MIV-711 introduced in this episode is an anti-osteoarthritis project from a Swedish company named Medivir. The candidate slows or reverses the progressive degeneration of joints caused by osteoarthritis through inhibiting proteinase K. The project is currently in Phase II clinical trial. Why we chose this project as the topic of this program? Firstly, there are really not ideal OA treatment drugs on the market, and DMOAD drugs are very popular; secondly I have done research in this field and familiar with it, therefore I pay more attention to this project.
Osteoarthritis is a relatively popular chronic joint disease, with an incidence rate of 80% and a disability rate of over 50% among people over the age of 60 in China. And it caused a heavy burden to the society. The current treatment of osteoarthritis is maily pain relief and increased lubrication, but this kinds of treatment cannot inhibit the further deterioration of joint structure. After 5 to 10 years of disease progression, patients with advanced OA can only take joint replacement, surgery for irreversible treatment. There is currently no effective treatment for that 5 to 10 years of disease progression.
There are many OA treatment projects currently under development, but people pay more attention to projects that can act on both symptoms and structure, by rebuilding and repairing damaged cartilage to release symptoms, delay joint aging, and delay surgical replacement. The results of the clinical phase II trial showed that compared with the placebo group, Sprifermin can significantly improve cartilage thickness and significantly reduce the pain of patients.
In addition to Sprifermin, other DMOAD drugs under research have also made good progress, including the project MIV-711 introduced in this Episode. An article published in Clinical and Experimental Rheumatology in February this year showed that in the pain-predominant subgroup of the unilateral knee joint, MIV-711 treatment was found to significantly reduce OA pain with a beneficial structural effect.
Cathepsin K is a protease that breaks down collagen, a protein that plays an important role in the structural integrity of bone and cartilage. Preclinical studies have shown that MIV-711, as a cathepsin K inhibitor, is beneficial to both bone and cartilage, and can reduce the joint destruction rate of osteoarthritis by inhibiting cathepsin K. In September 2017, Medivir tested positive effects on bone and cartilage in patients with moderate knee osteoarthritis after receiving MIV-711 for 6 months. An additional 6 months of treatment in the Phase II extension study validated its safety and tolerability, meeting the primary clinical endpoint of the drug study. Experimental results demonstrate that treatment with MIV-711 for a total of 12 months provides a sustained therapeutic effect on the growth of the articular bone area and the prevention of cartilage degeneration in the affected knee joint.
【Advantages and Challenges】
Advantage
1. The OA market is huge
The incidence rate of people over 60 years old in China is as high as 80%, and the disability rate exceeds 50%. According to the statistics of country's seventh census, China has a population of over 260 million people aged 60 and over, with a huge population base, and with the population aging, this market is also showing an upward trend.
2. Unmet medical needs
The current treatment methods for osteoarthritis are pain relief and increased lubrication, which cannot inhibit the further deterioration of the joint structure. Patients with severe OA can only choose surgery such as joint replacement. As OA patients gradually become younger, some patients may still face with the problem of replacing joints, both financially and physically, it is a heavy burden.
3. Oral therapy, high compliance
The DMOAD projects under study, including Sprifermin, are all injected into the knee joint. Although the trouble of long-term administration is reduced, the knee joint injection still has certain fears for ordinary patients. Because MIV-711 is taken orally, at least for some patients, it greatly improves their compliance.
Challenge
1. Clinical evaluation is not easy to complete
On one hand, it is the pain indicator, which is a highly subjective indicator. Different people have different degrees of sensitivity to pain, so the placebo effect in general pain experiments is very strong. If the sample size is small, it is hard to distinguish. On the other hand, the change of bone structure is not easy to observe. I used to study Sprifermin. The change of cartilage before and after treatment is very small. It usually takes 6 to 9 months. It can only be judged by standard SOP, because MIV-711 is cathepsin K inhibitor, which does not act only on cartilage, so the situation may be better, but it is still not easy.
2. Long clinical trial cycle
Because of the changes in the clinical key bone structure set by the project, and this change will not be short to the extent that it can be detected by NMR, MIV-711 is set to 6 months, and in some experiments, there is an extended observation of 6 months after 6 months, and due to the difficulty of judgment due to small changes, the number of cases should be large, which increases the time required for enrollment.
3. Security requirements
On one hand, this requires long-term administration, and most of the patients are elderly, and their health is generally not very good. Many are still taking various other drugs, which is likely to cause cross-reaction between drugs and affect safety observation. On the other hand, Merck's odanatinib was also a cathepsin K inhibitor, but due to cardiovascular adverse reaction, although its study has lasted 12 years and 16,000 patients were included, it has still not been approved. There are different explanations for the failure of odanatinib, but with this foreshadowing, special attention is still needed during research.
The above is the entire content of our current episode of "Doctor Wang Medtech". Orthopedics is a good direction. At present, there are many instruments in the field of orthopedics, but there are few drugs. There is a lot of room for development in the future. When encountering some major orthopaedic projects separated by big pharmas, it is usually difficult to hold them,because they requires enterprises to have considerable strength in clinical and medical fields.
In the third season, we will continue sharing some orthopaedic projects. We hope that our third season can give audiences a better experience. You are also warmly welcomed to give us your needs and suggestions to help us promote this program. Finally, thank you a lot for your support, we will see you in the third season.
