Small Molecule · NBI-1065845

Osavampator (NBI-1065845)

Phase 3Neurocrine Biosciences, Inc. (NBIX)

Selective AMPA-receptor positive allosteric modulator (formerly TAK-653) that potentiates glutamate-evoked AMPA currents with minimal intrinsic agonism. In Phase 3 as adjunctive therapy for major depressive disorder. Discovered by Takeda; licensed to Neurocrine in 2020.

Also known as: NBI-1065845, TAK-653, Osavampator

Data current as of

Key facts

Modality
Small molecule
Chemical class
pyrazinothiadiazine dioxide, sulfonamide, thiadiazine
Chemistry
Achiral
Mechanism
AMPA receptor (GluA1) PAM
Highest phase
Phase 3
Lead indication
Major depressive disorder
Developer
Neurocrine Biosciences, Inc. (NBIX)
Trials
3 tracked · 2 recruiting · 69 sites

Mechanism of action#

Selective AMPA-receptor positive allosteric modulator; potentiates glutamate-evoked AMPA currents by slowing desensitization, glutamate-dependently with minimal intrinsic agonism.

TargetActionAffinity
AMPA receptor (GluA1)primaryGRIA1PAMEC50 2.2 µMⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
Osavampator oral
1 mg or 3 mg once daily (Phase 2 SAVITRI); Phase 1 single doses 0.3-18 mg
OralOnce dailyt½ 40.2 h · Tmax 5 h

Development timeline#

20212022202320242025Phase 327 Jan 2025 — Partnership — Neurocrine–Takeda amend collaboration for osavampator (ex-Japan vs. Japan split)22 Jan 2025 — phase change — Phase 3 registrational program initiated (adjunctive MDD; five studies, three pivotal).12 Jun 2020 — Licensing deal — Neurocrine in-licenses osavampator (NBI-1065845 / TAK-653) from TakedaPhase 223 Apr 2024 — phase change — Positive Phase 2 SAVITRI topline; primary + secondary endpoints met at 1 mg.
Phase change Readout Event UpcomingHover a marker for details.
Phase 3Jun 2020 – Jan 2025
  1. PartnershipNeurocrine–Takeda amend collaboration for osavampator (ex-Japan vs. Japan split)↗
  2. Phase 3 registrational program initiated (adjunctive MDD; five studies, three pivotal).↗
  3. Licensing dealNeurocrine in-licenses osavampator (NBI-1065845 / TAK-653) from Takeda↗
Phase 2Apr 2024
  1. Positive Phase 2 SAVITRI topline; primary + secondary endpoints met at 1 mg.↗

Osavampator (NBI-1065845) for Major depressive disorder#

Phase 3RecruitingMajor depressive disorder indication →

Adjunctive treatment for adults with MDD and inadequate response to ≥1 antidepressant. Phase 2 SAVITRI (NCT05203341) met its primary endpoint (1 mg). Phase 3 registrational program (five studies, three pivotal) initiated January 2025.

Clinical trials#

NCT06911112NBI-1065845-MDD3025Phase 3Recruitingn=200

NBI-1065845 as Adjunctive Treatment in Major Depressive Disorder (Phase 3)

Started Mar 2025· Primary completion Jul 2027· 10 sites across 1 country

United States

NCT06786624Phase 3Recruitingn=200

NBI-1065845 as Adjunctive Treatment in Major Depressive Disorder (Phase 3)

Started Jan 2025· Primary completion Jul 2027· 18 sites across 1 country

United States

NCT05203341SAVITRIPhase 2Completedn=183

Efficacy and Safety of NBI-1065845 in Adults With Major Depressive Disorder (SAVITRI)

Started Feb 2022· Primary completion Jan 2024· 41 sites across 6 countries

United StatesBulgariaCzechiaSweden

metprimaryMADRS change at Day 28 (1 mg vs placebo) — -4.3 points (0.0159)

1 mg dose met the primary endpoint; effect deepened to -7.5 at Day 56 (p=0.0016).

Conference coverage#

NBI-1065845 appears in 1 CNS Pulse conference abstract:

Sources#

  1. Agonist-dependent activation of AMPA-R by TAK-653 — Neuropsychopharmacology (PMC)
  2. clinicaltrials.gov — ClinicalTrials.gov
  3. clinicaltrials.gov — ClinicalTrials.gov
  4. Neurocrine Announces Amendment to Strategic Collaboration with Takeda for Osavampator — Neurocrine Biosciences (PR Newswire)
  5. Neurocrine Biosciences Reports Positive Phase 2 Data for NBI-1065845 in Adults with Major Depressive Disorder — Neurocrine Biosciences
  6. Phase 3 registrational program for osavampator — Neurocrine / PR Newswire
  7. Positive Phase 2 data for NBI-1065845 in MDD — Neurocrine / PR Newswire
  8. SAVITRI (NCT05203341) — ClinicalTrials.gov