HMNC Brain Health and Develco Pharma are forging ahead with development of oral prolonged-release ketamine after seeing a “positive trend” in treatment-resistant depression, with a midphase study slated to start in the second quarter.
The trend was detected in a phase 2 proof-of-concept study that looked at the effect of the formulation, KET01, on a depression rating scale. At the highest dose, KET01 improved on the placebo score by 4.99 units on Day 15. The difference amounted to a p-value of 0.1499 but, seeing a “positive trend in efficacy for the highest tested dose,” the researchers plan to advance into a larger study.
Enrollment in the proof-of-concept study was stopped at 27, well short of the target of 99. HMNC and Develco, which formed a joint venture, Ketabon, to advance the candidate, attributed the failure to reach the enrollment target to the pandemic and “very stringent criteria for definition of treatment resistant depression.”
The larger, multinational phase 2 clinical trial will give HMNC and Develco the chance to find out whether KET01 can improve outcomes in hard-to-treat patients. Initial results are expected around the middle of next year.
For now, the clinical evidence for the efficacy of KET01 is limited to trends seen in the small phase 2 trial. As well as sharing the primary endpoint data, the partners posted a look at the depression score results after seven days. At that time, the difference between the two arms was 5.67, giving a p-value of 0.1062 and informing the partners’ claim that KET01 has a rapid onset of action.
A nasal spray formulation of ketamine, Johnson & Johnson’s Spravato, is already approved for use in adults with treatment-resistant depression. However, HMNC and Develco think their prolonged-release formulation can minimize dissociative side effects and, in doing so, improve the risk profile and patient convenience.