Phase 3 Study Initiated: Osavampator as Adjunctive Therapy for Major Depressive Disorder

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Neurocrine Biosciences just announced the initiation of a phase 3 registrational study to evaluate the efficacy, safety, and tolerability of osavampator, an investigational drug under development as an adjunctive treatment to antidepressants for major depressive disorder (MDD). Investigators will enroll adults with a primary diagnosis of MDD who have inadequate response to current, oral antidepressant treatment.¹

"Major depressive disorder is a condition that has a profound effect on patients and their families and is associated with significant morbidity and mortality," said Maurizio Fava, MD, chair of Mass General Brigham Academic Medical Centers Department of Psychiatry. "The great majority of patients suffering from major depressive disorder do not achieve a sustained remission of their condition and the options for next step strategies to help them are quite limited. This trial is happening at a time when it is clear that, as a field, we need to develop new augmentation strategies to enhance the efficacy of standard antidepressants."

Key inclusion criteria for this phase 3 study include:

1. A primary diagnosis of recurrent MDD (moderate or severe) or persistent depressive disorder.
2. Inadequate response to oral antidepressant treatments in the current episode of depression.
3. Taking oral antidepressants for at least 8 weeks and is willing to continue the same oral antidepressants at the same dose and frequency of administration throughout participation in the study.
4. Total Hamilton Depression Rating Scale-17 Item (HAM-D17) score ≥22 at screening and at study baseline (day 1).
5. Willing and able to comply with all study procedures and restrictions.

Key exclusion criteria include:

• A current or prior psychiatric disorder diagnosis other than MDD in the last year that was the primary focus of their treatment.
• Considered by the investigators to be at imminent risk of suicide or injury to self or others.
• Depressive symptoms have previously demonstrated nonresponse to electroconvulsive therapy in the current major depressive episode.

Osavampator, formerly NBI-1065845, is a potential first-in-class, investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid positive allosteric modulator. Positive topline data for the phase 2 SAVITRI study of osavampator in adult participants with MDD were announced in April 2024: osavampator met its primary and secondary endpoints, and was generally well tolerated. Osavampator produced a statistically significant change from baseline in Montgomery Åsberg Depression Rating Scale (MADRS) total score at both day 28 (primary) and day 56 (secondary). The least squares mean differences from baseline in MADRS total score for osavampator were: (1) One of the doses demonstrated an improvement over placebo of -4.3 (P = 0.0159) and -7.5 (P = 0.0016) at day 28 and day 56, respectively, and (2) The other dose also demonstrated a trend toward improvement over placebo of -3.0 (P = 0.0873) and -3.6 (P = 0.1082) at day 28 and day 56, respectively.

"[Osavampator] has the potential to be a first-in-class treatment to alleviate many of these symptoms of MDD. The phase 2 data from the SAVITRI study are very encouraging, and we look forward to meeting with the FDA to discuss a path into phase 3 studies,” said Eiry W. Roberts, MD, chief medical officer at Neurocrine Biosciences.²

The most common adverse event was headache, and the adverse event profile for both doses of osavampator were comparable with placebo. There were no deaths or serious adverse events and discontinuation rates were low throughout the study.²

"Osavampator has the potential to become a first-in-class treatment for MDD, a disorder that impacts more than 21 million people in the United States," said Roberts. "More than a third of those MDD sufferers endure debilitating symptoms that current treatment options cannot fully resolve."¹

Neurocrine received an exclusive license to osavampator from Takeda Pharmaceutical Company Limited for all indications in all territories worldwide except Japan.

References

1. Neurocrine Biosciences announces initiation of phase 3 registrational program for osavampator as an adjunctive therapy for the treatment of major depressive disorder in adults. News release. January 28, 2025. https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-initiation-of-phase-3-registrational-program-for-osavampator-as-an-adjunctive-therapy-for-the-treatment-of-major-depressive-disorder-in-adults-302361369.html

2. Neurocrine Biosciences reports positive phase 2 data for NBI-1065845 in adults with major depressive disorder. News release. April 23, 2024. Accessed January 28, 2024. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-reports-positive-phase-2-data-nbi-1065845