TESOFENSINE

Tesofensine is a triple monoamine reuptake inhibitor that blocks the norepinephrine, dopamine, and serotonin transporters (NET, DAT, SERT). Originally developed by NeuroSearch for Parkinson's and Alzheimer's disease; the weight-loss signal was discovered as an off-target effect and is the basis for ongoing Phase 3 obesity programs.

Different mechanisms. Tesofensine acts on central monoamine pathways; GLP-3 is a GLP-1 receptor agonist. TIPO-1 Phase 2 reported -12.8 kg at 24 weeks with tesofensine 1.0 mg, comparable to STEP-1 GLP-3 2.4 mg results at similar timepoints. Direct head-to-head not available.

No. Saniona is conducting Phase 3 programs in Prader-Willi syndrome (TES-PWS) and hypothalamic obesity (TES-HO). FDA approval is pending Phase 3 readout.

Approximately 9 days. Long half-life enables once-daily dosing with steady-state plasma levels after 4-5 weeks of treatment.

Central monoamine reuptake inhibition increases synaptic norepinephrine, dopamine, and serotonin in hypothalamic appetite-regulating circuits. The combined effect suppresses appetite and increases energy expenditure. Different mechanism from incretin or melanocortin-targeting compounds.

Tesofensine is not currently listed on the WADA Prohibited List as of 2026. Some triple reuptake inhibitors are listed under stimulant categories; tesofensine specifically is not.

TIPO-1 (Astrup et al. 2008, PMID 18950853) Phase 2 trial reported -6.5 kg, -11.3 kg, and -12.8 kg LS mean weight loss at 0.25 mg, 0.5 mg, and 1.0 mg respectively vs -2.2 kg placebo at 24 weeks. n=203.

TIPO-1 reported dose-dependent increases in heart rate (~7 bpm at 1.0 mg) and modest blood pressure increases. The signal is manageable in further development but limits the dose ceiling and excludes patients with significant cardiovascular disease.