Depression affects more than 264 million people globally and 17 million adults in the US. Depression is characterized by persistent low mood or lack of pleasure in previously rewarding or enjoyable activities. Depression is associated with significant impairments in all aspects of life, from vocational and scholastic performance, to social and familial relationships. Depression is associated with increased risk of diabetes, obesity, cancer, and cardiovascular disease, and a reduced life span.
Depression is diagnosed when a person experiences depressed mood and/or loss of interest or pleasure in daily activities for at least 2 weeks and has additional specified symptoms such as problems with sleep, eating, energy, concentration, or self-worth.
If not treated to remission, depression can be devastating for patients and their families. Unfortunately, the efficacy of first-line antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs, e.g. Prozac® [fluoxetine]) and serotonin-norepinephrine reuptake inhibitors (SNRIs, e.g. Cymbalta® [duloxetine]) is moderate at best. While some patients do respond well, fully two-thirds of patients fail to achieve adequate antidepressant response to first-line antidepressants. Switching to a different first-line antidepressant or an atypical antidepressant (e.g. Wellbutrin® [bupropion]) provides better efficacy to only a small minority of patients.
Next-line treatment options have modest additional efficacy, and often a high side-effect burden. To date, only one oral drug class, atypical antipsychotics (e.g Abilify® [aripiprazole]), have been approved to treat depression as adjunctive therapy to SSRIs/SNRIs; but, most depression patients do not benefit from adjunctive atypical antipsychotics. And troubling side-effects include weight gain, diabetes, and motoric anomalies. Newer ketamine-based antidepressants provide significant relief to a subset of patients. Yet, the drugs have modest overall efficacy, and are limited by a requirement for in-clinic parenteral administration, limited access, schizophrenia-like side-effects, abuse potential, and high cost.
More effective and safer treatment options are urgently needed for the many depression patients not responding adequately to first-line SSRI/SNRI therapy.
Evecxia Therapeutics is developing adjunctive EVX-101 for depression responding inadequately to first-line SSRI/SNRI monotherapy. EVX-101 will amplify the brain’s natural serotonin production, thereby synergizing with the SSRI/SNRI in promoting brain serotonin neurotransmission and augmenting the antidepressant response.
In 2018 more than 48,000 people died by suicide in the US; 1.4 million people attempted suicide. In young people, suicide was the 2nd leading cause of death. US suicide rates have increased 35% since 2000. Suicide has risen to epidemic levels and is a national emergency in the US. Likewise, in the European Union, 56,000 people died by suicide in 2018.
Unfortunately, there are no drug treatments for suicidality approved by the FDA or European Medicines Agency. New treatments for treating acute suicidal crisis and for preventing future suicides are critical for combatting the suicide emergency.
Evecxia Therapeutics is developing EVX-301—a proprietary up to 24h infusion of 5-hydroxytryptophan (5-HTP)—to treat patients hospitalized for acute suicidal ideation crisis. EVX-301 is designed to rapidly amplify endogenous brain serotonin, which, in turn, could rapidly ameliorate suicide-related affective states and behaviors.
The human suicidal ideation behavioral phenotype is characterized by impulsivity, aggression, low mood, and feeling socially disconnected. Various clinical studies report that acutely elevating extracellular serotonin can ameliorate impulsivity and aggression and improve mood and social connectedness. Thus, acute extracellular serotonin elevation represents a putative anti-suicidal pharmacology. EVX-301 will elevate extracellular serotonin with an optimized, personalized profile, which, everything equal, could treat acute suicidal ideation crisis.