Brain Awareness Week 2025
Brain Awareness Week is a global campaign held every March that aims to increase public support and excitement for brain science.
One of its core objectives is to educate the broader public about the impact of brain science on everyday lives. For many people, dealing with pain is an everyday struggle. Unfortunately, most therapeutic options for managing acute pain are associated with significant risks of dependence and addiction.
For the first time in over two decades, patients in the US will have an entirely new option available to manage acute pain – without the fear of addiction. On January 30th, Vertex Pharmaceuticals announced FDA approval of Journavx (suzetrigine), a highly selective voltage-gated sodium channel (NaV1.8) inhibitor. This is a major achievement for patients, healthcare providers, and society at large. In pharma, identifying a non-addictive pain medication has been a holy grail, particularly as the opioid epidemic continues its global path of destruction. CDC estimated that in 2022, an average of 224 people died each day from an opioid overdose in the United States. These numbers are staggering, both in terms of the lives impacted and the tremendous cost burden on healthcare and law enforcement. Moreover, fear of becoming addicted to opioids has deterred millions of patients who desperately need effective pain management, leaving them to suffer untreated. With the suzetrigine approval there is now new hope for these patients as well as for other non-opioid therapies in clinical development.
Expressed in primary sensory neurons, NaV1 channels have been appealing targets for drug development for decades. There are nine different subtypes, Nav1.1 through Nav1.9, each encoded by separate genes. To avoid off-target side effects, R&D efforts have focused on subtype selective inhibitors. In 2012, one of my first consulting projects at Deallus was the build of a competitive landscape of NaV1 inhibitors. In those days, NaV1.7 was the hot target for drug development, with several compounds already in mid-stage clinical development. But despite promising in vitro studies, selective NaV1.7 inhibitors have not yet succeeded in the clinic. Vertex’s suzetrigine is highly selective for NaV1.8; this subtype was not initially deemed as promising as NaV1.7, based on in vitro and genetic models, underscoring both the complexity of human biology and the need for large scale clinical trials.
Development of an effective non-opioid pain medication has proven incredibly challenging, with a crowded graveyard of failed programs including many NaV1 inhibitors. Like many neuroscience therapy areas, pain trial endpoints are largely subjective, and variable placebo response rates make it difficult to determine true effect sizes. Many programs fail due to side effects, notably anti-NGF monoclonal antibodies (developed by pharma giants Astra Zeneca, Eli Lilly, J&J, and Pfizer) which led to increased risks of joint damage. High potency nonsteroidal anti-inflammatory drugs have also been thwarted by safety issues. One bright spot in the broader pain landscape is migraine, which has seen the launch of several targeted therapies since 2018; however, the utility of these treatments is limited to headache pain.
But finally, Nav1.8 and suzetrigine emerged victorious, and pain medicine physicians, patients and drug development teams breathed a collective sigh of relief upon Vertex’s announcement.
Hopefully this milestone will motivate and inspire further investments in pain and other challenging therapy areas that have seen limited innovation in recent decades. Deallus has a track record providing decision support for pipeline programs across neuroscience, including pain, helping R&D and commercial development teams optimise their programs for success across early target identification, indication prioritization and development of pre-and post-launch in market strategies.
Neuroscience continues to be one of Deallus’ leading therapeutic areas, both in project volume and the expertise held by our consulting staff. We’ve had the privilege of partnering with many pharma organisations over the years as they navigate the challenges and complexities of drug development and commercialisation within neuroscience.
Author – Anna Scott, Senior Principal
March 2025