The company is working to break into the broader depression market with SAGE-217. The company discussed its pipeline at its “FutureCast.”
In March, SAGE Therapeutics received approval from the U.S. Food and Drug Administration (FDA) for Zulresso (brexanalone) to treat postpartum depression (PPD). Although an important approval that drove the company’s market value to almost $9 billion, PPD is a relatively small market. Now the company is working to break into the broader depression market with SAGE-217. The company discussed its pipeline at its “FutureCast.”
“Our goal at Sage has always been to step into the void in CNS drug development through an innovative approach we believe to be unique,” stated Jeff Jonas, Sage’s chief executive officer. “By thinking differently about brain disorders, we’ve built a pipeline with the potential to deliver a broad range of new medicines across multiple indications. The clinical findings presented today are a result of our differentiated approach to discovery and translation. While these are still early data, we believe these data not only meaningfully expand our pipeline opportunities, but more importantly, represents the potential benefits our medicines may provide for patients if we’re successful in our development efforts.”
SAGE-217 is the company’s next-generation positive allosteric modulator (PAM) of GABAA receptors. It is in a Phase III trial for major depressive disorder (MDD), PPD, and comorbid MDD and insomnia. It is also being studied for bipolar depression and additional affective disorders, including treatment-resistant depression (TRD) and generalized anxiety disorder (GAD). It has received Breakthrough Therapy Designation from the FDA for MDD.
In the ARCHWAY trial, a Phase II study of SAGE-217 in adults with moderate to severe bipolar I/II disorder with a major depressive episode, patients showed a rapid and durable response to treatment and statistically significant improvement compared to baseline. About a third of subjects discontinued the study, however, for a variety of “social/personal reasons,” which the company notes is consistent with other studies in bipolar depression. No dropouts were made over adverse side effects.
In a trial of patients who didn’t respond to a single anti-depressant, SAGE-217 ran a post hoc analysis of 51 patients from the MDD-201B and ROBIN (PPD) trials. Patients receiving the drug had a 7.2-point greater decrease in Hamilton Rating Scale for Depression (HAM-D-17) compared to the placebo group at Day 15. At Day 42 or 45, the last day of the study, patients receiving the drug had a 4.9-point greater reduction in HAM-D-17 compared to placebo.
In the anxiety comparison, patients receiving the drug had a 4.6-point greater reduction in HAM-A score and 3.9-point greater reduction in HAM-A compared to placebo in the MDD-201B and ROBIN studies, respectively, and at Day 42, a 2.3-point greater reduction in HAM-A and a 5-point greater reduction in HAM-A, respectively, compared to placebo.
The company plans to also develop the drug for TRD but expects to discuss it in the future.
“We interpret these data as consistent with a very respectable signal suggesting a potential development opportunity in bipolar depression for SAGE-217,” the company’s Robert Lasser, head of late-stage development, said during the webcast. “However, that potential development opportunity is balanced against the depth of other work which is still possible, we think, within MDD.”
Which might be another way of saying post-hoc analyses don’t prove much, and the company will need to actually conduct prospective clinical trials in TRD. But from a practical strategy, there are advantages to TRD development. Sage’s Jonas noted that if the ongoing trial in MDD reads out equivocal results, that trial could permit filing of SAGE-217 in depression when coupled with the positive trial data in PPD. It would also make Sage more likely to get insurers to support their drugs over a variety of current generic offerings.
“We think it is the nearest term value driver and we believe that it will position SAGE-217, if and when it launches, to really be, we hope, one of the most valuable assets to be introduced in the major depression space,” Jonas said in the webcast.
It’s not an empty market, though. In March, Johnson & Johnson received approval for Spravato (esketamine) for treatment-resistant depression.
