Alto Neuroscience is advancing a depression drug based on the dopamine agonist pramipexole, which an independent study has found to help boost feelings of pleasure in patients with mood disorders.
The dopamine agonist pramipexole could help restore the ability to feel pleasure in patients with mood disorders, bolstering the case for Alto Neuroscience’s depression drug that is based on the same active compound, according to an independent study conducted by a Swedish university.
Conducted at the Lund University in Sweden, the randomized, double-blinded and placebo-controlled PRIME-PRAXOL study enrolled more than 80 patients with major depressive disorder (MDD), bipolar depression or dysthymia, a condition characterized by persistent low mood but not enough to meet the definition of MDD.
The study looked specifically at pramipexole, a dopamine agonist that works by exerting antidepressant effects across the brain. Pramipexole is approved as Boehringer Ingelheim’s Mirapex for Parkinson’s disease and restless leg syndrome, but Alto is advancing an investigational pramipexole-based treatment called ALTO-207, which combines fixed doses of the dopamine agonist with the antiemetic ondansetron.
This combo, currently in mid-stage trials, allows higher doses at a more rapid titration by preventing side effects that would otherwise have been dose-limiting, Alto said in a news release on Monday.
Results of the independent study were published Friday in Nature Medicine and showed that pramipexole significantly improved anhedonia scores on the Snaith-Hamilton Pleasure Scale. This tool, commonly known by the shorthand SHAPS, measures how much pleasure a patient derives from common daily activities, such as watching TV, spending time with family and friends or engaging in hobbies.
The independent study also found that pramipexole had stronger anhedonia benefits in patients with MDD as compared with those who had dysthymia, Alto said on Monday, presenting the paper’s findings. Pramipexole’s improvements to anhedonia were maintained throughout six months of observation.
Alto “is looking to disrupt the [central nervous system] paradigm by leveraging precision psychiatry” to maximize the success of its trials, Jefferies told investors on Monday, referring to the company’s use of biomarkers to guide the development process. The firm expects the biotech’s stock to “move significantly higher” if any of its Phase 2b readouts next year deliver promising findings.
Alto has several of these mid-stage studies running across several indications, including MDD and bipolar depression. In April, the company launched a Phase 2b study of ALTO-207 in treatment-resistant depression (TRD).
Across these studies, however, “we are particularly keen on ALTO-207’s pivotal Phase IIb dataset” in TRD, expected to come in the back half of 2027, Jefferies said. On this front, the readout from the independent PRIME-PRAXOL study “instills confidence” in ALTO-207’s success, the analysts added.
