Innovating for the invisible ailment: the ASX-listers combatting chronic pain

Imagine living with a persistent, debilitating discomfort for weeks, months, or even years on end. An ailment that impacted your work and livelihood. Unfortunately, this scenario is far from a stretch of the imagination for more than three million Australians who live with some form of chronic pain. Doctors have investigated chronic pain for years, but the recent emergence of long COVID — where those infected with COVID-19 experience symptoms long after their diagnosis — has brought further attention to this space. That’s because one of long COVID’s major symptoms is musculoskeletal pain — a condition experienced by many chronic pain sufferers who are often limited to managing their discomfort with prescription opioids. Because of the risks associated with these analgesics, ASX-listed biotechs and pharmaceutical companies are hard at work to develop better treatments for chronic pain sufferers. With everything from a nerve repair candidate to cannabinoid formulations in the works, it’s possible a homegrown solution could lead to better patient outcomes in a sector where the standard of care is often expensive, addictive and has only fleeting efficacy. The rapid rise of long COVID As the world tackles COVID-19, healthcare professionals are increasingly dealing with the long-term effects of the coronavirus pandemic, namely in the form of long COVID. Although COVID-19’s symptoms are supposed to be short-term, it’s estimated around one in three sufferers experience indications beyond the two-week incubation period, while roughly 10% of those diagnosed have symptoms for 12 weeks or more. The data on long COVID is in its early stages, but experts are already calling for healthcare reform to better manage the long-term condition. Martin Hensher, associate professor of health system financing and organisation at the Institute for Health Transformation and deputy director of Deakin University’s Health Economics program, says long COVID is similar to a number of other long-term chronic conditions. “Most directly, it does seem to share quite a lot of similarities with myalgic encephalomyelitis chronic fatigue syndrome,” he said. “The Australian healthcare system — and pretty much all healthcare systems — are actually just not very good at dealing with these long-term chronic conditions, for which there is not a definitive, straightforward treatment.” With the world’s eyes trained on the pandemic, could COVID-induced reform lead to better healthcare outcomes for people with chronic pain? Australia’s chronic pain landscape Chronic pain is a common condition down under, with one in five Australians over 45 living with some form of persistent physical pain. But beyond the physical symptoms, Painaustralia CEO Carol Bennett believes it’s important to consider the links between chronic pain and mental health conditions. “Chronic pain is a major contributor to mental health that has not been adequately addressed. Almost half of those living with chronic pain experience significant mental health problems, including depression, anxiety and increased suicidality. “It’s time to look at how we target those who live with pain and mental health problems, a population that seems largely invisible within existing mental health services.” Sadly, the number of chronic pain sufferers in Australia is set to rise. Deloitte Access Economics predicted in 2019 that 5.23 million Australians would be living with a chronic pain condition by 2050. With more cases than ever before, it’s imperative those living with chronic pain have access to effective, safe treatments. So, what’s the problem with opioids? Opioids and addiction The primary issue with opioid treatments is simple: they’re addictive. And while the drugs can help manage chronic pain, University of Florida professor Robert Caudle says these analgesics aren’t without their side effects. “Unfortunately, patients rapidly develop tolerance to opioids, which significantly reduces their effectiveness for chronic therapy. “Because of this as well as their addictive nature, potential for abuse and overdose, and side effects such as constipation, opioids are less than ideal agents for treating chronic pain. “It is critical that we find alternatives. But that’s easier said than done.” It’s clear opioids have their downsides. But what if there was a way to make these analgesics more effective? Optimised drug delivery One ASX-listed business believes the problem isn’t with opioids, but the way they are taken. Avecho Biotechnology Ltd (ASX:AVE) is interested in reformulating treatments with its proprietary drug delivery platform, boosting the efficacy and safety of candidates. In the past, the biotech has worked on transdermal opioid patches, which administer the analgesic through a patient’s skin instead of an oral pill. Avecho CEO Paul Gavin believes it’s a way to avoid a “seesaw of opioids” in the bloodstream — triggering an opioid’s negative side effects. Another ASX-lister working along these lines is SUDA Pharmaceuticals Ltd (ASX:SUD). The Perth-headquartered drug delivery company is focused on increasing the bioavailability of medications by reformulating them as an oral spray. While the idea has wide-reaching implications and is currently being developed as an insomnia treatment, SUDA’s technology could also be used to effectively manage chronic pain. Ultimately, if the bioavailability of an opioid is increased, the analgesic could work its magic without the addictive and dangerous side effects. Chronic pain affects over three million Australians, the vast majority of which are of working age. Treating chronic pain at the source While some companies are investigating ways to improve the efficacy of existing pain management drugs, other ASX-listed entities are interested in treating injuries