K-134
| Kowa Company, Ltd. reviewed comprehensively the results of phase 2b trial and the obtained findings so far. As a result, we heard that Kowa had decided cancellation of the development of K-134 which was targeted arteriosclerosis obliterans. Regarding the indications other than arteriosclerosis obliterans,it has been studied by Kowa.
The following is the content that we have been developing arteriosclerosis obliterans as an indication until now. |
| Target disease | Arteriosclerosis obliterans |
|---|---|
| Development stage | Completed phase IIb trial in Japan |
| License out to | Kowa Company, Ltd. |
| Overview | The product is being developed as an antiplatelet agent to improve arteriosclerosis obliterans which is arteriosclerosis in legs. Among arteriosclerosis obliterans, the drug is particularly for intermittent claudication in Stage 2 (See Diagram: Symptoms of Arteriosclerosis Obliterans below). As a result of the past research and development activities this development product has been confirmed to: （1）Have an antiplatelet aggregation action; （2）Have an intimal hypertrophy inhibitory action; and （3）Not encourage hemorrhage. In 2011 phase II clinical studies were completed in the US and Japan in which improved walking was verified in patients having the symptom of intermittent claudication associated with arteriosclerosis obliterans. |
Development Progress
| 2002 | Sep. | Licensed all worldwide rights to Kowa Company, Ltd. |
|---|---|---|
| 2006 | Apr. | Initiated phase I trial in Japan |
| 2007 | Oct. | Completed phase I trial in Japan |
| 2008 | Jul. | Initiated phase IIa trial in Japan |
| 2011 | Jan. | Completed phase IIa trial in U.S. |
| 2012 | Jan. | Initiated phase IIb trial in Japan |
| 2014 | Dec. | Completed phase IIb trial in Japan |
Action Mechanism of K-134
The Drug-Western method has proved that K-134 is a strong PDE inhibitor and is bound to CD36, a platelet collagen receptor and cofilin, a cytoskeletal protein present in platelet and vascular walls. Because none of the existing commercial antiplatelet drugs binds to these two target proteins (CD36 and cofilin), this development product is considered to have a new action mechanism which differs from existing antiplatelet agents having PDE inhibitory action.
Platelet Pattern Diagram
Symptoms of Arteriosclerosis Obliterans
Arteriosclerosis obliterans is classified into Stage 1 to Stage 4 and progression of the disease may lead to amputation of a leg. Once arteriosclerosis obliterans develops, arterial sclerosis is likely to be progressed in other vessels (brain, heart, etc.)
| Stage 1 | Numbness, feeling cold | Numbness and/or feeling cold occur due to impaired blood flow to the lower limb caused by arterial sclerosis immediately after abrupt exercise or continuous walking. In most cases, the symptom disappears immediately and usually there is no symptom. |
|---|---|---|
| Stage 2 | Intermittent claudication | Pain or stiffness in the muscle is triggered by walking for a certain distance, leading inability to walk, but this is relieved by rest for a while. |
| Stage 3 | Pain at rest | Inability to supply sufficient blood flow to the lower limb even at rest causes pain. |
| Stage 4 | Ulcer, necrosis | Skin necrosis or ulcer develops starting from the impaired blood flow. |
Mechanism of Development of Arterial Sclerosis
Vessel Pattern Diagram
336KB（Enlarge the above diagram）
Normal condition
A vascular endothelial cell has the function of preventing the blood from clogging and usually blood flows smoothly to transport oxygen and nutrients throughout the body.
When a vessel gets damaged
When a vessel is strained by cholesterol or some other factor and gets damaged, platelets clump together to block the scar. Platelet clump adhered to the vessel wall makes the vessel wall thicker, losing the resilience of the artery and making the artery harder. This is the beginning of arterial sclerosis. As a result, the blood path gets thinner and blood is apt to get clogged, failing to deliver sufficient oxygen and nutrients throughout the body. Clogged vessel triggers thrombosis, Myocardial infarction, cerebral infarction, etc. 。
Liberation of part of a blood clot
When part of platelet clumps is liberated and flows out, this may go into a thin vessel and get clogged, triggering thrombosis, Myocardial infarction, cerebral infarction, etc.
