Osteoarthritis is the most common form of joint disease and affects some 30 million people in the US alone1) and an estimated 240 million people worldwide. MIV-711 has the potential of becoming the first drug to slow, stop or even reverse the progression of osteoarthritis.
Up to 40 percent of the population over 65 suffer from osteoarthritis (OA), characterized by pain and varying degrees of inflammation in one or more joints, mainly knees, hips and hands. Osteoarthritis in weight-bearing joints, like knees and hips, induces an increasing level of pain and decreased mobility for the patient, and may eventually result in joint replacement surgery.
Drugs capable of slowing, stopping or even reversing the progression of the disease are referred to as Disease Modifying Osteoarthritis Drugs. There is currently no such therapy approved for osteoarthritis and current treatments affect only day to day symptoms without affecting degenerative changes in the diseased joint.1) Standard of care is based on changes in life style and the use of analgesics. The long-term use of analgesics by osteoarthritis patients is associated with an increased risk of side effects such as gastrointestinal bleeding and opioid dependency.
Recent scientific work suggests that two processes – increased bone turnover and cartilage degradation – are involved in the development and progression of OA. Treatments that target both bone resorption and cartilage degradation may have an improved chance to demonstrate a clinical effect.
Through its targeting of both bone resorption and cartilage degradation MIV-711 has a unique potential to be the first disease-modifying treatment for OA. It is administered orally once daily, making it convenient for patients.
Cathepsin K is a protease that breaks down collagen, a protein that plays an important role in the structural integrity of both bone and cartilage. Medivir’s research in preclinical models has demonstrated that inhibition of cathepsin K can reduce the rate of joint destruction of osteoarthritis, and these findings have now been supported in clinical studies.
In September 2017, Medivir presented topline data after six months of treatment with two doses of MIV-711 in patients with moderate knee osteoarthritis. The results showed positive effects on both bone and cartilage. A further six months of treatment in a phase II extension study demonstrated an acceptable safety and tolerability profile, which was the primary objective of the study.
In addition, the patient group treated with 200 mg of MIV-711 for 6 + 6 months retained the response level of the positive signals for self-reported pain as well as other clinical symptoms identified in the initial phase II study. Treatment with MIV-711 for a total of 12 months provided ongoing treatment effects on the joint bone area growth and prevention of cartilage degradation in the affected knee.
Additional data showing disease-modifying properties in joint structures in patients with moderate knee arthritis already after 6 months, were presented at the American College of Rheumatology (ACR) in October 2018. In May 2019 new data from the six months’ open label extension study of MIV-711 in patients with osteoarthritis were presented as a poster during the Osteoarthritis Research Society International (OARSI) world Congress.
In August, the FDA published new preliminary guidance for the development of disease-modifying treatments for osteoarthritis. The FDA modified its previous approach to structural end-points and the new guidance discuss structural impact as treatment goals in clinical studies and how it could potentially be used for so-called ”accelerated approval”. MIV-711 has already been granted Fast Track designation as a disease-modifying agent for osteoarthritis.
Phase II data provides good support for further clinical development of MIV-711 as a disease-modifying treatment for osteoarthritis. The recent published data in “Annals of Internal Medicine” from the MIV-711 phase II study have shown a significant reduction in bone and cartilage progression with an acceptable safety profile. Link to the article in the journal Annals of Internal Medicine.
Medivir continues to aim to establish a license or collaboration agreement for MIV-711.