The company announced the successful completion of a meeting with the U.S. Food and Drug Administration (FDA) following the phase 2 study of its lead candidate drug navacaprant for the treatment of major depressive disorder (MDD). The company expects to launch its first phase 3 trial of the candidate drug later this year.
MDD is a chronic condition that often comes with symptoms including low mood and anhedonia. Only a minority of MDD patients respond to first-line antidepressants, which can cause side effects including weight gain and insomnia. Navacaprant is an oral small molecule drug designed to tackle the condition by blocking proteins called kappa opioid receptors (KORs) and modulating the action of dopamine in the brain.
The phase 2 trial of once-daily navacaprant was originally launched by BlackThorn Therapeutics in patients with mild-to-moderate MDD. Neumora acquired BlackThorn when it was launched in 2021 and later added patients with moderate-to-severe MDD to the trial plan.
Among the 100 patients in the moderate-to-severe MDD population, navacaprant significantly improved symptoms of depression over eight weeks, measured using the 17-item Hamilton Rating Scale for Depression (HAMD-17). The drug also significantly improved feelings of anhedonia, which was measured using a metric known as the Snaith-Hamilton Pleasure Scale (SHAPS).
Among the total population of 171 patients, which also included those with mild-moderate MDD, navacaprant significantly reduced depression symptoms after 4 weeks but failed to meet BlackThorn’s original primary endpoint of beating the placebo after 8 weeks. Nonetheless, the drug did significantly improve anhedonia at both time points.
Neumora also reported promising a safety signal from the candidate drug, with the majority of the emergent adverse events being mild to moderate and none classed as severe.
“Major depressive disorder remains one of the most prevalent psychiatric disorders and is associated with high rates of morbidity and functional impairment,” stated Roger McIntyre, professor of psychiatry and pharmacology, University of Toronto, Canada, in Neumora’s public release.
“Anhedonia, the inability to experience pleasure or joy, impacts a majority of MDD patients and is a complex and challenging symptom that often remains untreated by current antidepressants. A growing body of research suggests that anhedonia is also a core risk factor for suicidal ideation, demonstrating the importance of studying and identifying new treatments that could improve care for impacted patients.”
Going forward, Neumora plans to launch its first phase 3 trial of navacaprant in adult patients with moderate-to-severe MDD in the U.S. in the third quarter of 2023. A second phase 3 study is expected in the fourth quarter of this year, and a third is planned in early 2024. If it proceeds to plan, the company expects to apply for FDA approval in 2025.
Neumora is developing navacaprant for the treatment of other neuropsychiatric disorders in phase 2. The firm is also developing a pipeline of other candidates for the treatment of neuropsychiatric disorders and neurodegenerative diseases such as agitation in Alzheimer’s disease.
The KOR system is a target for many other companies seeking to treat MDD and other mental health disorders. Alkermes’ drug candidate ALKS 5461 was shot down for the treatment of MDD by the FDA in 2019. One current example is Johnson & Johnson, which is developing a candidate called aticaprant in a phase 3 trial for the treatment of MDD and anhedo