The therapy's currently-planned phase 3 trials for major depressive disorder, postpartum depression disorder are being converted into pivotal studies after a meeting with the FDA.
An investigatory therapy for central nervous system (CNS) disorders has updated its trial schedule to expedite US Food and Drug Administration (FDA) considerations for major depressive disorder (MDD) and postpartum depression (PPD).
SAGE-217, an oral receptor inhibitor from Sage Therapeutics, has been given an expedited development plan following a Breakthrough Therapy meeting with FDA officials that includes an additional placebo-controlled phase 3 trial in patients with MDD, as well as the designation of an ongoing placebo phase 3 trial in patients with PPD as a pivotal study.
The trials, which are both designed to evaluate the reduction of depressive symptoms in patients administered an episodic dosing regimen of SAGE-217 versus placebo, are exploring the possibility of treating patients with depression within just 2 weeks. The FDA’s feedback on the pivotal trials has provided what Sage Chief Executive Officer Jeff Jonas, MD, called a “possible groundbreaking path forward.”
Jones likened the potential expediency of SAGE-217 to that of antibiotics.
“We believe a medicine with rapid onset and robust response could be truly paradigm shifting,” Jonas said in a statement. “SAGE-217, if successfully developed and approved, may rewrite the textbook on how the tens of millions of people suffering from MDD are treated, ultimately turning depression into a disorder, not an identity.”
Breakthrough Therapy Designation for SAGE-217 as an MDD therapy candidate was granted by the FDA in February. It was based on positive results from a placebo-controlled trial of 89 adult patients with moderate to severe MDD. Patients administered the investigatory therapy reported statistically significant mean score reductions in the Hamilton Rating Scale for Depression (HAM-D), a 17-item total score, from baseline to Day 15 versus those administered placebo (P < 0.0001). They also reported statistically significant improvements in HAM-D score compared to placebo patients through Week 4, with the benefits and tolerability of SAGE-217 continued to report as numerically greater than placebo through the end of follow-up at Week 6.
Common adverse events in the treatment group included headaches, dizziness, nausea, and somnolence.
SAGE-217 is a positive allosteric modulator that has been designed for selectivity to synaptic and extrasynaptic GABAA receptors, which are part of the system of the major inhibitory signaling pathway of the brain and CNS. The system contributes significantly to regulating CNS function, leaving open consideration for SAGE-217 as a therapy for other mood and movement disorders.
The expedited pivotal trials for both MDD and PPD will occur this year. The ongoing PPD trial — a multi-center, double-blind, randomized study evaluating 140 patients administered either 30 mg SAGE-217 or placebo — will resume as a supportive study for US market consideration for the indication. The additional phase 3 study testing MDD will begin in the second half of 2018, and will test 20 mg, 30 mg, or placebo therapy in 450 patients with MDD for 2 weeks of treatments and 4 weeks of additional follow-up.
The Breakthrough Therapy meeting also resulted in the FDA backing a long-term, open-label study program that will acquire additional data on potential major depressive episode treatment in approximately 400 patients following for at least 6 months after initial therapy.
Top-line data from the now-pivotal phase 3 trial of patients with PPD are expected to be announced in Q4 of this year, according to Sage. From there, the potential novel dosing regimen in patients with depression may be better evidenced.