Neurocrine Biosciences’ osavampator has met its primary and secondary efficacy endpoints during a mid-stage trial in major depressive disorder (MDD).
During the Phase II SAVITRI study (NCT05203341), osavampator, otherwise known as NBI-1065845, met its primary endpoint – with a dose of 1mg offering a statistically significant 4.3 drop in placebo-adjusted depression scores from baseline after 28 days.
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Adjuvant osavampator’s impact on depression scores also deepened after prolonged usage, with patients receiving a 1mg dose experiencing a 7.5 point reduction on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 56 days. MADRS is a widely used measure of symptom severity in MDD clinical trials.
Meanwhile, a 1mg dose of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric modulator also triggered MDD remission significantly more than placebo, with 48.7% of patients receiving osavampator reaching this state by 56 days. In this study, remission was characterised by a MADRS score of 10 or lower.
However, there was no significant change to MADRS scores in patients allocated to the 3mg dosing arm, with individuals in this subgroup experiencing a mean 3.6 point reduction from baseline after 56 days of treatment. It was a similar case for remission rates, with 31.7% of patients experiencing a reduction in MADRS score compared with 22.8% in the placebo group.
Osavampator also overcame the common safety issues associated with this drug class, with no severe treatment-emergent adverse events (TEAEs) such as seizures linked to its administration. During the Phase II trial, the TEAEs were generally consistent with the placebo group, with most reported events being headache and nasal passage inflammation.
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By GlobalDataThe positive results of the SAVITRI trial will be welcome news for Neurocrine, which initiated a Phase III registrational programme for osavampator in January 2025. This initiative includes five studies, of which three are pivotal, currently active and enrolling patients.
Osavampator analyst outlook bright
Following the promising results of the mid-stage trial on the AMPA receptor, Philippa Salter, managing neurology analyst at GlobalData – parent company of Clinical Trials Arena – noted that Neurocrine could be on to a winner with osavampator.
She said: “Neurocrine is targeting patients who have failed to respond to an oral antidepressant, which is a group of patients with high unmet need.
“Osavampator also has a novel mechanism of action (MOA) – differentiating it from available antidepressants.”
Due to its unique MOA, strong efficacy and favourable tolerability profile, Salter stated that osavampator could see “good uptake in the MDD market as an adjunctive therapy,” if it were to display strong efficacy results in Phase III.
She added: “Though osavampator would have to compete with atypical antipsychotics such as aripiprazole and quetiapine, which are already well established on the market, it could become an attractive option given that this drug class is often associated with a poorer side effect profile.”
William Blair research analyst Myles Minter echoed this sentiment, stating that osavampator’s safety profile is “clearly differentiated from prior orthosteric agonist approaches developed by Eli Lilly (LY 451646), Biogen (pesampator) and GSK (GSK 729327)”.
He noted: “We view the 0.73 effect size on MADRS for the 1mg osavampator dose at day 56 as impressive, given that the majority of currently approved antidepressants are in the 0.2-0.3 range.”
He also highlighted that this figure is numerically greater than Johnson & Johnson’s Caplyta (lumateperone), which showed effect sizes between 0.56 and 0.62 in the adjunctive setting in MDD, and is currently under FDA review for the indication.
“Though drug development in MDD remains high-risk, high-reward, Neurocrine has three ongoing pivotal studies, which provide another shot on goal as only two positive studies would be required for a potential regulatory filing,” Minter concluded.
