Forest’s fibromyalgia drug Savella (milnacipran) can increase heart disease risk

Savella (milnacipran) by Forest Laboratories Inc.’s approval could be reconsidered by the US FDA in view of the data suggesting that the fibromyalgia drug has an increased risk of heart diseases.

Public Citizen, the consumer advocacy group, has urged US FDA to immediately recall Savella (milnacipran) from US market.

Savella (milnacipran) causes higher blood pressure and heart rate in its users. Savella (milnacipran) also leads to thoughts of suicide in patients who had normal blood pressure before they started taking the pill, Washington-based Public Citizen said in a letter to the U.S. Food and Drug Administration, quoting studies.

Savella patients had a very high risk – nearly triple -of developing hypertension compared to that of patients which received placebo, studies found.

Savella (milnacipran) was approved by US FDA to treat fibromyalgia in January 2009.

Savella (milnacipran) is the first drug approved only for fibromyalgia.

Savella generated sales of $15.4 million in the quarter ended Dec. 31, up 50% from the prior quarter, New York-based Forest said in a statement.

Savella (milnacipran) competes with Pfizer Inc.’s Lyrica.

Savella (milnacipran) was denied approval by European drug authorities in July last year,  pointing out that its benefits were marginal and didn’t outweigh the risks.

Savella (milnacipran) is not effective in treating pain, Public Citizen said.

Savella is a dual-reuptake inhibitor (also known as a serotonin-norepinephrine reuptake inhibitor, or SNRI) that preferentially blocks the reuptake of norepinephrine with higher potency than serotonin (in-vitro), 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.

Fibromyalgia is a chronic and debilitating condition characterized by widespread pain and decreased physical functioning.

Fibromyalgia is estimated to affect over 6 million Americans, according to the American College of Rheumatology.

Fibromyalgia is most often diagnosed in the primary care setting and is the second most commonly diagnosed condition in rheumatology clinics in the United States after osteoarthritis.

Despite the high prevalence and severity of this condition, there are limited treatment options specifically approved for fibromyalgia in the United States.

The efficacy of Savella was established in two US pivotal Phase III 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 was 6 months in duration and the second study was 3 months in duration.

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 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.

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, alerts Forest.

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 which 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. 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. 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.
Headquartered in New York, NY, Forest Laboratories is a U.S.-based pharmaceutical company which 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.

Cypress Bioscience, Inc. provides therapeutics and personalized medicine services in the areas of pain, rheumatology, and physical medicine and rehabilitation, including challenging disorders such as fibromyalgia and rheumatoid arthritis.