New publication: Targeting for Success: Demonstrating Proof-of-Concept with Mechanistic Early Phase Clinical Pharmacology Studies for Disease-Modification in Neurodegenerative Disorders

While there have been successes in neuropharmacology, most central nervous system pharmaceutical approaches treat symptoms rather than disease cause. Such symptomatic treatments can be very successful at suppressing disease symptoms at first, however, the effects eventually diminish over time and do not stop disease progression. Hence, there is an urgent need for better treatments that can slow or stop disease progression of neurodegenerative disorders (NDDs), especially since the burden of these debilitating diseases on patients and society is on the rise as populations age. However, the clinical failure rate for such disease-modifying treatments for NDDs has been nearly 100% to date, with many compounds failing in expensive and time-consuming phase 2 and 3 trials for lack of efficacy.

Fortunately, considerable progress is being made in the development of biomarkers for NDDs that cannot only help diagnose or track progression of NDDs, but can also be used as tools during clinical development to demonstrate central exposure, (peripheral) target engagement and functional responses to guide dosing-decisions. The use of such biomarkers can offer an indirect yet relatively quick strategy to confirm (peripheral) target and pathway-engagement and provide early proof-of-concept in short-duration mechanistic early-phase trials in both healthy volunteers and patients. This quick win/fast fail approach can increase R&D productivity and help guide dosing-decisions for maximizing success rates in later stage trials.

We have critically reviewed the use of pharmacological and mechanistic biomarkers in early phase clinical trials of disease-modifying treatments in NDDs, and propose a roadmap for providing early proof-of-concept to increase R&D productivity in this field of high unmet medical need. You can read our paper here.

This paper is an excellent example of CHDR’s mission to overcome drug development challenges by gaining in depth insight into the pharmacology of new compounds at the earliest stages of development by incorporating relevant biomarkers. Equipped with a state-of-the art biomarker research laboratory and a talented method development team, we are passionate about developing and implementing biomarkers for specific mechanisms of action. To support the study of a wide variety of mechanisms and effects, we offer a diverse range of methods and tools, such as the NeuroCart®, the PainCart® or Transcranial Magnetic Stimulation (TMS) coupled with electromyography (EMG) and electroencephalography (EEG). Other methods we offer can be found here.