Supernus reports less than super data for depression drug

Supernus Pharma has suffered a blow to its R&D pipeline after a candidate for treatment-resistant depression failed a phase 2b trial, sending its share into a tailspin.

The stock was down nearly 20% in pre-market trading after the announcement, which revealed that SPN-820 – which the company has said could be a first-in-class oral antidepressant therapy – was unable to achieve a statistically significant improvement on the primary endpoint, the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, compared to placebo at week four.

There was also no significant effect on secondary endpoints in the 250-patient study, such as Clinical Global Impression-Severity (CGI-s) scores, according to the Rockville, Maryland-based company.

SPN-820 is designed to enhance synaptic function in the brain by activating the mechanistic target of the rapamycin complex 1 (mTORC1) pathway, which has been referred to as a "gatekeeper of cellular metabolism and renewal" that is often suppressed in people with depression.

Supernus entered into a collaboration with Navitor Pharmaceuticals in 2020 to collaborate on the development of the drug, which is also known as NV-5138, paying an upfront fee of $25 million with a total deal value of up to $475 million.

"We are disappointed that the trial did not meet its primary endpoint in this patient population," said Jack Khattar, president and chief executive of Supernus. "We will continue to analyse these data and discuss the future of the program with our development partner," he added.

The readout comes just a few months after the two partners revealed data from a 40-patient phase 2a trial in major depressive disorder (MDD), which they said showed a "rapid and substantial" effect on symptoms just two hours after dosing.

The benefit was seen without dissociation – a feeling of emotional detachment – and other side effects sometimes reported with current antidepressants.

In particular, the speed-of-onset data drew a lot of attention as current drugs used to treat MDD, such as selective serotonin reuptake inhibitor (SSRI) drugs like fluoxetine and sertraline, can take weeks to show an effect.

Faster-acting drugs have long been sought to protect people with severe depression who may be at risk of self-harm or suicide, and Supernus and Navitor's study found that suicidal ideation decreased by 80% over 10 days.