Healthy articular cartilage has a protective function in the knee by cushioning it against movement and ensuring that leg bones do not directly rub up against each other. The ageing process causes cartilage degeneration that may lead to osteoarthritis (OA). OA of the knee is known as gonarthrosis and is an important cause of disability and pain worldwide. As cartilage damage cannot be reversed, existing treatments such as hyaluronic acid injections are palliative focusing on relieving the pain and slowing down disease progression.
An innovative treatment that restores cartilage damage
The EU-funded RHYP project developed an innovative treatment for gonarthrosis that slows down the degeneration process and activates cartilage self-repair. The treatment exploits insulin-like growth factor-1 (IGF-1), which regulates somatic growth and has a central role in skeletal growth, and its mediator the growth hormone (GH). “Our drug candidate, REG-O3, is a peptide that promotes cartilage regeneration, enhancing mobility and reducing pain,” explains Christelle Vêtu, project coordinator and co-founder of Regulaxis. REG-O3 is a breakthrough hormone antagonist developed by Regulaxis. The drug has been designed to regulate the effect of the GH/IGF-1 axis on metabolism and promote GH-dependent cell growth. In addition, it supports cell differentiation through somatostatin, achieving an improved balance between proliferation and differentiation depending on cell needs. “Our peptide preserves the homeostasis of the environment of cells and helps adapt to its needs and activating the self-repair of tissues with the aim of halting OA,” emphasises Vêtu. Previous preclinical work by the RHYP scientists in animal models had shown that injection of REG-O3 directly into the knee of animals with OA improved regeneration of the cartilage and the surrounding tissues of the joint. Moreover, it decreased inflammation and, therefore, pain. Pharmacodynamic, pharmacokinetic and toxicologic evaluation of the drug in animal models validated its safety.
Clinical and societal impact of REG-O3
Gonarthrosis poses a significant socioeconomic burden with a concomitant reduction in productivity as patients have to leave work for prolonged periods of time. It also affects their everyday activities and impacts their quality of life and that of their families. Undoubtedly, there is a high unmet need for effective treatments against gonarthrosis capable of halting disease progression and promoting cartilage regeneration. REG-O3 constitutes a promising gonarthrosis-modifying drug that is safe to use and has fewer side effects than non-steroid anti-inflammatory drugs or other analgesics. Importantly, it is expected to require only a few injections as it has a long-term effect. RHYP successfully translated REG-O3 production to industrial scale under good manufacturing process conditions. Drug batches are now ready to begin clinical safety and efficacy screening in humans. With regulatory approval by the European Medicines Agency underway, REG-O3 has undergone further development optimisation, including a new formulation suitable for injection into the knee and a finalised protocol for administration in clinical trials.
RHYP, cartilage, OA, REG-O3, regeneration, knee, osteoarthritis, gonarthrosis