Takeda's licensed Neurocrine biologic drug fails mid-stage test for depression
An experimental depression drug added to Neurocrine Biosciences' pipeline as part of Takeda Pharmaceutical's broader portfolio failed to meet a key goal in a mid-stage clinical trial. The biotech hasn't given up on the asset yet, but even if it does, it has another depression drug from the Takeda deal that works differently and is in further clinical development.
What failed in this trial was an oral small molecule code-named NBI-1070770. Neurocrine said late Monday that the drug did not meet its primary goal of showing changes on a widely used rating scale that assesses the severity of depressive symptoms. While the San Diego-based biotech didn't reveal specific details, it did say the drug was well tolerated by study participants.
NBI-1070770 was developed to track NMDA receptors located throughout the central nervous system. There are already depression drugs that target this: Johnson & Johnson's Spravo and Axsome Therapeutics' Auvelity both block it. Neurocrine's drug is a negative allosteric modulator, meaning it binds not to the primary site but to the secondary site of its target. The target is the NR2B subunit of NMDA. One advantage of attacking subunits with drugs is fewer side effects.
Phase 2 testing of NBI-1070770 enrolled 73 adults diagnosed with major depressive disorder who had an inadequate response to at least one antidepressant. Participants were randomly assigned to receive one of three doses of study drug or placebo. The primary objective was to assess changes in depression severity from baseline to day 5. The secondary objective was to measure change from baseline to day 49.
Leerink Partners analyst Marc Goodman wrote in a note to investors that expectations for Neurocrine's trial results are low, given the failure of previous drugs targeting the NR2B subunit of NMDA. He cited the 2019 Phase 3 failure of rapastinel, a drug being developed by Allergan (now part of AbbVie after its 2020 acquisition) to treat major depressive disorder, as an example.
In 2020, Neurocrine paid Takeda $120 million up front for development and commercialization rights to NBI-1070770, as well as three additional clinical-stage psychiatry drug candidates and three non-clinical assets. One of the clinical-stage drugs, luvadaxistat, failed last year to meet the primary goal of a Phase 2 trial to treat the cognitive impairment associated with schizophrenia. Neurocrine subsequently terminated the license for the drug. Neurocrine Pipeline still lists two late-stage assets in the Takeda deal: NBI-1117568 for schizophrenia and osavampator for major depressive disorder.
The original deal called for Neurocrine and Takeda to equally share profits or losses from osavampator. Last January, the companies changed their agreement to a royalty-based license, granting Neurocrine exclusive rights to develop and commercialize the drug in all indications worldwide (excluding Japan). Osavampator is a positive allosteric modulator of a target called AMPA and is currently undergoing Phase 3 testing. In Phase 2 results reported in September, the once-daily oral medication showed statistically significant and clinically meaningful improvements in depression severity measured at days 28 and 56.
As for NBI-1070770, Neurocrine describes its Phase 2 testing as a signal discovery study. Despite the failure of the trial, company executives say there may be more to learn.
“While we are disappointed that NBI-1070770 did not meet the primary endpoint, there are aspects of the data that warrant further exploration,” Chief Medical Officer Sanjay Keswani said in a prepared statement. “Our team will continue to analyze these results so that we can determine appropriate next steps.”
Photo: Jolygon, Getty Images
