Make a joint effort to fight osteoarthritis of the knee

As anyone with osteoarthritis of the knee (OA) knows, it hurts a lot. It is one of the most common forms of arthritis, affecting almost a quarter of a million people here, around 18 million Europeans and 14 million people in the United States. Around one in four adults in Ireland over the age of 60 have osteoarthritis of the knee.

“Osteoarthritis of the knee is a painful, progressive and incurable disease that affects millions of people worldwide, but there have been no disruptive breakthroughs in its treatment for 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 cutting-edge new treatment for the disease.

Most oral medications and injectable steroids for the disease have serious potential side effects if used for prolonged periods. these include organ damage, addiction, and cartilage destruction, says Liddy.

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

Relevium is focused on the development of new peptide gel-based biotherapies to treat chronic diseases. Knee osteoarthritis is the starting point of the business; however, its treatment will also work for osteoarthritis of the hip – which is another huge potential market.

‘Sustainable’

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

Relevium’s injectable hydrogel is composed of a new peptide bound to a natural polymer. “The polymer base alone lubricates and helps restore the mechanical properties of joint fluid.”

The addition of 315y peptide gives the product its disruptive pharmacology by blocking pain signals from traveling through the nerves to provide lasting pain relief and also by promoting and protecting cartilage-producing cells, thereby reducing the progression of disease. Additionally, the hydrogel has an excellent safety profile and lacks the adverse side effects seen with steroids and many pain relievers,” adds McDermott.

Peter Schmidt, clinical assistant professor of anesthesiology, perioperative medicine and pain medicine at Stanford University and Stanford University Hospital in the United States, is excited about Hydrobloc’s potential to improve quality life of patients.

“Recent studies suggest that the worldwide prevalence of knee osteoarthritis is approaching 23% in people aged 40 or older. Despite this alarming prevalence, non-surgical treatment options remain quite limited, with little innovation in recent decades. Relevium’s approach to osteoarthritis pain has the potential to revolutionize the way we clinicians treat this debilitating condition,” he says.

“If we can provide patients with a localized therapy that provides long-lasting efficacy and avoids the adverse effects of corticosteroids, we can delay surgical treatment for younger patients and significantly improve the quality of life for patients who are not candidates for surgery. “, adds Schmidt.

direct benefit

In addition to the direct benefit to the patient, this approach could result in significant healthcare cost savings by avoiding or delaying surgery for osteoarthritis. “It’s very exciting and I know the medical community will be eagerly awaiting the results of the clinical trials,” he says.

Hydrobloc will compete with steroid, hyaluronic acid and stem cell injectables currently produced by major pharmaceutical companies. The knee osteoarthritis market is growing at a compound annual growth rate of 10%, with the global joint pain market estimated at €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 provide only transient relief, limiting their use. to three to four injections a year,” says Liddy.

“There are many injectable hyaluronic acid products on the market which, although safe, have limited effectiveness and the American Association of Orthopedic Surgeons no longer recommends their use for osteoarthritis of the knee.

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

Liddy says that patients with osteoarthritis suffer from chronic pain for an average of 28 years from initial diagnosis, and inadequate pain management is directly linked to quality of life. A third of people over 45 with the disease suffer from high levels of depression and sleep deprivation. As symptoms worsen, more than 60% will develop at least one comorbidity such as high blood pressure or diabetes. As their movements become more restricted, these comorbidities increase.

“There is currently no way to prevent the progression of the disease and no effective and lasting treatment for pain is available, leaving more than 68% of patients dependent on frequent medication. This again underscores the urgent need for new treatment options for this debilitating disease,” says Liddy.

Named inventor

Liddy, who comes from a background in chemistry and holds a PhD in biochemical engineering, has worked on a variety of life science projects at Roche, Boston Scientific and Cook Medical and is the named inventor on 20 publications of patents. She is also an alumnus of the Stanford Biodesign Affiliate Program at NUI Galway. McDermott, who has a background in molecular design, clinical trials and regulation, holds degrees in pharmacy and veterinary medicine and a doctorate in biomedical engineering. They created Relevium in 2019.

An interesting part of creating Hydrobloc is the patient-centric approach the team took to developing the product. This means that the voices of people living with the disease are heard and used to inform research with the goal of creating a solution that not only meets clinical needs, but also positively impacts quality of life and outcomes for patients. patients.

“Besides the disruption to people’s lives caused by knee osteoarthritis, it also represents a huge health cost,” says Liddy. “It currently costs over $185 billion a year in the US for direct medical care costs and a similar amount in Europe, and the market/costs are growing rapidly due to the high prevalence of osteoarthritis of the knee in geriatric and obese populations”.

So far, Hydrobloc’s development costs have been around €1.35 million and have been supported by Science Foundation Ireland, EIT Health Headstart and the European Research Council.

“In 2021, we received the top prize from the €7 million Disruptive Technology Innovation Fund alongside our collaborators NUIG, Duffy Lab and HiTech Health,” says Liddy. “In December, we were awarded a transition grant from the European Innovation Council worth €2.4 million. The magnitude of these rewards clearly validates the urgent need for new treatments.

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

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