Empatic™ is Orexigen’s second late-stage, investigational medication for weight loss. It is a fixed-dose combination of a proprietary formulation of zonisamide sustained release (SR) and bupropion SR.
Bupropion is thought to increase the level of dopamine activity at specific receptors in the brain, which appears to lead to a reduction in appetite and increase in energy expenditure by increasing activity of POMC neurons. Zonisamide increases monoamines, which are thought to suppress NPY/AgRP neurons and further stimulates the POMC neurons.
In a Phase 2b clinical trial of Empatic 360 mg, patients completing 24 weeks of therapy, lost 9.9% of their baseline body weight, or 22 pounds, compared to 1.7% for placebo patients (p<0.001). Additionally, 82.6% of these patients lost at least 5% of their baseline body weight and 47.7% lost at least 10% of their baseline body weight compared to 18.9% and 5.7% of placebo patients, respectively (p<0.001 for both).
The most commonly reported adverse events for all Empatic patients were headache, insomnia and nausea.
The most common adverse events leading to discontinuation were insomnia, headache and urticaria (hives).
Phase 2 testing of Empatic has been completed. Orexigen is communicating with the FDA regarding Empatic Phase 3 clinical development plans.