Supernus Pharmaceutical’s stock declined following the release of disappointing Phase IIb trial results for SPN-820, an investigational treatment for adults with treatment-resistant depression (TRD).
The company announced on 18 February that the trial did not meet its primary endpoint measured by a depression rating scale, with no statistically significant difference observed between the treatment and placebo groups. Supernus’ stock is down 17% from the close on 18 February to open on 19 February.
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The Phase IIb study (NCT05066672) enrolled 250 adult patients with TRD, who were randomised to receive either two or four 400mg doses of SPN-820 daily. After four weeks, patients receiving SPN-820 showed a 12.3-point reduction on the Montgomery-Åsberg Depression Rating Scale (MADRS), which assesses depression severity. However, the placebo group experienced an 11.9-point reduction, meaning the difference between the groups was not statistically significant. Supernus also reported no statistically significant differences in secondary endpoints.
SPN-820, a mechanistic target of rapamycin complex 1 (mTORC1) activator, previously demonstrated promising results in an open-label Phase IIa trial (NCT06235905) conducted in patients with major depressive disorder (MDD). In that study, the drug showed a clinically meaningful improvement of -6.1 on the Hamilton Depression Rating Scale-6 items (HAM-D6) at two hours, improving to -9.6 by day ten. Suicidal ideation decreased by 80%, from 12.5% at baseline to 2.6% on day ten.
In an October 2024 conference call, Supernus’s CMO Jonathan Rubin said the company would decide which indication to pursue further out of MDD or TRD based on the yet-to-be-unveiled latest Phase IIb data for the latter indication.
Supernus licensed SPN-820 from Navitor Pharmaceuticals in 2020. The agreement included a $10m upfront payment and a $15m investment, with total potential payments exceeding $400m if all milestones are met.
“We are disappointed that the trial did not meet its primary endpoint in this patient population,” said Supernus CEO Jack Khattar, who added that the company will continue to analyse the data and will discuss the future of the programme with Navitor.
SPN-820 is not the only candidate in Supernus’s pipeline, should the company decide not to press ahead with its further development. The developer also has SPN-817, a reversible acetylcholinesterase inhibitor being developed for severe epilepsy. The candidate demonstrated positive results in an open-label Phase IIa trial (NCT05518578) and is currently being investigated in a larger placebo-controlled Phase II trial (NCT06798896).
The standard of care for major depressive disorder (MDD) typically involves selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) as first-line treatments, often in combination with psychotherapy. However, these therapies can take weeks to take effect, and many patients do not respond adequately, leading to a need for innovative alternatives.
Last month, Johnson & Johnson’s (J&J) nasal spray Spravato (esketamine) received a label expansion as a monotherapy treatment for MDD in adults who do not respond to two oral antidepressants. The US Food and Drug Administration’s (FDA) decision made Spravato the first-ever standalone treatment for adults with treatment-resistant depression.
