Neurocrine Biosciences has been hit with a pair of mid-stage failures for its partnered candidates in major depressive disorder (MDD) and focal onset seizures (FOS), leading the biotech to wind down the MDD program altogether and home in on a much smaller market opportunity for the seizure candidate.
The placebo-controlled Phase II TERPSIS trial was evaluating Takeda-partnered drug NBI-1065846 in 93 MDD patients with anhedonia, which is the inability to feel pleasure. The treatment did not meet the primary endpoint of change in anhedonia severity, measured by the Dimensional Anhedonia Rating Scale score at 57 days. The company said it is discontinuing further development of the drug.
Neurocrine paid $120 million upfront for the rights to three of Takeda’s clinical-stage compounds for psychiatric diseases — including NBI-1065846 — back in 2020. Phase II development of the remaining two compounds in major depressive disorder and cognitive impairment associated with schizophrenia is ongoing, Neurocrine said.
The other placebo-controlled Phase II trial tested a Xenon Pharmaceuticals-partnered NaV1.6 sodium channel inhibitor, dubbed NBI-921352, in patients with FOS. The treatment failed to demonstrate a meaningful decrease in seizure reduction. The company’s management had said they wanted to double the reduction in seizures with treatment compared to placebo, Mizuho Securities analysts highlighted.
NBI-921352 was among several preclinical-stage compounds in which Neurocrine paid $50 million upfront to Xenon in 2021. The company said it is not planning further development of the drug in FOS. However, the drug remains in a Phase II trial for SCN8A developmental and epileptic encephalopathy (SCN8A-DEE) syndrome with a readout expected in 2024.
“Targeted sodium channel inhibition … could have a better chance of showing a clear signal in SCN8A-DEE,” because the disease is caused by a gain-of-function mutation of the NaV1.6 sodium channel, the Mizuho analysts said. However, SCN8A-DEE is an orphan indication with just 800 patients worldwide compared with the larger FOS market.
The NBI-1065846 trial failure is not the first to come out of the Neurocrine-Takeda partnership. In 2021, the duo’s schizophrenia drug candidate, luvadaxistat, failed to meet the primary endpoint of reducing schizophrenia symptoms in a Phase II trial. But it did meet a secondary endpoint related to cognitive performance and is now under development for this niche.
The Takeda deal is worth a potential $2 billion in biobucks and was inked as part of the pharma major’s restructuring following the buyout of Shire.
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