Milnacipran | Proof of Concept Trials

Development Status | Phase II Results | Phase III Trials

Cypress is developing milnacipran for the treatment of FM. Milnacipran is a unique dual-reuptake inhibitor, which preferentially blocks the reuptake of norepinephrine with higher potency than serotonin, two neurotransmitters known to play an essential role in regulating pain and mood. Milnacipran acts by increasing norepinephrine and serotonin, chemicals in the brain that are thought to be involved in controlling "centrally mediated pain" – that is, pain that originates at the central nervous system level, as opposed to pain that is caused by an injury, such as a cut or an arthritic swollen joint.

Extensive preclinical and clinical data support the primacy of norepinephrine in central analgesia.  Milnacipran affects the reuptake of norepinephrine and serotonin in 3:1 ratio – that is, it increases norepinephrine more than it does serotonin.  This profile of milnacipran is unique among commercially available reuptake inhibitors.  In addition, milnacipran does not interact with receptors that are responsible for side effects associated with some other therapies (for example, drugs affecting histaminergic receptors can cause weight gain, whereas affecting muscarinic receptors can cause drowsiness).  Lastly, based on how milnacipran is metabolized, it does not interact with many other commonly prescribed drugs.

Milnacipran has been approved for a non-pain condition in over 50 countries, with real-world commercial experience outside the U.S. for 10 years. Milnacipran has not been approved in the United States for any indication, and we are the first company conducting clinical trials of milnacipran in the United States for FM. Milnacipran is jointly being developed for fibromyalgia in the United States market by Forest and its licensor, Cypress Bioscience, Inc. Milnacipran was originally developed by and is sold outside of the U.S. by Pierre Fabre Medicament.