Tackling the Challenges of Pain Through Science and Innovation By James Hackworth, Ph.D. President, Brand Division Tris Pharma

Alleviating the burden of acute and chronic pain has been a major focus of my work for over a decade. Throughout my career, I have been dedicated to advancing new ways to help the millions of people who navigate the stark reality of living with life-impacting pain that cannot be managed safely with existing products.

I’ve seen the consequences of chronic pain firsthand: from my seat as a researcher and executive, many conversations with patients and healthcare providers and, even more closely, from within my family. I witnessed the devastating toll that chronic pain had on my grandmother. She lived in rural Ohio, one of the regions of the country earliest affected and hardest hit by the opioid epidemic. My grandmother lived with severe osteoarthritis – a degenerative joint disease – and peripheral diabetic neuropathic pain for the last ten years of her life. Her treatment options were limited. Because she was taking blood thinners for her heart, she couldn’t take nonsteroidal anti-inflammatory drugs (NSAIDs), and she was afraid to turn to opioids after seeing their devastating effects on the lives of others around her. As a result, she endured severe and debilitating pain every day for years until she passed away in 2020 at the age of 89.

I’m heartbroken by how much my grandmother suffered, but as a result, I am more driven than ever to change the journey of others like her – the more than 50 million people in the United States who suffer from chronic pain with millions more suffering acutely.

Each September, Pain Awareness Month gives us an opportunity to not only shine a spotlight on the needs of people living with pain, but also take stock of our efforts to provide them with better solutions.

In this important, life-changing work, there is cause for optimism. We saw it at PAINWeek 2024, the largest summit of its kind held earlier this month. Through the educational sessions on cutting-edge topics and myriad of novel medical approaches on display, there is momentum building for a more promising future in pain management.

While the progress is encouraging, much work remains to change the enduring challenges of both chronic and acute pain. It’s work that is taking place against the backdrop of opioid addiction that continues to loom ominously throughout our nation and devastate lives from misuse, dependence and overdose. Exacerbating this crisis is the fact that therapeutic innovation has been largely at a standstill: there hasn’t been a novel mechanism in pain therapy approved by the FDA in over 30 years. The fallout is being felt throughout the lives of millions of individuals who suffer acutely from moderate-to-severe pain due to surgeries, illnesses, trauma and other injuries – or chronically through a myriad of conditions. It’s pain that can have detrimental physical, emotional and quality-of-life consequences, and today, too often their only choices are to suffer or risk becoming addicted to opioids.

Urgency for innovation

This year’s theme for Pain Awareness Month is “Changing the Pain Equation,” a timely call-to-arms for what those of us in the drug development community must continue to strive for on behalf of those who are counting on us. Our charge is to act with purpose and resolve in translating science into entirely novel therapeutic approaches, especially ones that could replace opioids that solely target the μ-opioid peptide (MOP) receptor and come with dangerous side effects.

Indeed, we must change the pain equation. That's where Tris is leading the way.

Our lead therapeutic candidate, cebranopadol, has the potential to address the unmet need for effective and safer pain management. Cebranopadol is the first-and-only dual nociceptin/orphanin FQ peptide (NOP) and MOP receptor (dual-NMR) agonist in clinical development, and it has demonstrated in clinical studies the capability to provide gold-standard pain relief with significantly less risk of physical dependence, abuse, respiratory depression and overdose. By leveraging the coactivation of the NOP and MOP receptors to regulate pain, we believe cebranopadol offers promise as a new kind of pain reliever.

Our body of clinical evidence to date underscores why our team is excited about its potential. Cebranopadol’s profile has been well-characterized in more than 30 efficacy and safety clinical trials involving over 2,000 patients to date. Data from these studies suggest that cebranopadol is effective at treating the most severe acute and chronic pain, including neuropathic pain, while reducing many of the harmful side effects seen in opioids and may have significantly lower risk of addiction and overdose. Today, we are moving with intention to successfully conduct two pivotal Phase 3 trials – ALLEVIATE-1 and ALLEVIATE-2 – evaluating the efficacy and safety of cebranopadol for the treatment of moderate-to-severe acute pain.

Acting together

In 2024, the International Association for the Study of Pain (IASP), the leading global organization supporting the study and practice of pain and pain relief, is proudly celebrating its 50th anniversary. On the IASP website you will find a wealth of information – just click on the link under “Working Together for Pain Relief Throughout the World.” I find this to be an ideal way to describe the job that lies ahead for all of us who are dedicated to improving the lives of people with pain.

Like my grandmother, they deserve the best from us.