- A ketamine-based nasal spray developed by Johnson & Johnson helped to significantly reduce depressive symptoms in a Phase 3 study of patients resistant to other treatments, the drugmaker announced over the weekend.
- Success of the treatment, called esketamine, moves J&J a step closer to its goal of submitting the drug to the Food and Drug Administration, possibly sometime later this year.
- Results from a second late-stage trial in older adults, however, fell short of demonstrating a statistically significant difference between the esketamine group and the control arm. J&J expects to read out more data from three other Phase 3 studies of the drug in treatment-resistant depression later this year.
Esketamine is one of three neurological candidates J&J hopes to file over the next four years in an effort to refresh a neuroscience portfolio consisting of aging drugs like Invega (paliperidone) and Risperdal (risperidone).
The positive Phase 3 results reported May 5 at the American Psychiatric Association Annual Meeting are an important milestone for esketamine. While a narrow miss from the second study complicates the picture, J&J believes the data still supports its case for the drug.
In the first study, J&J compared esketamine plus a newly initiated oral antidepressant to placebo plus an oral antidepressant. The trial enrolled patients who did not respond to two or more available treatments. Treatment with esketamine led to a significant reduction of symptoms, reducing average scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) by four points from baseline at Day 28.
A secondary endpoint measuring the onset of the clinical response, however, did not meet statistical significance. It's worth noting that the four-point reduction is less than the decrease measured in a smaller Phase 2 study.
In the second trial J&J reported Saturday — which only included patients over 65 — the reduction in MADRS scores failed to meet statistical significance. J&J notes, though, that the 3.6 median estimated difference between the two groups is consistent with the two- to three-point difference between currently approved antidepressants and placebo.
Due to the older patient population, the second study started patients on a lower dose of esketamine.
Safety results weren't fully broken out, but J&J reported more than 10% of patients given esketamine experienced treatment-emergent adverse events like dizziness, headache, increased blood pressure and dissociation.
Ketamine is a Class III Scheduled drug that is largely used as an anesthesia. The drug can be easily abused for its psycho-active effects and the street variety is nicknamed "Special K." Given ketamine's illicit use, the safety profile of esketamine will be closely watched.
About 30% of patients with major depression don't respond to current therapies, J&J estimates — a gap that esketamine would address, if approved.
J&J is also developing esketamine for major depressive disorder with imminent risk for suicide.
Esketamine is designed to bind to a receptor called N-methyl-d-aspartate. J&J is not alone in targeting this pathway, however. Allergan is also advancing a late-stage candidate, called rapastinel, in major depressive disorder.