Neurocrine hit with one-two punch as Takeda and Xenon pacts deliver midphase flops

Neurocrine Biosciences delivered a double dose of bad news after markets closed Thursday, revealing the failures of phase 2 proof-of-concept trials of an epilepsy candidate and a Takeda-partnered psychiatry program.

The San Diego-based biotech picked up the psychiatry candidate, NBI-1065846, from Takeda in 2020 as part of a multi-asset deal worth $120 million upfront. Neurocrine began a phase 2 clinical trial of the molecule the following year, enrolling patients with anhedonia—the inability to feel pleasure—in major depressive disorder on the strength of evidence that agonism of GPR139 may improve outcomes.

That hypothesis crumbled under the glare of a midphase trial. The study missed its primary endpoint, which looked at the change in anhedonia severity on Day 57. And, while Neurocrine is yet to share data publicly, it has seen enough internally to halt development of the once-weekly oral drug candidate.

The setback still leaves Neurocrine with opportunities to deliver a return on its investment in the Takeda programs. The partners are continuing to collaborate on clinical-phase treatments for major depressive disorder and cognitive impairment associated with schizophrenia.

Neurocrine is still digging into the implications of the failure of its other candidate, NBI-921352. The asset, a NaV 1.6 inhibitor that Neurocrine licensed from Xenon Pharmaceuticals for $50 million upfront, failed to meaningfully reduce seizure frequency in a phase 2 dose finding study in adults with focal onset seizures (FOS).

The failure prompted Neurocrine to halt plans to develop the molecule in FOS. A study of the candidate in SCN8A-developmental epileptic encephalopathy is continuing while Neurocrine checks whether the FOS data have any implications for the ongoing trial. The SCN8A study is scheduled to finish early next year. Work on a preclinical Nav1.2/1.6 inhibitor is continuing under the alliance between Neurocrine and Xenon. 

Shares in Neurocrine fell 6% to $105 in after-hours trading in the aftermath of the news. The biotech’s prospects are more closely tied to the commercial performance of the blockbuster Ingrezza and work to bring crinecerfont to market than either of the failed midphase programs.

Mizuho Securities analyst Uy Ear called the results disappointing, but the firm had low confidence going into the readout and had forecasted modest sales for the assets. While NBI-1065846 still has potential in SCN8A, Ear noted that the ultra-rare disease has a patient population of about 800 worldwide.