linked to chronic pain. Orthocell Ltd (ASX:OCC) is one such business: the regenerative medicine company is focused on improving mobility and relieving pain by repairing a patient’s damaged nerve tissue. Last year, the ASX-lister tested its CelGro® nerve repair candidate on quadriplegic patients, with the 12-month data indicating more than three-quarters of the nerve repairs lead to functional recovery. Orthocell managing director Paul Anderson says CelGro can also address chronic pain as it works to repair damaged nerve tissue. “What we see in this nerve model is that these patients often have chronic neuropathic pain after the injuries, which caused them to be prescribed with some fairly heavy painkilling drugs, including opioids. “In the data we've collected, we're able to demonstrate that patients who were on opioids prior to surgery have significantly reduced the use of those opioid medicines. “From a conceptual perspective, we're addressing chronic injuries via a repair process which is more sophisticated than what was previously possible.” Paradigm Biopharmaceuticals Ltd (ASX:PAR) is another company seeking to treat chronic pain at the source, with a clinical pipeline focused on knee and hip osteoarthritis. The biopharma company is currently investigating how Pentosan Polysulfate Sodium (PPS) can be repurposed to treat conditions like osteoarthritis and bone marrow lesions, chronic heart failure and alphaviral arthritis. Paradigm currently has a program in front of the US Food and Drug Administration and is seeking clearance to start a phase three US study in around 1,000 patients. When it comes to treating pain, company founder and chief executive officer Paul Rennie believes innovation is key. “We’ve put men on the moon and done amazing things in science … and yet, when it comes to common diseases like osteoarthritis, we’re grappling with drugs we now know not to be recommended. Where's the innovation?” Could CBD hold the key? Medicinal cannabis has garnered significant traction over the last five years, and there are some early indications the plant-based ‘wonder drug’ could also be used in the chronic pain space. However, the initial evidence is anecdotal, meaning clinical data is key in proving just how effective cannabinoid formulations could be against chronic pain. Avecho Biotechnology CEO Paul Gavin said: “It’s a bit up in the air whether medicinal cannabis will actually be an analgesic and reduce pain, or whether it will be an adjunct therapy that helps patients cope with the pain better. “[Medicinal cannabis] is kind of like hope in a jar at the moment. And as more biotechs and pharmaceutical companies spend time working on it, we're basically going to put a red pin through three-quarters of what's being prescribed for. “We’ll end up with a much more true treatment group so that we can actually prescribe the stuff to patients.” While the world waits for more concrete data on medicinal cannabis treatments and their impact on chronic pain, ASX-listers are creating formulations that could one day come in handy. Zelira Therapeutics Ltd (ASX:ZLD) is exploring whether cannabinoid formulations can be used as an alternative treatment for chronic pain, reducing a patient’s reliance on opioids. On Monday, the company announced it would go head-to-head with big pharma in a US clinical pain trial just months after licensing its cannabinoid formulation to Levin Health Limited for a study into sports-related chronic pain in retired athletes. Cannabinoid formulations could help manage chronic pain, but more clinical evidence is required. An individualised approach to patient care When it comes to caring for people with chronic pain, Emyria Ltd (ASX:EMD) believes treatment should be as individualised as its patient cohort. As part of its care system, the company runs a series of brick-and-mortar clinics, where two-thirds of Emyria patients seek care to treat their chronic pain conditions. Recently, the healthcare stock set out to validate clinical data from one of its personalised care plans for opioid users in a world-first data linkage project. Results from two research and analytics firms proved that, on average, opioid consumption reduces after a patient starts care at Emyria’s Emerald Clinics following 12 months of steady-state opioid use. Speaking to the validation, Emyria managing director Dr Michael Winlo said the results were promising. “It gives us a lot of confidence, both in the quality of our data, but also in the effectiveness of our care model, which is largely personalised for every patient.” “Now, we're in a position to ask questions like ‘what happens to opioid use when [patients] stop taking medicinal cannabis — does that climb back up again?’ ‘Are there additional things we can do to further improve patients reliance on opioids?’ and ‘Can we look at building synthetic control cohorts?’.” The future is bright: an emphasis on innovation Although pain management options for chronic pain sufferers are currently limited, it’s clear that several public companies see the need for innovation. There’s rising demand for innovation and reform surrounding how we treat chronic pain. But as research in this field continues to grow, further investment is needed to develop new treatments for a condition that impacts millions of Australians. According to the National Health and Medical Research Centre, between 1996 and 2016, research aimed at understanding pain attracted just $133 million in funding, while cardiovascular disease research garnered $687 million in equity in a quarter of that time. If the reform health experts are calling for is to be effective, renewed interest and investment in the chronic pain landscape is required. The question, then, becomes: how will these ASX-listed businesses continue to answer the call for innovation, and where will their clinical pipelines lead?