(dailyRx News) Forest Laboratories, Inc. and Cypress Bioscience, Inc. have announced that Savella (milnacipran HCl) was approved by the U.S. Food and Drug Administration to manage fibromyalgia.
Savella is a selective serotonin and norepinephrine reuptake inhibitor (SNRI). Its safety and efficacy were established in two pivotal phase 3 clinical trials involving over 2,000 patients with fibromyalgia. The studies showed that Savella doses of 100 mg a day and 200 mg a day demonstrated statistically significant and clinically meaningful concurrent improvements in pain, patient global assessment and physical function. The companies expect Savella to be available in pharmacies by March 2009.
Fibromyalgia is a chronic condition characterized by widespread pain and decreased physical function. It afflicts as many as 6 million people in the U.S.
"Fibromyalgia is a complicated chronic pain condition, so it is important that physicians and patients have access to treatments that have been shown to help manage the symptoms that define the experience of fibromyalgia," said Dr. Daniel Clauw, professor of anesthesiology and medicine (rheumatology) at the University of Michigan. "The introduction of Savella is important because it is the first drug approved to treat the symptoms of fibromyalgia using a composite responder analysis."
"Savella is the product of a unique clinical development program, one that considered a patient to be a responder to therapy only if they demonstrated concurrent clinically significant changes in multiple aspects of their fibromyalgia, including pain, patient global assessment and physical function," said Jay D. Kranzler, M.D., Ph.D., chairman and CEO of Cypress Bioscience.
Although the exact mechanism by which Savella improves the symptoms of fibromyalgia is unknown, some researchers believe that abnormalities in certain brain neurotransmitters may be central to fibromyalgia. Savella blocks the reuptake of both norepinephrine and serotonin, with greater selectivity for the inhibition of norepinephrine reuptake in vitro. This may be the mechanism by which Savella acts to improve the symptoms of fibromyalgia.
The clinical development program for Savella was unique in its use of a composite responder analysis as the primary endpoint. This endpoint required individual patients to demonstrate concurrent improvement to multiple validated measures, including pain (visual analog scale), patient global assessment (patient global impression of change) and physical function (Short Form-36 Physical Component Summary).
The efficacy of Savella was established in two pivotal phase 3 clinical trials involving 2,084 treated patients (1,460 Savella, 624 placebo), which showed that Savella demonstrated clinically significant improvements compared to placebo in treating fibromyalgia. The first study lasted six months and the second study lasted three months.
In both studies, a greater proportion of patients in the Savella treatment arms (100 mg/day and 200 mg/day) as compared with placebo treatment, at three months, experienced at least a 30-percent 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, physical function and patient global assessment.
In both studies, 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 these studies.
The most frequently occurring adverse reaction was nausea. Other common adverse reactions reported in these clinical trials were constipation, hot flush, hyperhidrosis, vomiting, palpitations, heart rate increased, dry mouth and hypertension (high blood pressure). The majority of adverse reactions reported were mild to moderate in nature.
Important Safety Information About Savella
Savella is an (SNRI, similar to some drugs used to treat 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 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. 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 of an MAOI or in patients with uncontrolled narrow-angle glaucoma.
Development of a potentially life-threatening serotonin syndrome may occur with agents that inhibit serotonin reuptake, including Savella, particularly with concomitant use of serotonergic drugs (including triptans and tramadol) and with drugs that impair metabolism of serotonin (including MAOIs). The concomitant use of Savella with serotonin precursors is not recommended.
Blood pressure and heart rate should be monitored prior to initiating treatment with Savella and periodically throughout treatment. SNRIs, including Savella, have been associated with reports of increases in blood pressure and heart rate. Preexisting 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. 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 a seizure disorder, mania or controlled narrow-angle glaucoma.
Savella has been associated with mild elevations of ALT and AST. Rarely, fulminant hepatitis has 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.
Savella should ordinarily not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease.
As with other SNRIs and SSRIs (selective serotonin reuptake inhibitors), 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. 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 clotting.
Men with a history of obstructive uropathies may experience higher rates of genitourinary adverse events.
Savella is unlikely to be involved in clinically significant pharmacokinetic drug interactions. Pharmacodynamic interactions of Savella with other drugs can occur.
Savella contains FD&C Yellow No. 5, which may cause allergic-type reactions in susceptible persons.