Psychiatric Disorders

Sage is seeking to shift how certain mood disorders are understood and treated.

Sage is exploring new disease pathways for certain psychiatric disorders where there is a high unmet need for additional treatment options. We are working to understand the underlying mechanisms for numerous disorders of the brain and central nervous system (CNS) to help us develop therapies that may address current treatment gaps for patients.

We focus our research and development efforts on modulation of GABA and NMDA receptors, two critical neurotransmitter systems that have responsibility for information flow within the intricate circuits of the brain and central nervous system. Both GABA and NMDA systems contribute significantly to regulating CNS function. However, dysfunction in these two systems is known to be at the core of numerous psychiatric disorders. Navigating these complex circuits is a challenge, but a welcome opportunity for the teams at Sage as we seek to provide new treatments for patients.

We are using our unique development approach to systemically evaluate our drug candidates in a range of psychiatric disorders:

Postpartum Depression

Postpartum depression is the most common medical complication of childbirth, estimated to affect 8-20% of new mothers in the U.S., varying by state with an overall average of 11.5%.1-5 During pregnancy, levels of certain hormones rise and then rapidly fall after giving birth. These hormone shifts may put some women at risk for developing this serious disorder.

Postpartum depression can have devastating consequences for a woman and for her family, which may include significant functional impairment, depressed mood and/or loss of interest in her newborn, and associated symptoms of depression such as loss of appetite, difficulty sleeping, worry or feeling overly anxious, motor challenges, lack of concentration, loss of energy and poor self-esteem.

There are no medications specifically approved to treat postpartum depression. A new drug application for our lead product candidate, ZULRESSOTM (brexanolone) injection, as a treatment for postpartum depression is under review with the FDA. We are also developing another product candidate, SAGE-217, in the treatment of postpartum depression as part of a broader depression program.

Major Depressive Disorder

Major depressive disorder is a common but serious mood disorder, often affecting how a person feels, thinks, and handles daily activities. Generally thought of as a chronic condition, it’s characterized by episodes of depressed mood, feelings of hopelessness, anxiety, loss of energy and sleeping difficulties. Major depressive disorder can be life-threatening. Approximately 16 million people in the U.S. suffer from major depression each year.6

While antidepressants are widely used for treatment, results from large scale studies suggest the need for additional treatment options.7,8 GABA modulation is being studied as a new possible mechanism of action for treating episodic depression.9-11 We are evaluating SAGE-217, an oral compound, as a potential therapy for this disorder.

Bipolar Disorder

Bipolar disorder is a chronic, episodic illness characterized by both manic and depressive episodes. It is associated with significant disability worldwide, as well as increased risk for other mental health disorders. Diagnosis can be difficult—most patients seek medical attention in the depressed phase of illness, making it challenging to distinguish from major depressive disorder. Bipolar depressive episodes are severely debilitating, yet there are currently few treatment options. We are evaluating SAGE-217 as a potential therapy for bipolar disorder.

References

References

  1. Ko JY et al. MMWR Morb Mortal Wkly Rep. 2017;66:153-158
  2. DeSisto CL et al. Prev Chronic Dis. 2014;11:E10;
  3. Centers for Disease Control and Prevention. Data on Selected Pregnancy Complications in the United States. 2017. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pregnancy-complications-data.htm. Accessed June 4, 2018
  4. Knight M et al. BMC Pregnancy Childbirth. 2009;9:55
  5. Reddy UM et al. Am J Obstet Gynecol. 2015;213:538
  6. Nat. Inst. of Mental Health website, 2015; Available at https://www.nimh.nih.gov/health/statistics/prevalence/major-depression-among-adults.shtml.
  7. Trivedi MH, et al., Am J Psychiatry, 2006,163:1, 28-40
  8. Rush AJ et al., Am J. Psychiatry, 2006,163:11, 1905-1917
  9. Uzunova et al., PNAS, 1998
  10. Luscher et al, Molecular Psychiatry, 2011
  11. Schule et al, Progress in Neurobiology, 2014