Building an MBMA Framework to Support Developing New Neuropathic Pain Drugs

Model-Based Meta-Analysis (MBMA) is a growing methodology that leverages literature based and often external data to provide a quantitative framework to enable strategic drug development decisions. MBMA comparator models often include valuable pieces of information such as time, covariates, clinical trial efficacy and safety information.

Neuropathic pain (NP) is a pain initiated or caused by primary lesion(s) in the nervous system and is characterized by a presence of increased activity and dysfunction of peripheral sensory nerves within the CNS. The term neuropathic pain is used to categorize a collection of chronic pain syndromes such as diabetic peripheral neuropathy (DPN), post herpetic neuralgia (PHN) and fibromyalgia. The clinical development of novel neuropathic pain treatment is challenging and complicated by several factors including but not limited to patient reported outcomes, large placebo effects, varying baseline pain scores, varying methods for measuring response to treatments, lack of active comparator controls in development, and intrinsic factors.

Pain is subjective in nature. Therefore, use of an adequate instrument to measure the primary endpoint is critical to evaluate efficacy. Pain intensity or reduction in pain intensity is the fundamental measure of efficacy in analgesia. In addition, elements of trial design such as selection of appropriate primary and secondary endpoints, order of treatment, treatment duration, and allowed concomitant medications can influence a trial’s efficacy readout.

Many of these aspects make it difficult to compare trials head to head. MBMA provides a framework to compare treatments in silico that have not been studied in the same clinical trial and account for sources of potential variability.

In this webinar, Leticia Arrington (Merck) and Richard Franzese (Certara) discussed data considerations, analysis methods, and learnings from a recent network MBMA analysis of relevant endpoints in NP that will be used for general competitive landscaping questions to support Merck’s ongoing mission to develop better NP therapies.