, and any subsequent SEC filings.
About Cypress Bioscience
Cypress Bioscience, Inc. provides therapeutics and personalized medicine services, facilitating improved and individualized patient care. Cypress addresses the evolving needs of specialist physicians and their patients by identifying unmet medical needs in the areas of pain, rheumatology, and physical medicine and rehabilitation, including challenging disorders such as fibromyalgia and rheumatoid arthritis. This approach to improving patient care creates a unique partnership with physicians. Current products include Savella® (milnacipran HCI) and the Avise PGSM and Avise MCVSM therapeutic monitoring, diagnostic and prognostic tests for rheumatoid arthritis.
For more information about Cypress, please visit the Company's website at www.cypressbio.com.
This press release, as well as Cypress' SEC filings and website at www.cypressbio.com, contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements regarding the potential of Savella to treat fibromyalgia and the ability of Savella to provide meaningful improvements in pain, patient global assessment and physical function among patients being treated for fibromyalgia. Actual results could vary materially from those described as a result of a number of factors, including those set forth in Cypress' Annual Report on Form 10-K, its most recent Quarterly Report on Form 10-Q and any subsequent SEC filings and including, but limited to, that more detailed analysis of the trial results may not be favorable or may lead to different conclusions, that Savella's efficacy for treating fibromyalgia may be perceived differently among doctors, patients and third-party payors than the trial results and that Savella may not meet with market acceptance. These forward-looking statements speak only as of the date hereof and Cypress disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
About Pierre Fabre
Pierre Fabre group, France's second biggest independent pharmaceutical laboratory, achieved a turnover of 1.75 billion euros in 2008. Approximately 10,000 people including 1,400 in the research sector, are employed Its therapeutic are ethical products, healthcare products and dermocosmetics with the brands Avene, Ducray, A Derma, Galenic, Klorane and Rene Furterer. In 2008, Pierre Fabre Medicament dedicated 33% of its annual turnover to R&D in five main therapeutic directions: oncology, the Central Nervous System, cardiology, internal medicine/urology and dermatology.
To learn more about the Pierre Fabre group, visit www.pierre-fabre.com.
Contact: Forest Laboratories, Inc.
Frank J. Murdolo, 212-224-6714
Vice President - Investor Relations
Cypress Bioscience, Inc.
Mary Gieson, 858-452-2323
Posted: October 2009