Depression affects hundreds of millions of people worldwide. Relmada Therapeutics is working to develop a treatment for those with depression that does not respond to drugs currently on the market.
Relmada Therapeutics is a publicly-traded, specialty pharmaceutical company working at the clinical stage to develop dextromethadone (REL-1017) to treat a number of central nervous system (CNS) disorders. Prior to his work with Relmada, CEO Sergio Traversa, PharmD, MBA, had an impressive career in pharma and health care in the United States and Europe, as well as positions in financial analysis and investment in these areas.
One of Traversa’s earliest introductions to antidepressants was the work he did on the development and marketing of Prozac. He was also involved in the early development of Zyprexa and Cymbalta. More recently, Traversa co-founded Medeor, Inc., a spinoff company from Cornell University that is now Relmada. Traversa recently spoke with BioSpace about the work being done by Relmada to develop REL-1017 as a treatment for those with major depression that does not respond to currently available medications.
A New Approach
Traditional antidepressants such as Prozac, et. al., work on the uptake and modulation of neurotransmitters. This results in increased serotonin, norepinephrine and dopamine activity in the brain. It is this increase in neurotransmitter activity that brings about improvement. However, Traversa explains, it can take several weeks for these types of antidepressants to take effect. Since each specific antidepressant is not equally effective in every individual, it is sometimes necessary to try a number of different medications before one is effective. In some cases, none are effective, and the depression does not respond to treatment.
Dextromethadone (REL-1017) uses a different pathway to treat depression. Rather than working on the uptake and modulation of neurotransmitters, “REL-1017 increases the number of synapses in the brain,” said Traversa. As the number of synapses increases, the communication between them is increased. In preclinical studies conducted at Yale University, this activity ultimately resulted in more efficient communications among brain cells and improved cognition, as well as a rapid onset and longer-term antidepressant benefit in patients.
Clinical Evidence
In a clinical trial, patients who had not been helped by one to three previous antidepressant drugs were given REL-1017 as an adjunct to their existing antidepressant. Within the first four days, a statistically significant and clinically meaningful improvement in the patients’ depression symptoms was observed. These improvements continued for the remainder of the seven-day period that patients received treatment with REL-1017. Additionally, for the seven days following treatment, patients continued to experience improvements even though they had stopped taking REL-1017.
Traversa explains that this is significant because “existing antidepressants, while effective, only work in about one-third to half of the patients, meaning that many of the patients do not really benefit from these drugs. You have at least half, and more than half, of the patients who don’t really respond well or at all to the first treatment course or drug used.” The response of these patients to REL-1017 signals that an effective drug for their depression may be on the horizon.
Not the Only Drug Using this Pathway
Relmada’s REL-1017 will not be the only drug that uses this pathway. J&J has a product already in use, Spravato, that uses this pathway. Their drug has shown rapid-acting and long-lasting antidepressant effect. The major difference between Spravato and Relmada’s drug will be that J&J’s drug uses a nasal spray as the delivery mechanism, Traversa says. This spray is administered twice per week, in a clinical setting. An observation time of two hours is required after the dose. There are also driving restrictions until the day after the treatment. These requirements are in effect because Spravato can cause sedation, blood pressure changes, and dissociative effects in some patients. “The plan for REL-1017,” says Traversa, “is that it will be delivered in the form of a pill taken once a day at home.”
“We believe that REL-1017, if approved, has the potential to change the way depression is treated. This will change the lives of many people,” Traversa said. “We also believe that our proof-of-concept data from our Phase II trial of REL-1017 is very compelling. We are now focused on generating additional clinical data with REL-1017 and moving toward a registration program with the product expected to start at the end of this year.”
For those with major depression that does not respond to the treatments that are currently available, the clinical data indicates that REL-1017 may make a significant difference.
Published on BioSpace