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Psych Congress  

Number Needed to Treat Analysis of the SAGE-217 Phase 2 Clinical Trial Results in Major Depressive Disorder


Alix Arnaud, MSc – Sage Therapeutics, Inc; Ellison Suthoff, MBA – Sage Therapeutics, Inc; Katie Stenson, MSc – Sage Therapeutics, Inc; Brian Werneburg, PhD – Sage Therapeutics, Inc; Paul Hodgkins, PhD – Sage Therapeutics, Inc; Vijayveer Bonthapally, PhD – Sage Therapeutics, Inc; Jeffrey Jonas, MD – Sage Therapeutics; Kellie Meyer, PharmD, MPH – Xcenda; Ken O'Day, PhD, MPA – Xcenda

Sage Therapeutics

Background: SAGE-217 is a novel, positive allosteric modulator of GABA(A) receptors under development in Major Depressive Disorder (MDD). This analysis quantified the number needed to treat (NNT) and number needed to harm (NNH) after administration of SAGE-217 versus placebo and antidepressants.

Methods: In the phase 2 study, patients (n=89) with MDD and a Hamilton Rating Scale for Depression (HAM-D) total score ≥22 were randomized 1:1 to receive SAGE-217 capsule 30mg or placebo for 14 days, with 4 weeks follow-up. Efficacy was evaluated by HAM-D; adverse events (AEs) were reported through Day 42. The primary endpoint demonstrated a significant improvement for patients treated with SAGE-217 versus placebo at Day 15 in HAM-D total score (p<0.001). The most common AEs (≥5%) in the SAGE-217 group were headache, nausea, dizziness, and somnolence. Clinical data for 11 antidepressant comparators were obtained from a published network meta-analysis. An indirect treatment comparison of SAGE-217 versus each comparator was conducted with the Bucher method using odds ratios and SAGE-217 clinical study values to calculate NNT and NNH.

Results: SAGE-217 demonstrated greater response and remission compared to placebo (NNT=2.6 for both). Compared to SSRIs and SNRIs, SAGE-217 showed improved treatment response (NNT=3.8 and 4.2, respectively) and remission (NNT=3.4 and 3.6), accompanied by a reduction in all-cause discontinuation (NNH = -57.7 and -28.6).

Conclusions: With a small positive NNT indicating robust benefit and a negative NNH indicating reduced harm, the results demonstrate a potential favorable benefit-risk profile of SAGE-217 versus standard of care in patients with MDD.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.

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