Relevium: Making a joint effort to tackle knee osteoarthritis

As anyone who suffers from knee osteoarthritis (OA) knows, it hurts like hell. It is one of the most prevalent forms of arthritis, affecting nearly a quarter of a million people here, an estimated 18 million Europeans and 14 million people in the US. Roughly one in four adults in Ireland aged over 60 has knee osteoarthritis.

"Knee osteoarthritis is a painful, progressive and incurable disease that affects millions of people worldwide, yet there have been no disruptive breakthroughs in its treatment in over 50 years," says Dr Alison Liddy, co-founder with Dr Barry McDermott of the biopharmaceutical start-up Relevium. The company has developed Hydrobloc, a new cutting-edge treatment for the condition.

Most oral medications and injectable steroids for the condition have serious potential side-effects if used for prolonged periods of time; these include organ damage, dependency and cartilage destruction, says Liddy.

“The complexity of knee osteoarthritis also means treatments should have multiple complementary and synergistic actions to be effective. However, current treatments have only one and are inadequate, giving limited, short-term relief. With Hydrobloc the therapeutic effect is expected to result in six-month intervals between injections. Up to recently it was believed knee osteoarthritis was a disease of wear and tear. The latest evidence shows it to be a complex whole-organ disease, affecting multiple tissues, with different disease patterns for different patients.”

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Relevium is focused on developing novel peptide gel-based biotherapeutics to address chronic diseases. Knee osteoarthritis is the company’s starting point; however, its treatment will also work for hip osteoarthritis – which is another huge potential market.

‘Long-lasting’

“Hydrobloc is a first-of-a-kind treatment that offers targeted, long-lasting pain relief without the side-effects of oral medication,” McDermott says. “Our proprietary formulation makes it the first and only knee osteoarthritis treatment that provides long-lasting effective pain relief and supports the protection and health of the damaged knee over time.”

Relevium’s injectable hydrogel is composed of a novel peptide linked to a naturally occurring polymer. “The polymer base alone lubricates and helps restore the mechanical properties of the joint fluid.”

The addition of peptide 315y gives the product its disruptive pharmacology by blocking pain signals from travelling in nerves to give long-lasting pain relief and also by promoting and protecting cartilage-producing cells, reducing disease progression. In addition, the hydrogel has an excellent safety profile and does not have the damaging side-effects seen with steroids and many pain medications,” McDermott adds.

Peter Schmidt, clinical assistant professor of anaesthesiology, perioperative and pain medicine at Stanford University and Stanford University Hospital in the US, is enthusiastic about Hydrobloc's potential to improve the quality of life for patients.

“Recent studies suggest the worldwide prevalence of osteoarthritis of the knee approaches 23 per cent in individuals 40 years of age or older. Despite this alarming prevalence, non-surgical treatment options remain quite limited, with little innovation over the past few decades. Relevium’s approach to osteoarthritis pain has the potential to revolutionise how we as clinicians treat this disabling condition,” he says.

“If we can provide patients with a localised therapy that provides durable efficacy and avoids the adverse effects of corticosteroids, we can delay operative treatment for younger patients, and vastly improve quality of life for patients who are not surgical candidates,” Schmidt adds.

Direct benefit

Besides the direct benefit to the patient, this approach could lead to significant healthcare cost savings by avoiding or delaying surgical intervention for osteoarthritis. “It’s all quite exciting and I know the medical community will be looking forward to the clinical trial results,” he says.

Hydrobloc will compete with the steroid, hyaluronic acid and stem cell injectables currently produced by the large pharma companies. The knee osteoarthritis market is expanding at a compound annual growth rate of 10 per cent, with the global joint pain market estimated to be worth €6.5 billion by 2026.

“All steroid products offer the same value proposition of fast -acting pain relief. They are very effective as anti-inflammatory agents. However, steroids damage cartilage and only give transient relief, limiting their use to three to four injections a year,” Liddy says.

“There are numerous hyaluronic acid injectable products on the market which, while safe, have limited efficacy and the American Association of Orthopaedic surgeons is no longer recommending their use for knee osteoarthritis.

“Despite this lack of clinical efficacy, the absence of other options for clinicians means hyaluronic acid products still represent a billion-euro market. There are several companies trying to develop stem cells for pain and regeneration which may show promise, but to date the clinical evidence for these products for knee osteoarthritis is still a subject of debate.”

Liddy says that patients with OA suffer from chronic pain for an average of 28 years from initial diagnosis, and inadequate pain management is directly related to quality of life. One-third of people over the age of 45 with the condition suffer high levels of depression and sleep deprivation. As the symptoms worsen, over 60 per cent will develop at least one co-morbidity such as high blood pressure or diabetes. As their movement becomes more restricted, these co-morbidities increase.

“There is currently no means to stop the disease from progressing and no long-lasting effective pain relief treatment available, leaving over 68 per cent of patients reliant on frequent medication. This again underlines the urgent need for new treatment options for this debilitating disease,” Liddy says.

Named inventor

Liddy, who comes from a chemistry background and has a doctorate in biochemical engineering, has worked on a variety of life sciences projects at Roche, Boston Scientific and Cook Medical and is the named inventor on 20 patent publications. She is also a former participant in the Stanford Biodesign-affiliated programme at NUI Galway. McDermott, who has experience in molecular design, clinical trials and regulation, has degrees in pharmacy and veterinary medicine and a PhD in biomedical engineering. They set up Relevium in 2019.

An interesting sidebar to the creation of Hydrobloc is the patient-centric approach the team took to developing the product. This means that the voices of those living with the disease are heard and used to underpin the research in an effort to create a solution that doesn’t just meet clinical needs but also has a positive impact on quality of life and patient outcomes.

"Apart from the disruption caused to people's lives by knee osteoarthritis, it also represents a huge healthcare cost," Liddy says. "It is currently costing over $185 billion a year in the US for direct medical care costs and a similar amount in Europe, and the market/costs are rapidly expanding due to the high prevalence of knee osteoarthritis in the geriatric and obese populations."

So far, development costs for Hydrobloc have been in the region of €1.35 million and this has been supported by Science Foundation Ireland, EIT Health Headstart and the European Research Council.

"In 2021, we were awarded the largest disruptive technology innovation fund award of €7 million alongside our collaborators NUIG, Duffy Lab and HiTech Health," Liddy says. "Then in December we secured a European Innovation Council transition grant worth €2.4 million. The scale of these awards clearly validates the urgent need for new treatments."

Both grants start this year and will support further product development and a phase one clinical trial. Relevium is on course to secure FDA approval in the US and launch Hydrobloc in 2028. The company is now seeking to raise €6 million in a recently opened investment round.