Quotient Sciences (Nottingham) partnered with Evecxia Therapeutics to support the development of EVX-101, an investigational adjunctive drug for depression and obsessive-compulsive disorder (OCD) responding inadequately to first-line antidepressants. The program is featured as part of a recent article with Drug Development & Delivery.
Depression affects an estimated 5% of adults globally, and in the US, depression diagnoses have risen 33% since 2013; twelve-month depression prevalence is 10.7%; and healthcare spending by a patient suffering from depression is twice that of the average patient. Unfortunately, less than one-third of patients respond adequately to first-line serotonin reuptake inhibitor antidepressants (eg, Prozac®) therapy. Current next-line options are limited by modest efficacy and safety concerns. For patients who do not respond adequately to first-line antidepressants, new next-line options are urgently needed.
EVX-101 is a first-in-class drug acting via Serotonin Synthesis Amplification. Using Quotient Sciences’ Translational Pharmaceutics® platform, the team developed and manufactured the drug product and conducted an adaptive clinical study to optimize performance against the target product profile.
A gastro-retentive (GR), bilayer modified-release (MR) EVX-101 tablet formulation combining 5-hydroxytryptophan (5-HTP) — the natural immediate serotonin precursor — with low-dose carbidopa (enhances 5-HTP’s bioavailability) was developed and manufactured for clinical testing. This formulation approach effectively addressed the inherent challenges of 5-HTP’s short half-life, narrow absorption window, and low bioavailability.
The two-part clinical study involved a sipping protocol to confirm the GR strategy and to define the carbidopa dose range (Part 1) and a formulation optimization study using a 2-dimensional design space to vary the release rate of the two drugs and the GR retention time (Part 2). The formulations were radiolabeled with not more than 1 MBq 111indium allowing gamma scintigraphy to be used to assess in vivo formulation performance. The optimized formulation was then progressed to a Phase I program, which included single ascending dose (SAD) and multiple dose titration (MAD) study in healthy volunteers treated with escitalopram.
To learn more about the program and significant time savings achieved compared to conventional formulation optimization strategies, read the full article on Drug Development & Delivery.