Top-line data from Relmada Therapeutics Inc.'s phase II study of REL-1017 (dextromethadone) in patients with treatment-resistant depression caused the stock to more than double Tuesday, a great day on the market.
Yes, agreed CEO Sergio Traversa, but he quickly brushed that aside to enthusiastically praise what he saw as compelling results. "I don't remember seeing data this clean," he told BioWorld.
Relmada's stock (NASDAQ:RLMD) shot up 135% on Tuesday to close at $26.20 a share.
A large component of Traversa's CV is devoted to treating forms of depression. He's been in management for more than 25 years in investment and strategic advisory roles. As a member of Eli Lilly and Co.'s CNS team, he was involved with Prozac's launch in January 1988. When Zyprexa (olanzapine) and Cymbalta (duloxetine) were developed to treat schizophrenia, Traversa was in the room where it happened.
The REL-1017 phase II evaluated the safety, tolerability and efficacy of two doses of the drug, 25 mg once daily and 50 mg once daily, as an adjunctive treatment for adult patients with major depressive disorder who did not respond to one to three courses of antidepressant treatment in their current episode. Top-line data for the double-blind, placebo-controlled trial showed REL-1017 had a rapid onset and sustained antidepressant efficacy with statistically significant differences compared to placebo on all efficacy measures.
Sixty-two patients, averaging about 49 years of age, were randomized in three arms of the study. Efficacy measures included the Montgomery-Asberg Depression Rating Scale (MADRS); the Clinical Global Impression-Severity scale; the Clinical Global Impression-Improvement scale; and the Symptoms of Depression Questionnaire. The average Hamilton Depression Rating Scale for each was 25.3 and the average MADRS score was 34, marking extreme depression.
Both dosage groups showed statistically significant improvement compared to patients taking placebo. Improvement showed up on the MADRS scale on day four in both dosage group and stayed there through days seven and 14, a full week after discontinuing the treatment. The day two "p" value for the 25-mg vs. placebo group was 0.43, and at 0.0087 on day four, at 0.0122 on day seven and 0.0103 on day 14. In the 50-mg dosage group vs. placebo, the day two "p" value was 0.9092, and at 0.0096 on day four, at 0.0308 on day seven and 0.0039 on day 14.
The large effect sizes, a measure of the difference between the two groups, ranged from 0.7 to 1. Much the same result emerged from the CGI-S and CGI-I scales.
The safety and tolerability of REL-1017's profile was confirmed as patients experienced mild and moderate adverse events but no serious adverse events. There were no significant differences between the placebo and treatment groups.
The N-methyl-D-aspartate receptor antagonist, used on the same binding site as ketamine, was fast tracked for the adjunctive treatment of major depressive disorder in 2017. Traversa noted REL-1017's similarity to ketamine but without "the baggage of side effects." Those side effects can include nausea, lack of appetite, dizziness, blurred vision and insomnia.
"With any traditional antidepression medicine, it takes three , four, six weeks before you see a response," Traversa said. "With this class of drug, on day four, boom, there is a connection between it and lifting depression."
With more than a thousand pages of data to sift through, Traversa plans to speak to the FDA as soon as he can but he doesn't want to be in a hurry. Getting in front of the FDA without knowing everything about the results is the last place he said he wants to be. A meeting could possibly happen before the year ends but he wouldn't be surprised if the two don't sit down until next year.
From what he's seen of the data, Traversa added, the results are strong enough for two traditional phase III studies. Further clinical study also means raising more money.
"If you have good science and good people, capital will come," he said. "We've never had a problem with that. It's mostly infrastructure that's an issue. We don't have the infrastructure yet to do five different indications at the same time. I tend to be conservative by nature. I tend to be realistic. I've seen a lot. I've seen companies that dream of doing things, then realize too late that it's not possible."