Neurocrine’s Takeda-Partnered Drug Candidate Aces Phase II Depression Study

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Pictured: Man sitting on the floor with his head in his hands/iStock, gorodenkoff

Neurocrine Biosciences on Tuesday released topline data from the Phase II SAVITRI study showing that its investigational drug NBI-1065845, being developed in partnership with Takeda Pharmaceuticals, can significantly lower depression severity in adults with major depressive disorder.

Results from SAVITRI—which enrolled 183 patients who had previously shown inadequate responses to antidepressants—demonstrated that an undisclosed once-daily oral dose of NBI-1065845 could reduce the Montgomery Åsberg Depression Rating Scale (MADRS) total score by 4.3 points versus placebo at 28 days. This effect was statistically significant, with a p-value of 0.0159, according Neurocrine.

In major depressive disorder (MDD), the MADRS is used to quantify the severity of depressive episodes. At day 58, NBI-1065845’s effect improved resulting in a 7.5-point drop in the total MADRS score relative to placebo.

A second undisclosed dose also “demonstrated a trend toward improvement over placebo,” though these effects failed to cross the threshold for statistical significance both at day 28 and 56.

In terms of safety, NBI-1065845 was also generally well-tolerated. Its most common side effect was headache and its overall adverse event profile was comparable to that of placebo. SAVITRI recorded no deaths or serious adverse events, while its dropout rates were low.

Neurocrine CMO Eiry Roberts called these topline findings “very encouraging” in a statement. “Many millions of people living with major depressive disorder do not fully benefit from currently available treatments and experience persistent debilitating symptoms,” Roberts added, noting that “NBI-1065845 has the potential to be a first-in-class treatment” for these symptoms.

Originally developed by Takeda, NBI-1065845 is an investigational positive allosteric modulator of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor. In June 2020, Neurocrine paid $120 million upfront and pledged up to $495 in development milestones for the license to develop and commercialize seven psychiatry programs, three of which are clinical-stage including NBI-1065845.

Under the terms of the agreement, Neurocrine would be responsible for developing and commercializing all candidates covered by the deal. Takeda will also be entitled to up to $1.4 billion in commercial milestones, plus up to double-digit royalties on net sales.

In November 2023, Neurocrine discontinued the development of one of the Takeda programs—dubbed NBI-1065846—after it failed to demonstrate a significant improvement in anhedonia in the Phase II TERPSIS study in patients with MDD.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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