An increasing number of patients here are trying to obtain Invossa-K, an osteoarthritis treatment by Kolon Pharma which doctors began to prescribe this month. Even some foreign patients are coming to Korea to have the injections of this medicine.
Invossa, the first genetic therapy of knee osteoarthritis in the world developed by Kolon Life Science, has proved its efficacy in easing pain and improve the function for two years or longer with just one injection in knee joint cavity. In particular, the two major clinical trials conducted in the United States received attention by confirming its effects in regenerating cartilage. Currently, Kolon Life Science is continuing to develop it to win approval as a Disease Modifying Osteoarthritis Drug (DMOAD).
In Korea, however, the drug has got approval only for the indication of pain improvement and not for improvement in the structure of cartilage. It is also more expensive than the existing treatments.
There are both expectations and concerns about the domestically created genetic osteoarthritis treatment. Korea Biomedical Review met with Professor Yoo Jae-doo of Ewha Womans University Mokdong Hospital, who has taken part in the domestic clinical trials of Invossa, to hear about the therapeutic aim of osteoarthritis and Invossa’s curative effects.
Question: We heard that there a growing number people with secondary osteoarthritis caused by excessive exercise in addition to primary osteoarthritis resulting from population aging.
|Professor Yoo Jae-doo of Ewha Womans University Mokdong Hospital talks about the effects Insossa has on treating osteoarthritis, during a recent interview with Korea Biomedical Review.|
Answer: Osteoarthritis is caused by wearing out of cartilage which leads to the inflammation of the joint or by the destruction of cartilage resulting in pain or deformation of joints. In addition to the primary degenerative osteoarthritis mainly occurring in seniors, there is a growing number of secondary osteoarthritis caused by ligament damage resulting from excessive exercise. The first case of degenerative osteoarthritis can be found commonly from senior citizens while the second example can be found mainly among young patients.
Q: Treatment for arthritis is known to be complicated. Why is that?
A: That is because there still is no way of returning the cartilage to normalcy. Unlike other tissues, cartilage cannot restore itself after injury. Although there is a close approach to treatment, it is limited and so doctors treat the disease with surgery.
Q: What is the aim of treating osteoarthritis patients, then?
A: Osteoarthritis patients’ ligaments and muscles become weak and contracted. They also complain of pain because of the inflammation of the Synovial membranes. Therefore, the first objective of treating osteoarthritis patients is to reduce their pain. Also, we make efforts to delay surgeries for replacing joints with artificial ones as long as possible. The artificial joint’s lifespan is about 15 years, but the average life expectancy has also increased. That is why 85 to 90 percent of patients receiving artificial cartilage have to go through reoperations.
It is best for patients to delay surgery. Thus, we reduce the patient's discomfort through easing their pain but the disease progresses. Drug use also requires a lot of attention due to side effects on the gastrointestinal tract and cerebrovascular systems. Therefore doctors had wished to have other treatment options with fewer side effects.
Furthermore, it is necessary to reduce the secondary deformation, including the injury or loss of cartilage, but there is no remedy yet to reduce these secondary transformations.
Q: Currently, the ways of treating osteoarthritis patients’ are to give them pain relievers, injection therapies or artificial joint replacement. What treatments do doctors need most in the clinical field?
A: We need drugs or injections fewer side effects most, and medicines that can reduce pain for a long time. The existing medications are insufficient regarding effects that can sustain for a long time. Currently, there are oral medications, hyaluronic acid, and steroid injections.
Pills can cause pain if you stop taking them, and steroids, which are used in the case of severe acute pains, can result in various adverse effects and have quite limited options. Hyaluronic acid has been approved to be re-administered every six months. There are relatively few choices. We need more diverse options.
Q: The recent approval of Invcossa has attracted attention from medical workers and patients. We heard that you participated in the clinical trial of this medicine.
A: Among the Kellgren Lawrence 3rd grade patients, we selected those with less than 6 square centimeters of cartilage loss and with less severe joint deterioration as the subjects of the study.
