Poster
34
(#34) Osavampator: A selective positive allosteric modulator of the AMPA receptor (AMPA-PAM) in Development for the Treatment of Major Depressive Disorder
Psych Congress 2025
Abstract: Major depressive disorder (MDD) remains a leading cause of disability worldwide. Approximately two-thirds of individuals with MDD do not remit in response to first-line therapies. Limited efficacy and poor tolerability contribute to low treatment adherence. Consequently, novel strategies targeting molecular pathways that enhance synaptic plasticity and exert antidepressant effects are needed.
Osavampator (NBI-1065845/TAK-653) targets the glutamate system and is a selective positive allosteric modulator of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPA-PAM). It is in development as a treatment for MDD. In preclinical studies, osavampator increased brain-derived neurotrophic factor levels and activated mammalian target of rapamycin signaling. Both mechanisms are associated with enhanced synaptic plasticity and antidepressant-like effects.
In healthy volunteers, osavampator was generally well tolerated. Single doses up to 18 mg and multiple doses up to 9 mg daily for 13 days were not associated with serious adverse events, deaths, or adverse events of special interest, including seizures. In individuals with MDD, an oral loading dose of 6 mg followed by 3 mg daily for 14 days was also well tolerated.
In the phase 2 SAVITRI study (NCT05203341), once-daily oral administration of osavampator 1 mg and 3 mg resulted in improvements in Montgomery-Åsberg Depression Rating Scale total scores at both Day 28 and Day 56 versus baseline, with only the 1 mg dose achieving statistical significance. Osavampator was well tolerated, with no clinically significant safety concerns.
By modulating AMPA receptor activity, osavampator may help address limitations of current antidepressant therapies. Ongoing clinical trials will further evaluate its efficacy and safety profile.
Short Description: Osavampator (NBI-1065845/TAK-653) is a selective positive allosteric modulator of the AMPA receptor (AMPA-PAM) in development for MDD. In preclinical studies, osavampator increased brain-derived neurotrophic factor and activated pathways associated with synaptic plasticity and antidepressant-like effects. Compared with placebo, once-daily oral administration of 1 mg and 3 mg resulted in improvements in Montgomery-Åsberg Depression Rating Scale total scores at Day 28 and Day 56 versus baseline. Osavampator was well tolerated, with no clinically significant safety concerns.
Name of Sponsoring Organization(s): Neurocrine Biosciences Inc
Osavampator (NBI-1065845/TAK-653) targets the glutamate system and is a selective positive allosteric modulator of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPA-PAM). It is in development as a treatment for MDD. In preclinical studies, osavampator increased brain-derived neurotrophic factor levels and activated mammalian target of rapamycin signaling. Both mechanisms are associated with enhanced synaptic plasticity and antidepressant-like effects.
In healthy volunteers, osavampator was generally well tolerated. Single doses up to 18 mg and multiple doses up to 9 mg daily for 13 days were not associated with serious adverse events, deaths, or adverse events of special interest, including seizures. In individuals with MDD, an oral loading dose of 6 mg followed by 3 mg daily for 14 days was also well tolerated.
In the phase 2 SAVITRI study (NCT05203341), once-daily oral administration of osavampator 1 mg and 3 mg resulted in improvements in Montgomery-Åsberg Depression Rating Scale total scores at both Day 28 and Day 56 versus baseline, with only the 1 mg dose achieving statistical significance. Osavampator was well tolerated, with no clinically significant safety concerns.
By modulating AMPA receptor activity, osavampator may help address limitations of current antidepressant therapies. Ongoing clinical trials will further evaluate its efficacy and safety profile.
Short Description: Osavampator (NBI-1065845/TAK-653) is a selective positive allosteric modulator of the AMPA receptor (AMPA-PAM) in development for MDD. In preclinical studies, osavampator increased brain-derived neurotrophic factor and activated pathways associated with synaptic plasticity and antidepressant-like effects. Compared with placebo, once-daily oral administration of 1 mg and 3 mg resulted in improvements in Montgomery-Åsberg Depression Rating Scale total scores at Day 28 and Day 56 versus baseline. Osavampator was well tolerated, with no clinically significant safety concerns.
Name of Sponsoring Organization(s): Neurocrine Biosciences Inc
