TD-9855 · program
Ampreloxetine for Fibromyalgia
Indications for TD-9855: Multiple System Atrophy · Discontinued Fibromyalgia · Discontinued Attention-deficit/hyperactivity disorder · Discontinued
TD-9855 (ampreloxetine), as a norepinephrine and serotonin reuptake inhibitor, in fibromyalgia. A Phase 2 randomized, double-blind, placebo-controlled study (NCT01693692, n=392; 5 mg or 20 mg once daily up to 6 weeks) met its primary endpoint (change in average daily pain) at 20 mg, with significant FIQ and PGIC secondary benefits, while 5 mg missed; both doses were generally well tolerated (reported 2014-04-30). The program never advanced to Phase 3; the molecule was repositioned to neurogenic orthostatic hypotension, and Theravance wound down its R&D function in March 2026. No explicit fibromyalgia discontinuation announcement was found.
Development timeline
- Inferred: Theravance announced complete wind-down of its R&D organization and the ampreloxetine program. Upper bound — de facto inactivity dates from ~2014.↗
- metTD-9855 20 mg met the primary endpoint (change in average daily pain score) and FIQ/PGIC secondaries vs placebo in fibromyalgia; 5 mg missed the primary.↗
- NCT01693692 started (month precision per CT.gov).
Readouts
- 2014-04-30ReportedTopline datametNCT01693692
TD-9855 20 mg met the primary endpoint (change in average daily pain score) and FIQ/PGIC secondaries vs placebo in fibromyalgia; 5 mg missed the primary. ↗
Clinical trials in Fibromyalgia
NCT016936920092Phase 2Completedn=392
Phase 2 Study of TD-9855 to Treat Fibromyalgia
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Ampreloxetine oral once-daily ADHD Phase 2: 5 mg once daily, or 10 mg titrated to 20 mg once daily (oral capsules), 42 days. Fibromyalgia Phase 2: 5 mg or 20 mg once daily up to 6 weeks. nOH Phase 2 (NCT02705755): escalating doses over 5 days, median 10 mg once daily over 20 weeks. CYPRESS dose not verified from an opened source. | Oral | Once daily | — |
Mechanism of action
Inhibitor of the norepinephrine transporter (NET, SLC6A2) with lesser serotonin transporter (SERT, SLC6A4) activity and weak dopamine transporter activity. Human recombinant transporter binding: pKi 8.8 (NET), 8.5 (SERT), 6.7 (DAT); uptake inhibition pIC50 8.6 (NET), 8.0 (SERT), 6.8 (DAT), i.e. 4- to 10-fold functional selectivity for NET. Brain-penetrant: human PET estimated NET plasma EC50 1.21 ng/mL with projected >75% steady-state NET occupancy above 4 mg, and ~25% SERT occupancy after 20 mg. Originally positioned as an NSRI for CNS indications (ADHD, fibromyalgia); in nOH it is described as a selective NRI whose rationale is peripheral — blocking NE reuptake at residual postganglionic sympathetic neurons, which are relatively spared in MSA, to raise vasoconstrictor tone (plasma NE +71%, DHPG -22% on treatment).
| Target | Action | Affinity |
|---|---|---|
| NETprimarySLC6A2 | Reuptake inhibitor | pKi 8.8ⓘ |
| SERTSLC6A4 | Reuptake inhibitor | pKi 8.5ⓘ |
← Full TD-9855 compound page (identity, identifiers, all indications)
Sources
- Lo A et al. Pharmacokinetics and pharmacodynamics of ampreloxetine, a novel, selective norepinephrine reuptake inhibitor, in symptomatic nOH. Clin Auton Res 2021;31(3):395-403 — Clinical Autonomic Research / PubMed
- NCT01693692 — Study 0092 Phase 2 of TD-9855 in fibromyalgia — ClinicalTrials.gov (U.S. National Library of Medicine)
- Smith JA et al. Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor. Int J Neuropsychopharmacol 2015;18(2):pyu027 — Int J Neuropsychopharmacol (OUP) via PubMed Central
- Theravance Biopharma 8-K Ex.99.1 (2026-03-03): Phase 3 CYPRESS study did not meet primary endpoint; ampreloxetine program wound down — Theravance Biopharma / SEC EDGAR
- Theravance reports positive Phase II trial results of fibromyalgia drug candidate TD-9855 (2014-04-30) — Clinical Trials Arena