A week after reporting a successful phase 3 trial of Sunosi (solriamfetol) in patients with attention-deficit/hyperactivity disorder (ADHD), Axsome Therapeutics has unveiled mixed results for the same compound in a study in patients with major depressive disorder (MDD).
Investigating Sunosi as a treatment for MDD patients with and without excessive daytime sleepiness (EDS), a phase 3, proof-of-concept study did not meet its primary endpoint, Axsome said Tuesday. But, while the trial failed to succeed in its overall patient population, it did show some improvements in those with EDS.
The study was not set up to demonstrate statistical significance in the prespecified subgroups. But, based on the results, Axsome said it plans to kick off a phase 3 trial in MDD patients with EDS later this year.
“The promising results with solriamfetol in MDD patients with severe EDS align with its known pharmacology and support its further evaluation in this potentially new indication,” Axsome’s CEO and founder Herriot Tabuteau, M.D., said in a release.
With news of the trial failure, Axsome's share price dropped by 8%, but analysts from Mizuho Securities said investors shouldn't be concerned.
"Based on our conversations with the buy-side, we believe expectations were very low on this data event (and we believe most didn't have MDD for solriamfetol in their estimates)," Mizuho wrote. "As a result, we believe any direct stock weakness on today's negative outcome in MDD should be relatively limited."
In the six-week proof-of-concept study, which included 51 participants with severe EDS, daily treatment with a 300-mg dose of Sunosi resulted in “clinically meaningful and numerically greater improvements compared to placebo” in multiple efficacy measures, including the Montgomery-Åsberg Depression Rating Scale, Axsome said.
Among the 291 patients in the study without severe EDS, there was no meaningful difference as compared to placebo on the study endpoints, Axsome added.
Even though the study had significantly more patients without EDS, the symptom is prevalent in roughly half of those with MDD, according to Axsome. There are no treatments approved specifically for those with MDD and EDS.
Axsome acquired Sunosi three years ago from Jazz Pharmaceuticals for $53 million upfront after the Ireland drugmaker scored a 2019 FDA approval for the dopamine and norepinephrine reuptake inhibitor to treat patients with EDS associated with narcolepsy or obstructive sleep apnea.
In addition to ADHD and MDD, Axsome also is investigating Sunosi as a treatment for binge eating disorder and excessive sleepiness associated with shift work disorder.
Given its novel mechanism of action and strong efficacy data, Leerink projected upon its approval potential peak Sunosi sales of $500 million. But Sunosi never approached that trajectory under Jazz, which reported the drug's sales at $58 million in 2021. Sunosi has shown more promise under the wing of Axsome as sales last year reached $94 million. Mizuhonow is tabbing Sunosi's peak sales potential at between $1 billion and $1.5 billion.
Flunking the trial was a rare defeat for the 12-year-old company, which has been on a roll, securing an FDA nod two months ago for migraine treatment Symbravo, which has been tabbed as a potential blockbuster.
Axsome’s first approval came in 2022 for MDD treatment Auvelity, which racked up sales of $291 million last year.