Phase 3 enabling program for a small molecule in treatment resistant depression and major depressive disorder
Clinical depression is a chronic, recurring psychiatric illness that, according to Datamonitor, afflicts more than 12.5 million adults in the U.S. It is a disabling condition that adversely affects the patient’s quality of life, eating and sleeping habits, and overall health. Currently, clinical depression is treated with various antidepressants but their use is associated with a number of significant limitations. First and foremost, antidepressants have many undesirable side effects, including sexual dysfunction, fatigue, and weight gain. Moreover, many patients only partially respond to antidepressant therapy while some do not respond at all. In this sub-set of patients who do not respond to antidepressants (treatment resistant depression or TRD), the treatment alternatives are limited. It is this group of TRD patients which our research primarily aims to benefit.
The prevailing therapy for TRD is electroconvulsive therapy, or ECT, which involves a patient first being anesthetized and then having electric currents passed through the brain. Although deemed effective, ECT is known to cause memory loss and confusion in some patients. Through our research program with [Redacted] we seek orally available therapeutic alternative to ECT that is efficacious but without significant side effects. In addition, we believe that [Redacted] could be a novel treatment for patients with MDD devoid of the undesired side-effects of existing treatments.
The potential effectiveness of our drug is premised on two recent discoveries in the field of neuroscience: that it is possible to create new neurons in the adult human brain, and that these new neurons are necessary for antidepressants to work. Our earlier research has shown, in a laboratory setting, that [Redacted} causes human stem cells to grow into new neurons. Additionally, [Redacted] yields positive results in animal depression models. Further, our [Redacted] Phase I trials to date reflect a promising safety profile in humans. Therefore, we believe that [Redacted] has the potential to be a new standard of care for the treatment of TRD and second-line therapy for MDD patients who do not respond adequately to current treatments or cannot tolerate their side effects.
Depression or major depressive disorder (MDD) is a major public health concern in terms of its prevalence and cost to society. It is associated with significant impairment and decreased productivity. It can lead to changes in immune and endocrine function, increasing susceptibility to physical disease. The proposed research will evaluate the efficacy of an oral medication, [Redacted], for the treatment of MDD with a primary emphasis on patients who are unresponsive to current therapies (treatment resistant or TRD). Current treatments for TRD are invasive, require inpatient care and are accompanied by undesirable side effects such as psychosis and short-term memory loss.
The primary goal of the proposed research program with [Redacted] is to develop an efficacious and less costly therapy for TRD patients without the significant side effects. A secondary goal is to provide a therapeutic alternative for MDD patients who do not adequately respond to current therapies or who cannot tolerate their side effects. The realization of these goals will lead to significant health, social and economic benefits in California. The World Health Organization estimates that depression is the leading cause of disability worldwide. The symptoms of depression impair work, social interaction and personal functioning. Depression can lead to changes in health behaviors such as increased smoking, high-risk sexual activities and increased risk of sexually transmitted diseases, particularly among the young, with major economic consequences. In the most serious cases, it can lead to long-term, costly inpatient care. An NIMH-sponsored analysis (2009), found that patients diagnosed with depression incurred ~ $22,960 in annual health care costs, while those without depression incurred ~ $11,956 in costs.
If the [Redacted] program achieves it goals, it has the potential to radically improve patient care and reduce the negative impact of depression on quality of life factors such as family life, interpersonal relationships, job retention and performance. It also has the potential to reduce the significant economic burden to the State resulting from the deleterious, long-term health consequences of depression. The Substance Abuse and Mental Health Services Administration estimates that in 2003 approximately 58% of all mental health care, which includes depression, were paid by publicly funded programs. An effective therapy may also reduce the indirect costs associated with depression such as disability benefit payments and loss of earnings and tax revenue associated with those earnings. Finally, this grant helps to foster the further development of a robust and sustainable life science community in [Redacted] by providing jobs and funding to support the research outlined. Over time, [Redacted] has the potential to generate significant revenue which will not only increase the tax base for California but will also allow for further investment in new technology.