Q: How soon do patients feel their pain eased after the administration of Invossa?
A: We checked them in the first, third, sixth and 12th month, and patients usually replied they experienced pain relief effects from the third month. In the sixth month, 84 percent of the patients felt significant pain relief effects. And there were no additional treatments during the period.
The clinical trials’ parameters were VAS (Visual Analog Scale for Pain), IKDC (International Knee Documentation Committee)’s knee function evaluation, and WOMAC (Western Ontario and McMaster Universities Osteoarthritis) index, a set of standardized questionnaires to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints. This just means that those patients who could feel pain relief effects could also lead a life without inconvenience resulting from pain. These patients improved so much that they didn’t need any other additional drugs.
Q: Invossa has won approval to improve pain and joint functions in Korea. The clinical trials found it had improved the joints’ structure after 10 months of the administration, but failed to receive regulators’ recognition for the indication of improving cartilage structure. Do you believe that future clinical trials will prove its effects on improving cartilage structure?
A: In the U.S. clinical trials, 80 to 85 percent of patients stated that they had experienced pain relief effects for two years after taking Invossa. Although the numbers were small, some patients even showed improvement of the structure in the cartilage. Once released on the market, we expect to see positive results after patients use it for three years or longer.
Q: In Korea, the clinical trial period is rather short lasting for just a year. How long are further observations scheduled for?
A: It is for more than 10 years. A study is going on in the U.S. with a larger group of patients and for a more extended period. After confirming the data later, we expect to be able to supplement the drug regarding its safety and effectiveness.
Q: There are controversies over the cost. It cost nearly 6 million won for one administration, causing criticism it is too expensive. What is your opinion on this matter as a person who conducted clinical trials?
A: It is true that prices are burdensome. However, you should not regard it as expensive, considering outpatients’ medical costs and time as well as social and economic costs, direct and indirect, resulting from adverse drug reactions. Patients with old age or associated diseases can only receive treatments through medications. However, patients who have to resort to physical therapy and cannot receive medication treatment for fear of secondary side effects also complain about financial burdens.
As Invossa can improve pain for two years with just one administration, it can of help for elderly patients, patients who cannot go through artificial joint replacement surgery, those who suffer from pain, and those with associated diseases.
Q: The method is a direct injection into glenoid cavity. Are there any concerns about other synovial membrane irritations?
A: Generally, all intraarticular injections can cause hypersensitivity to the synovial cavity. This can also occur in hyaluronic acid or steroids. For Invossa, there was a case where it showed adverse side effect due to the specific person’s genetic makeup, but it gradually improved over time. Invossa is highly recommended because it does not require repeated administration in short intervals but has to be taken just once. Nevertheless, it is safe to take a rest at the hospital before leaving it.
Q: What is the biggest difference between stem cell therapy and Invossa?
A: Currently, the biggest difference is the stem cell therapy requires surgery while Invossa does not. Stem cells therapy has also failed to prove effects on improving cartilage or its structure in the long term and is still in the follow-up process.
Q: The dosage used in the U.S. clinical study is different from the amount of dosage used in Korean studies. Is there any possibility that the difference in dosage will affect the improvement of joint structure or duration of pain relief?
A: No there isn’t. The difference was caused by the difference in production in Korea and the United States. In the clinical fields, the difference is negligible.
Q: What can we expect in the future clinical trials?
A: Patients will be monitored for five years and then monitored for more than 10 years. As I know, the company is planning clinical trials to expand indications for K&L2 cases and re-administering it for them.
Q: We have heard many patients outside of Korea want to take Invossa.
A: There are many foreign patients at our hospital waiting to take it
Q: What do you expect further in the future or existing treatments of osteoarthritis?
A: Most of all, osteoarthritis treatments should be focused on relieving pain because the worst thing for patients is feeling the pain. Next, I hope there will be effects on improving the structure of cartilage and joints regardless of the forms of treatment.
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